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Human Anatomy
Questions Alerts!
Common questions in pharmacy exam is to ask!
This chapter reviews essentials and definitions of systemic human anatomy terminology and provide a basic understanding of how
the human body is structured with emphasis on clinical applications. This chapter also reviews cellular mechanism in human
physiology.Body Movements
· Q. Abduction: Movement away from the midline of the body.
· Q. Adduction: Movement toward the midline of the body.
· Extension: Lengthening or straightening of a flexed limb. Extensor refers to movement in the posterior
direction. For example, when standing up knees are extended.
· Flexion: Bending of a part of the body.
· Dorsiflexion: Backward (upward) bending of the foot.
· Plantar flexion: Bending of the sole of the foot downward toward the ground.
· Pronation: Act of turning the hand so that the palm faces downward.
· Q. Supination: Act of turning the hand so that the palm is uppermost.
· Eversion: Outward turning.
· Fascia: Fibrous membrane separating and enveloping muscles.
· Anterior (ventral): Front side of the body (example: Abdomen is anterior to the spinal cord).
· Posterior (dorsal): Back of the body (example. Spinal cord is posterior to the stomach).
· Q. Lateral view: from the side of the body.
· Q. Medial view: from the middle of body (between two legs).
· Deep: Away from the surface.
· Superficial: On the surface (example. Superficial veins can be viewed through skin).
Distal: Far from the point of attachment to the trunk or from the beginning of a structure (Example. The distal end of the stomach
is at the small intestine).
Inferior: Below another structure. Caudal (pertaining to the head) means inferior in human. (Example; The urinary bladder lies
inferior to the kidney).
Body Cavities
A body cavity is a fluid-filled spaces in the body that holds and protect internal organs. There are two largest cavities includes
dorsal cavity and ventral cavity.
Dorsal (posterior) cavity
The dorsal cavity is at posterior and consist of sub cavities cranial and spinal cavities.
Q. Cranial: Brain, vertebral cavity (or canal) that contain spinal cord. These two cavities are continuous and covered by
meninges.
Ventral (anterior) cavity
The ventral cavity is at the anterior or front of the trunk. This includes three sub cavities includes thoracic, abdominal and
pelvic.
Right upper Left upper Thoracic cavity: Lungs are pleural cavities and heart is in
Gallbladder, pancreas Q. Spleen pericardial cavity.
Q. Abdominal cavity: Abdominal cavity is consisting of by
Right lower Left lower
ribcage and pelvis which contains the kidneys ureters, stomach,
Appendix Sigmoid colon
liver, gallbladder and pancreas.
Kidney Kidney Q. Pelvic cavity: Consist reproductive organ, urinary bladder,
pelvic colon (sigmoid colon) and rectum or anus.
Opposite opposite
Abduction Adduction
Extension Flexion
Lateral Medial
Dorsal Ventral
Proximal Distal
Prone Supine
Types of Functions
muscles
Q Skeletal Muscle attached to
muscle skeleton tendons,
bones; Voluntary.
Q. Smooth Muscle of organs,
muscle stomach, and blood
vessels muscle:
Involuntary.
Q Cardiac Heart muscle:
muscle Involuntary
Anatomical Planes
· Q. Sagittal plane: Plane created by an imaginary line that is parallel to the median plane. Separates the body into right and
left portions.
· Midsagittal plane (median plane): Plane created by an imaginary line that divides the body into right and left halves.
Separates the body/body part into equal right/left portions.
· Parasagittal plane: Divides the body into unequal right and left portions.
· Coronal plane/frontal. Divides the body/body part into anterior and posterior portions.
· Transverse plane/horizontal: Divides the body/body part into superior and inferior portions.
· Oblique plane: Passes through the body/body part at an angle. Postural: Positions such as standing, sitting, lying down,
turning right or left.
Q. Orthostatic: Standing upright and lying down supine.
Fowler’s position: Seated position with back support (head elevated).
Trendelenburg position: Sleeping position with feet elevated and head lowered.
Sits hunched forward: Tightening chest muscle.
QAlerts!
Anterior cruciate ligament is present in? Knee
Muscles
Body is made of three types of muscle tissues:
Skeletal muscles
Abduction → (25)
Flexor muscles are present in→ (10;pull joints toward middle line)
Extensor muscles are present in→ (11;push joints away from middle line)
Separates the body into unequal right and left portions (6)
Separates the body into equal right and left portions (8)
What protects from injuries in the front of the knee joint (9)
What muscles are found in limbs, foot, arms (flexor and extensor)
The shoulder joint are type of? Ball and socket joints
Popliteal space? A lozenges shape space in knee joint also called popliteal fossa.
What is the other name of hip joint, shoulder joint? Ball and socket.
Example of the carpals in the wrist? Scaphoid, lunate, triquetral, hamate, pisiform, capitate, trapezoid and trapezium
Questions Alerts!
Common questions in pharmacy exam is to ask!
Stomach secretions (intrinsic factor, HCL, gastrin). Pepsin is digestive enzyme present in GIT break downs
proteins.
Role of small intestine in absorption of nutrients, drugs and supplements.
Large intestine (colon) bacteria and excessive absorption of water that cause constipation.
Disease of GI system like dyspepsia, GERD, peptic ulcers, Crohn's disease, ulcerative colitis and irritable
bowel syndrome (IBS) symptoms.
Digestive enzymes, and pancreatic enzymes.
This chapter review anatomy, physiology and pathophysiology of the gastrointestinal system, common disease that
occurs in gastrointestinal tract.
Mouth
· Tongue has bony attachments (styloid process, hyoid bone) attached to the floor of the mouth by frenulum.
· Posterior exit from mouth guarded by a ring of palatine/lingual tonsils.
· Ducted salivary glands open at various points into the mouth. This process involves teeth muscles of mastication move jaws and
tongue extrinsic and intrinsic muscles.
· Saliva amylase does hydrolysis of starch and glycogen into maltose.
ESOPHAGUS
· The esophagus is about 10" long.
· Food moves through esophagus by peristalsis.
· Cardio esophageal sphincter guarding entrance from esophagus.
· Pyloric sphincter guarding the outlet is much better defined.
· Fundus, body and pylorus recognized as distinct regions.
· Surface area increased by rugae, which serves as temporary store for food.
· Stomach secretes both acid and mucus (for self-protection).
STOMACH (pH 1.5 -3.5)
CHLORHYDRIC ACHLORHYDRIC Stomach Functions
layers
EXCESSIVE HCL IN LOW HCL IN
Mucosa Top layer releases mucous which consist
STOMACH STOMACH
of bicarbonate that protect gastric lining from acid.
Mucosa layer has gastric pits which
Infants Elderly contains parietal cells, chief cells, and G-cells.
Submucosa Contain connective tissues, nerve and blood vessels.
Higher absorption in acidic
Muscularis It made of 3 smooth muscle layers and helps
stomach: á PPI, H 2RA,
externa stomach peristalsis movement to get food down to
CaCO 3 Ketoconazole,
small intestines.
Serosa Outer layer contains tissues connecting to organs.
Low pH High pH
*Deficiency of intrinsic factors causes a type megaloblastic anemia i.e. pernicious anemia.
In the parietal cells CO 2 and H2 O are converted H + and HCO3 - catalyzed by carbonic anhydrase. The parietal cells
secrete HCl into the lumen of the stomach and concurrently absorb HCO 3- into the blood stream.
Gastric acid stimulations: Gastric acid production is stimulated by three mechanisms.
Vagal stimulation; Vagal nerve innervates parietal cells and stimulates H+ secretion directly.
Histamine release; Histamine is released from mast cells in the gastric mucosa and diffuses to nearby parietal cells.
Gastrin: It is released in response to eating a meal (protein), thus stimulates parietal cells to secrete H+.
Q Alerts!
What enzymes are released into small intestines? Pancreatic and bile secretions.
1) Intrinsic factor secreted from parietal cells deficiency cause? Vitamin B12
2) Pernicious anemia should be treated by parenteral (SC/IM) vitamin B 12.
3) Elderly persons have deficiency of vitamin? B12
4) Gastrin is secreted from pyloric gland of stomach.
5) What are stomach secretions occur in response to protein diet? Gastrin and pepsin.
A patient with ileostomy, what oral dosage is NOT suitable? Oral drugs especially sustain release (SR, CR, MR, CD) dosage
form.
Gastric Emptying Time
The caudad region of stomach contract to propel food into the duodenum. The rate of gastric emptying time is fastest if gastric
content is isotonic. Fat inhibits gastric emptying time (i.e. increase gastric emptying time).
Stomach → (Pyloric sphincter) → Duodenum
**
Factors promote stomach emptying Factors Inhibit gastric emptying
Gastric volume or increase Duodenal distention,
food volume in stomach High intensity, intermittent exercise
promotes gastric emptying. can slow gastric emptying.
Clear liquids empty rapidly than Fats and proteins breakdown in
solid food. small intestine.
Protein empty fastest than Temperature cold liquids (4 ˚C)
carbohydrate and then fats. empty slowly
Prokinetic drugs: Metoclopramide, domperidone used as antiemetics.
GLP-1 analog Liraglutide delay gastric emptying time cause weight loss side effects.
Gastric Transit Time
The time required for ingested food to pass through the GI tract. Shorter transit time is seen in conditions associated
with gut hypermotility such as diarrhea. Delayed passage from any cause results in a longer transit time.
Gastric á transit time Gastric â Transit time
Constipation Diarrhea
Large Intestines
It is also known as colon.
· Highest basic or pH (varies between 5.5 to 7).
· The large intestine reabsorbs water then eliminates drier residues as feces.
· Colon consists of higher flora and fauna in GI tract Q. 90 to 99% anaerobic bacteria. Example B. fragilis and C.
difficle anaerobic and aerobic E. coli.
· Q. Colon bacterial produce vitamin K 2 (menaquinone).
QAlerts!
Most common bacterial found in colon? 99% anaerobic bacteria
Colon bacteria produce? Menaquinone.
Diseases of the gastrointestinal system
Diseases of the Mouth and Jaw
· Oral thrush is caused by Candida albicans, and moniliasis.
· Gingivitis (gum inflammation) or gingival hyperplasia is caused by Fusobacterium sp.
· Stomatitis is Inflammation of mouth cavity. Herpes stomatitis caused by herpes infection, and aphthous stomatitis caused by
oral hygiene or damage to mucus membrane.
· Mucositis: Oral ulcers also known as canker sores or aphthous ulcers.
Disease of the Salivary Glands: Sjogren syndrome (dry mouth, dry eyes) is autoimmune disease. It is associated with rheumatoid
arthritis.
Sialorrhea is an excessive secretion of saliva in infants, children, Parkinson’s disease can cause by mucosal irritation.
Medications associated mouth/jaw side effects
· Cholinergic drugs cause hypersalivation.
· Anticholinergics cause dry mouth
Diseases of the stomach
Dyspepsia
Defined as pain or discomfort in the upper abdomen. Symptoms are nausea, fullness, early satiety, bloating or regurgitation. The
dyspepsia could be due to esophagitis, GERD (Also referred as heartburn or regurgitation), peptic ulcer (GU or DU) 15-
25%, Reflux esophagitis, 5-15%, gastric or esophageal cancer (<2%).
.
Peptic Ulcers Disease
Gastric acid induced (damage in stomach surface mucus, decrease in bicarbonate secretion, decrease in mucosal blood flow, and
decrease in epithelial cell capacity).
Types of peptic ulcers esophageal, gastric ulcer, duodenal ulcers.
There are two main causes of peptic ulcers H. pylori, and NSAIDs induced ulcers. Ulcers forms due to increase in stomach acid
& pepsin and decrease in defence of stomach against acid protection.
Peptic ulcer disease is ulcer formation in the upper gastrointestinal tract this includes gastric ulcers occurs in stomach linings,
duodenal ulcers in small intestine.
Aggravating causes: H. pylori, NSAIDs, ASA, cigarettes, alcohol, impaired regulation of acid-pepsin secretion.
There are two main causes peptic ulcer of Helicobacter pylori infections or drug induced (NSAIDS).
Standard diagnostic tests: Endoscopy and urea breathe test (UBT) for H. pylori. Fecal occult blood test (FOBT).
H. pylori ulcers NSAID induce ulcers
Etiology H. pylori infections (gram -ve bacteria) NSAIDs
Diagnostic Urea Breath Test (UBT), Endoscopy Endoscopy
Treatment Quadruple therapy: amoxicillin +clarithromycin +metronidazole Stop NSAIDs
+ PPI for 14 days. or add Proton pump inhibitors.
Esophageal: associated with some drugs like bisphosphonates, and methotrexate.
· Duodenal ulcers are mainly caused by Helicobacter pylori and the second most common reason is medications like NSAIDs.
· Zollinger Ellison syndrome is tumor formation that cause excessive secretion of HCl.
· Gastritis (inflammation of gastric or stomach lining). Caused by NSAIDS, cigarette smoking, and heavy alcohol.
· Gastroenteritis: Inflammation of entire GI tract.
Diseases of the Small Intestine
Celiac disease
Celiac disease also known as celiac sprue or gluten intolerance.
Celiac disease is caused by sensitivity to gluten. Gluten is seed storage protein found in certain cereals and grains. It damages to
small intestine and cause inability to absorb gluten. This is due to inability of absorption of gluten (it mainly affects on upper part
of small intestine). Gluten is protein present in wheat, rye, barley, cereals. Most people have 1 or more symptoms and the
chronic diarrhea is the common symptom.
· Diagnosis, if blood test is positive then biopsy of small intestine.
· Management: only treatment is avoiding food containing gluten.
QAlerts!
Celiac disease is caused by? Gluten intolerance
Gluten is present in all foods, except? rice
Diseases of the Colon
Inflammatory bowel disease (IBD)
Autoimmune condition and can occur at any age however more common in young adults. Consist of two conditions, Crohn’s
disease and ulcerative colitis.
ULCERATIVE COLITIS CROHN'S DISEASE
Q. Localized to colon. Site of origin is rectum. Crohn's disease (small intestine and colon), chronic inflammatory of ileum, and
colon, this can lead to fistula. Skip patches are found entire GI system. Site of origin
is terminal ileum.
Fistula (ulcers in GI tissue) is present Crohn's.
Drug of choice 5-Aminosalicylic acid (5-ASA) 5ASA or Oral/iv prednisone
Fistula is treated by infliximab, adalimumab or metronidazole.
10-20 liquid stools per day containing blood and Less common liquid stools per day containing blood and mucus.
mucus.
Abdominal pain, diarrhea, blood in stools Crampy abdominal pain, diarrhea, blood in stools, weight loss (toxic megacolon).
(bloody diarrhea), weight loss.
Marked increase risk of colon cancer Slight increase risk of colon cancer.
Irritable Bowel Syndrome (IBS)
This can cause severe diarrhea, constipation, bloating and cramps, nausea and vomiting (No bleeding).
Bristol-stool Form Scale is used to determine severity of constipation (1 is constipation and 7 is diarrhea).
IBS-D predominant diarrhea: Antidiarrheals: Loperamide, Bismuth subsalicylate.
IBS-C predominant constipation: laxative: senna, bisacodyl, lactulose, PEG, psyllium
IBS-M mixed diarrhea and constipation (watery stools with pellets).
QAlerts!
What symptoms are NOT present in irritable bowel symptoms?
Clostridium difficile
Inflammation of colon due to overgrowth of Clostridium difficile a gram +ve anaerobic bacteria.
The most common cause of infectious diarrhea and responsible for 20-30% of antibiotic associated diarrhea side effect. Most
commonly risk factor for older age >65-year-old, hospitalization and duration of hospitalization, single dose to longer duration of
antibiotic use. Hospitalized patients or recent antibiotic use patients are commonly affected by exposure to C.
difficile contaminated hands and environment Q. C. diff is contagious.
Q.The highest risk is associated with clindamycin, also fluoroquinolone, cephalosporins, aztreonam and carbapenems.
The Clostridium difficile is an obligate gram +ve anaerobic bacteria over growth produce exotoxin cause diarrhea. C. difficile is
communicable disease. Q. The first line is vancomycin po and alternate is metronidazole po, or iv.
QAlerts!
The most common antibiotics known to cause C. diff diarrhea is? Clindamycin
First line antibiotic therapy for C. diff diarrhea? Vancomycin oral
Hernia
A perturbation of GI tract or part of an organ through the body wall.
TYPES OF HERNIA
Inguinal Near the opening of the inguinal canal
(near pelvic). Q. More common in
elderly
Femoral Occurs in the femoral canal
Umbilical Occurs at Navel (umbilical card area)
Incisional Occurs at site of previous surgical
incision.
Diaphragmatic Upper abdomen at midline
(epigastric)
Hiatal hernia Q. Occurs when part of the stomach
pushes up through the diaphragm into
chest.
Upper GI bleeding
Peptic ulcers, duodenal ulcers, gastritis, duodenitis, Q. esophageal varices, gastrointestinal malignancy and esophageal ulcer.
Symptoms: dark, tarry stools or vomiting blood like coffee ground.
Q.Drugs that increase risk for upper GI bleeding: NSAIDs, ASA, corticosteroids, anticoagulants, aldosterone antagonist
(spironolactone), COX-II inhibitors, and SSRIs. If these drugs administered in combination risk would expect to additive bleeding
risk.
Lower GI bleeding
Hemorrhoids, inflammatory bowel disease (Crohn’s or colitis), NSAIDs induced bleeding, diverticulosis. Infectious
colitis, Q. colorectal varices and ischemic colitis.
Hemorrhoids: Small amounts of blood, mostly on toilet paper.
Variceal bleeding
The major cause of variceal bleeding is liver cirrhosis, portal hypertension. It is medical emergence and require referral.
QAlerts!
What are the cause of variceal gastrointestinal bleeding? Liver cirrhosis
What is the treatment of variceal GI bleeding? Beta blockers
What is the cause peptic ulcers? NSAID or H. pylori
Digestion and Absorption
GI secretions include saliva, gastric secretions, pancreatic secretions and bile.
Digestive enzymes are classified based on their target substrates.
· Q. Proteases and peptidases split proteins into small peptides and amino acids.
· Lipases split fat into three fatty acids and a glycerol molecule.
· Carbohydrase’s split carbohydrates such as starch and sugars into simple sugars such as glucose.
· Nucleases split nucleic acids into nucleotides.
Enzymes Produced from Released into Function
Salivary amylase Salivary gland Mouth Polysaccharides (starch and
glycogen breakdown to maltose)
Maltase Small intestine Small intestine Maltose to 2 glucoses
Pancreatic enzyme
Pancreatic amylase Pancreas Small intestine Starch to glucose and fructose
Lipase Pancreas Small intestine Lipids (fats) to fatty acids
Proteases (Tripsinogen & Pancreas Small intestine Proteins to amino acids
chymotripsinogen)
QAlerts!
What are the function proteases? Breakdown proteins to amino acids
Maltase? Break maltose to 2 glucoses.
Carbohydrates digestion
The most common site of carbohydrate absorption is small intestine. Only monosaccharides such as glucose, fructose, and
galactose are absorbed.
Amylase: Hydrolyse starch and glycogen into maltose. There is amylase in saliva and stomach (STARCH & GLYCOGEN à MALTOSE).
· Q.Maltase: Converts maltose into glucose + glucose.
10. Alpha glucosidase 11. 95-100% anaerobic bacteria 12. Fructose + glucose
Questions Alerts!
Common questions in pharmacy exam is to ask!
· Central nervous system: What section of brain controls voluntary and involuntary movements?
· Blood brain barrier definition and functions. Cerebrospinal fluid.
· Peripheral nerves system: cranial nerve, peripheral nerves radial nerves, ulnar nerves. Sciatica.
· Types of Neurological disorders: Multiple sclerosis, chronic spasticity, Bell's Palsy, Neuralgia, Seizures or epilepsy, Fibromyalgia,
and Parkinson's disease.
Nervous system divided into central nervous system and peripheral nervous system. The central nervous system consists of
brain and spine.
Question Alerts!
1) Voluntary and involuntary movements are controlled by?
2) What section of brain coordination and control balance?
BRAIN
· Q. Largest section of brain and controls voluntary (c function: Think and decide what to say) and involuntary movements
(aognitive functions). utonomicCerebrum:
· Q. Controls balance (GAIT) and modifies body movements (motor) and maintain body coordination and balance.Cerebellum:
· Brain stem: Is the posterior part of the brain consisting of pons and Q. The medulla oblongata helps regulate breathing,
heart, and blood vessel function, digestion, and swallowing and sneezing.medulla oblongata and mid brain.
· Thalamus: affects sensory levels, awareness and alertness.
Q. Corpus Collosumof brain. connects and communicates between right and left hemisphere
· Spinal cord: Vertebral column, epidural space, meninges, spinal cord, dorsal vertebra, and spinal nerve.
QAlerts!
Corpus collosum relates to? Connects right and left hemisphere of brain
Cognitive functions of Alzheimer’s patients are controlled by? cerebrum
Medulla oblongata functions? Respiratory, cardiovascular, and digestion
What part of brain controls defecation? Medulla oblongata
FRONTAL LOBE
QMotor QCognitive. Behavior Arousal
Voluntary movements Memory Personality Attention
Planning, Initiation Problem solving Social and sexual
Frontal lobe
Spontaneity Judgment Impulse control
Motor, cognitive,
Language Abstract Mood and affect
behavioral and
Language expression Abstract thinking arousal. The limbic
Eye movement Executing functions. system or
Q. Mesolimbic
pathways are present
in just beneath the
TEMPORAL LOBE Auditory, speech, memory function, and retrieval. Q. Medulla cerebrum and both
oblongata: breathing, cardiovascular, digestion. sides of thalamus.
Wernicke’s area: In temporal lobe language comprehension.
OCCIPITAL LOBE Visual reception (optic nerve) and interpretation. QAlerts!
PARIETAL LOBE Processing sensory input, sensory discrimination, body orientation, Medulla oblongata is
somatic area. present in?
Mesolimbic pathways
(dopaminergic) are present in?
Meninges
· The meninges are three concentric membranes that surround and protect brain and spinal cord.
· The dura mater: outer most membrane.
· The arachnoid: middle layer, transparent, flexible
· The pia mater: inner layer is fine, and delicate.
· Epidural: Between the skull and the outer endosteal layer of the dura mater.
Brachial plexus
· Q. Ulnar nerve: Passes through the shoulder, elbow to wrist (motor functions finger abduction & adduction. Flexion of digits
4 & 5).
· Q. Radial nerve runs through forearm, wrist to finger thumb. It supplies to muscles of forearm.
· Q. Axillary nerve (circumflex): It supplies the deltoid and teres minor muscles, shoulder joint, and skin on back of arm.
· Median nerve: Thumb and index fingers.
BRACHIAL PLEXUS PERIPHERAL NERVE DAMAGE
Radial nerve damage cause Q. Elbow/Wrist drop
Ulnar nerve damage cause Q. Claw hand (small fingers hand contract)
Axillary nerve damage Shoulder (loss of sensation over the lower half of the deltoid.
Medial nerve damage Thumb and index fingers
mnemonic
QAlerts!
Which nerve plexus serves arm and shoulder nerves? Brachial
Radial nerve damage cause? Elbow & wrist
Sciatic nerve passes to? Thigh and lower limbs
Cranial nerve
12 CRANIAL NERVE: 10 out of 12 origins from brain or brainstem and spread to facial function. Functions
Olfactory For Smell Sensory
Q. Optic For vision sensory
Oculomotor For looking around: Eye upward, medial, downward movement.
Vestibular Trochlear For moving eye: Eye down and in movement sensory
Trigeminal For feeling touch on face, forehead and cheek, clench teeth. Q. CHEWING
Abducens To move eye muscles: Look side to side
Facial To smile, wink and help to taste for the anterior 2/3 of tongue.
Acoustic Hearing
Q. Glossopharyngeal For swallowing, gagging, posterior 1/3 of the tongue
Q. Vagus For swallowing, talking, defecation, slowed heart rate or Sensory & motor
PARASYMPATHETIC.
Spiral accessory shoulder shrug
Q. Hypoglossal Tongue movement
QAlerts!
Which cranial nerve is responsible for chewing motions? Trigeminal neuralgia
Optic nerve? A sensory nerve connects retina to the brain.
Vagus nerve is? A parasympathetic nerve
Motor muscle for mastication? Masseter muscle
Defecation controlled by? Vagus nerve
Question Alerts!
Myelin sheath damage (demyelination) and axon degeneration is associated with?
Multiple Sclerosis (MS)
Myelin sheath regenerates by oligodendrocyte (Shwann cells) and neural
stem/progenitor cells and pleotrophin.
Myelin sheath
Q. Shwann cells contain a lipid substance called myelin in their plasma membrane. When Shwann cell wrap around axon, a
myelin sheath forms. The autoimmune disease multiple sclerosis where the immune cells attack on central nervous system.
Multiple Sclerosis
The multiple sclerosis is characterized by destruction of myelin sheath (demyelination) and axonal degeneration & loss in
CNS. The MS is chronic and can be caused by autoimmune mediated action.
The main purpose of myelin sheath is to increase the speed at which impulses propagated along the myelinated fiber.
Treatment: Interferon’s beta, glatiramer acetate (Immunomodulators similar to interferon beta), mitoxantrone,
natalizumab, Q. Fingolimod (spingosine-1-phosphate receptor agonist), teriflunomide, and laqinimod.
QAlerts!
What cells generate myelin sheath? Shawnn cells.
Multiple sclerosis is degenerative disease caused by? Degeneration of myelin (demyelination)
What is dark granular inside cell body? Nissle substance
Vestibular system
Reflex adjustment of head, eyes and postural muscles provide a stable visual image and steady posture.
Functions of vestibular system balance, monitors changes of position of head. Coordination of eye movement with head, and
posture.
Nystagmus
Vestibular ocular reflexes. Q. Nystagmus. The direction of the nystagmus is defined as the direction of the fast (rapid eye)
movement. Therefore, the nystagmus occurs in the same direction as the head rotation. Normally initial rotation of the head
causes the eyes to move slowly in the opposite direction to maintain visual fixation.
Vertigo
Dizziness and false sensation of moving or spinning or object moving usually accompanied by nausea and loss of balance.
Treatment
Antihistamine: diphenhydramine, scopolamine. Benzodiazepines;
Calcium ion channel blockers: flunarizine
Meniere’s disease
Q. Meniere’s disease produces sudden episode attack of vertigo along with ringing in ears (tinnitus), dizziness, nausea and
progressive deafness. Attacks can last an average of 2 to 4 hours. Episodes can last from minutes to hours. Associated with
nausea and vomiting. Beta-histine is used for treatment.
QAlerts!
Nystagmus is? Rapid eye movement
Vertigo characteristic symptoms? False Sensation of moving
Meniere’s disease is treated by? Beta-histine
Temperature regulation
The homeostasis mechanisms regulate body temperature. Q.
When “Too COLD”: Heat is conserved by 1. Blood vessels constriction, 2. No sweating.
When “Too HOT” Heat given off by 1. Blood vessels dilations, 2. Sweating.
Sympathetic nervous system innervates heat loss by vasodilatation and sweat production.
Sympathetic nervous system innervates adrenal gland than increase metabolic rate.
Q. Thalamus in brain control homeostasis.
Thalamus à pituitary gland à thyroid à Increase metabolic rate.
Normal temperature (37.5 °C) or 99.5 °F
Q. Fever: >37.8 °C = 100.04 °F
High fever is defined >40.5 °C (104.9°F)
Hyperpyrexia (fever) = a fever >41.5 °C are rare.
Hyperthermia = >38.2 °C or 100.76 °F
Hypothermia = <35 °C, if <32 °C it can cause ventricular arrhythmias.
Heat stroke: Core body temp. >40.6 °C
QAlerts
High fever is defined as? >40.5 °C (104.9°F)
How to measure accurate core body temperature in infant and child? Rectal
Malignant hyperthermia
Malignant hyperthermia is rare genetic pharmacogenetics skeletal muscle disorder.
Q. Malignant hyperthermia can trigger by drugs that cause fever symptoms. E.g. Halothane, isoflurane and succinylcholine.
Q. Treatment: Dantrolene 2.5 mg/kg for Q5min. It works by reducing contractility.
QAlerts!
Example of drugs that cause malignant hyperthermia? halothane
What are the symptoms of neuroleptic malignant syndrome? High fever, muscle rigidity, cardiac arrhythmias
NMS is a medical emergence is treated by? Dantrolene IV
Febrile seizure
Q. Febrile seizure is due to the febrile response rarely exceeds 41–42°C. These seizures typically occur between ages 6 months to
5 years, with peak incidence between 9- and 20-month age. Associated with fever >38.2 °C and occur in absence of intracranial
infection, metabolic imbalance, or history of afebrile seizures.
Can cause all body convulsions and lasts from few seconds to minutes. Q. Recommend cool bath and acetaminophen.
Two types of febrile seizure simple and complex. The simple febrile seizure is more common and characterized by generalized
tonic-clonic convulsions lasting <15 min. They resolve spontaneously and do not occur within 24 hours or within the same febrile
illness.
Children <6 months of age with a fever should be assessed by an appropriate health-care practitioner.
Fever persisting >3 days in those >6 months of age, recurrent fever or high fever (>40.5°C) should be evaluated by an
appropriate health-care practitioner
QAlerts!
How to manage If a 6-month child is experiencing seizures due to high fever? Recommend cool bath and acetaminophen.
A mother of a 7-month-old child consults because her child has fever 38 degree. She has no other medical conditions and
otherwise healthy and not taking any medications. What would you advice ? a wait and watch b start the treatment c refer to
dr
10. It prevents escape of neurotransmitter from CNS into 11. Lipid soluble drugs cross faster than H 2 O
blood circulations soluble drugs
What is the barrier between cerebral capillary blood and cerebrospinal fluid. The CSF fills the ventricles & the
subarachnoid space (blood brain barrier).
A CNS disease where the myelin sheath of motor neurons is degenerating or being destroyed, which interferes with
neuronal impulses (Multiple sclerosis).
The nerve that pass-through buttocks, posterior thighs down to foot (Sciatic nerve).
What part of brain controls voluntary and involuntary movements (9).
Inappropriate posture of neck, face and limbs is referred as (Dystonia).
Functions of blood brain barrier (5, 10, 11).
The dark granular inside neuronal cell bodies (Nissl substance).
Sciatica is → pain passing through buttocks and thighs .
The longest and largest nerve is --> Sciatic nerve .
What section of brain control involuntary and voluntary movement (9)
What section of brain control balance and coordination (Cerebellum).
Angina pain from shoulder to arm is called -->Referred pain.
Radial nerve damage? Inability to move wrist and finger.
Axillary nerve damage? Loss of sensation in should deltoid muscles (shoulder).
Chronic spasticity is brain disorder is associated with?(Stroke, MS, Cerebral palsy, spinal cord injuries).
What neurological disorder is autoimmune? Multiple Sclerosis.
What are the symptoms of Meniere’s disease? Vertigo, tinnitus.
Bell's palsy is caused by? Viral (HSV-1).
Dysphasia means dysfunction of? Speech.
Nystagmus? Rapid eye movement.
Medulla oblongata relates to?
Corpus collasum relates to?
Febrile seizure caused by?Rise in body temperature usually occurs within 1 to 24 hours fever onset
EVALUATING EXAM CHAPTER 4
Cardiovascular System
Arteries and veins histology
Arteries and veins have walls which consist of three layers: The tunica intima, tunica media, and tunica adventitia.
Arteries will typically have a thicker tunica media and smaller lumen; whereas veins will have a larger lumen and the
thickest layer is the tunica adventitia.
Structural difference between fetal heart and adult heart;
The structure of fetus heart differs than normal postnatal heart. There is an opening in the atrial septum aka foramen
ovale (FO).
QAlerts!
what is the histological difference between artery and vein? Arteries will typically have a thicker tunica media and
smaller lumen; whereas veins will have a larger lumen and the thickest layer is the tunica adventitia.
Conduction (automaticity)
There are four pace makers; Natural (main) pacemaker of heart is SA node. Latent pacemaker of heart is AV node,
bundles of His and purkinje fibres.
Heart rhythm is regulated by the SA node under normal conditions. Heart rate is regulated by sympathetic and
parasympathetic input to SA node.
Q. Phase 1 to starting phase 3 is absolute refractor period or effective refractory period. The cell cannot respond to
any stimuli (NO action potential can be initiated).
During Phase 3 is relative refractory period. The cell ability to respond stimuli increases or cell can respond to strong
stimuli.
Difference actions potentials
● Cardiac action potential ranges from 200 to 400 ms
● Nerve action potential 1 ms
● Skeletal muscle cells action potential 2-5 ms
Electrocardiograph Wave Forms
The electrical activity occurred during depolarization and repolarization transmitted through electrodes attached to
the body and transformed by an electrocardiograph (ECG) in to series of waveforms.
● Q. P wave indicates atrial depolarization.
● PR interval indicates the spread of the impulse from the atria through purkinje fibres (beginning of initial
depolarisation of ventricle).
● Q. QRS complex indicates ventricular depolarization.
● ST segment indicates phase 2 of the action potential the absolute refractory period.
● T wave shows phase 3 of the action potential ventricular repolarization.
● Q. Q-T interval. Mechanical contraction of the ventricles (Torsade’s de pointes).
● U wave caused by hypokalemia.
QAlerts!
Patient with atrial fibrillation. Which wave is affected in ECG? P-wave
Ventricular depolarization appears in? QRS wave
Depolarization is? Inward current or Na+ influx (negative to positive voltage)
In ECG P wave relates to? Atrial depolarization
QT Interval prolongation
The normal QT interval is below 400 to 440 milliseconds (ms) or 0.4 to 0.44 seconds.
Q. QT prolongation is measure of delayed ventricular repolarization and it is polymorphic ventricular
tachycardia. Excessive QT prolongation can predispose myocardium to the development of early after depolarizations
which in turn can trigger re-entrant tachycardia such as Torsades de pointes.
Drug-Induced QT Interval prolongation
Medications that cause QT prolongation: Q. Macrolide (clarithromycin, erythromycin), Q. Fluoroquinolone, (Gatifloxacin,
Gemifloxacin, moxifloxacin, levofloxacin). Q. Ziprasidone, citalopram, escitalopram, quinidine, procainamide, amiodarone,
methadone, ondansetron, domperidone and amitriptyline.
Class 1 drugs (Na+ channel blocker): Quinidine, procainamide, Lidocaine
Class 2 drugs: metoprolol
Class 3 drugs: Amiodarone, dofetilide Sotalol.
QAlerts!
An example of antibiotics that associated with QT prolongation? Macrolides, flouroquinolones
QT prolongation relates to ? measures ventricular repolarization.
Cardiovascular disease
Atherosclerotic cardiovascular disease (ASCVD), are diseases that have atherosclerotic origin which include acute
coronary syndrome, a history of MI, stable or unstable angina, stroke, transient ischemic attack or peripheral
arterial diseases.
Thrombus is blood clot.
● Embolus is moving blood clot.
● Q. Aneurysm is abnormal dilatation of arteries. Can cause stroke.
● Stenosis is constriction or narrowing of opening.
Atherosclerosis
Q. The most common cause of atherosclerosis is due to increased in LDL, which progressively hardens the arteries
and veins. Atherosclerosis is characterized by a build-up in the artery walls. Site of injuries in arteries results
formation of plaques which causes decreased blood flow. Plaques are progressive accumulation of lipids and
inflammatory cells. Sheer stress may result in plaque rupture, collagen exposure, platelet aggregation, and clot
formation.
Most commonly affected arteries are coronary arteries, carotid arteries and peripheral arteries which can cause 3
major types of complications;
Coronary arteries Carotid arteries Peripheral arteries/veins
(cerebrovascular)
Site Heart Brain Thighs, lungs
Diseases Angina, Transient ischemic attack Intermittent claudication
Myocardial infarction (MI) (TIA) Venous thromboembolism
or Acute Coronary artery Acute Stroke Pulmonary embolism
syndrome (STEMI,
NSTEMI).
Symptoms Chest pain, radiating pain FAST
to neck, jaw, arm, back F = Face changes (ask patient
and shoulder (JABS) to smile, one side drops)
A = Arms drifting (raising hand
can drift)
S = Speech change (cannot
repeat the same sentence)
T = Time (every second 1 brain
cell die)
Protocol High fowlers
Morphine iv
Oxygen
Nitroglycerin SL
Aspirin 81 x 4
Beta blockers
Cardiogenic shock
The causes of cardiac shock include acute MI, CHF, valvular dysfunction, arrhythmias (ventricular fibrillation).
Q. Laplace's Law
Laplace's law describes how tension in the vessel wall increases with trans mural pressure. According to Laplace’s
law, tension is proportional to the radius of a sphere.
Inotropic
Inotropic is force of contraction. The ability of the cardiac muscle to develop force at given muscle length.
Positive (+ve) inotropic: Digoxin, ACEI, and dihydropyridine (DHP)-CCB.
Negative (-ve) inotropic: BBs, verapamil, diltiazem.
Chronotropic
Chronotropy is heart rate. The number of action potential that occurs per unit time.
Positive (+ve) chronotropic; DHP-CCB
Negative (-ve) chronotropic; Amiodarone, BBs, NDHP-CCBs, digoxin, "(ABCD)".
Dromotropic
Autonomic effects on heart rate and conduction velocity.
Positive (+ve) dromotropic: Q. Amitriptyline (AV conduction)
Negative (-ve) dromotropic: Na + & K + channel blockers.
Stroke volume
The volume of blood ejected from the ventricle on each heartbeat (pulse rate).
Ejection fraction
The fraction of end-diastolic volume ejected in each stroke volume.
Ejection fraction: Stroke volume/end diastolic volume.
Normal ejection fraction = 55-70%
Low function = 40-55%
If ejection fraction is <40% likely diagnosis of heart failure with reduced ejection fraction (HFrEF).
If ejection fraction is >40% likely diagnosis of heart failure with preserved (HFpEF) ejection fraction.
Cardiac output
Cardiac output (CO) = Stroke volume x heart rate
Pre-load = Volume of blood fills in ventricles in diastolic state
After load= Force to overcome peripheral resistance.
Example: Vasodilators (hydralazine, nitrates, CCBs), ACEi, ARBs, decrease preload and after load.
Cardiovascular Investigations
Q. Blood pressure: Sphygmomanometer.
Q. Normal 120/80
Q. BP is diagnosed in 2 office visits if BP average >140/90 mm Hg, in presence of DM, renal, atherosclerosis, and
cerebrovascular.
Q. Target blood pressure for diabetic and renal disease is <130/80. If the average SBP/DBP is 140-159/90-99 mmHg,
treatment is recommended in the presence of risk factors smoking, family history, truncal obesity, sedentary
lifestyle, male >55 year-old and female >60-year old.
Biological marker (Q. Troponin and Creatine kinase CK-MB)
Q. Electrocardiogram (ECG or EKG) and measures cardiac rhythms. ECG used for excluding atrial fibrillation.
Q. Echocardiogram: Shows the presence of regional valve motion abnormalities, size of heart chambers.
Echocardiogram allows for identification of valvular abnormalities and other MI problems. Blockade in coronary
arteries and veins can be diagnosed by echocardiogram. The presence of regional wall motion abnormalities with
chest pain is suggestive of underlying ischemia.
QAlerts!
Echocardiogram is used for? Valve motion abnormalities
Lymphatic system
Lymphatic system consists of tonsils and adenoid gland, thymus, lymph nodes, spleen, bone marrow and lymphatic
vessels. Functions of lymphatic system includes transports mainly lipid soluble substance.
A brain attack that occurs when a wandering clot (embolus) or some other particle forms in a blood vessel away from
the brain-usually in the heart. (Cerebral embolism) True/False
Drugs that cause –ve chronotropic effect (digoxin, beta blockers). True/False
Endocrine Gland Types of hormone Target tissue Physiologic actions
Hypothalamus Houses releasing and inhibiting Anterior pituitary Controls release of anterior pituitary hormone.
hormones
Anterior Pituitary Thyroid-stimulating hormone (TSH) Thyroid Q. Production of thyroid hormone (T4 and T3, and calcitonin).
gland
Adrenocorticotropic (ACTH) Adrenal cortex Secretion of cortisol
Growth hormone (GH) Bones; soft tissues Stimulates growth of bones and soft tissues
Follicle-stimulating hormone (FSH) Females; ovary Promotes growth of ovarian follicle;
Stimulates estrogen secretion
Males: Testes Stimulates sperm production
Pineal Q. Melatonin Brain; anterior Sets the body’s “time clock”.
pituitary; reproductive Causes sleep in response to darkness.
organs; possibly other Q. Pineal gland shrinks or calcified with aging.
sites. Melatonin is connected with our circadian system rhythm
and environment.
Thyroid Thyroid hormone (Triiodo T3 and Most cells Increases the metabolic rate; necessary for normal growth
levothyroxine T4), and calcitonin (C- and development.
cells).
Q. Calcitonin takes Ca from Blood à Bones.
Parathyroid Parathyroid hormone (PTH) Bone; kidney; intestine Increase amount of calcium in the bloodstream, ¯ amount of
phosphate in the bloodstream.
Q. PTH = Ca (by bone resorption), hypocalcemia stimulate
release of PTH.
Q. PTH = ¯ phosphate
Thymus Thymosin T lymphocytes Enhances the production of T lymphocytes.
Shrink after puberty.
Pancreas Insulin Most cells Promotes use and storage of nutrients particularly glucose,
after eating.
Hyperglycemia stimulate insulin release.
Secreted from beta cells
Glucagon Most cells Maintains glucose levels in the bloodstream during periods
of no food.
Q. Severe hypoglycemia stimulates glucagon release.
Secreted from alpha cells
Q Somatostatin and gastrin Digestive system Inhibits digestion and absorption of nutrients.
Secreted from delta cells Inhibit secretion of insulin, glucagon and gastrin.
F cells? pancreatic polypeptides Somatostatin is antagonist of growth hormone and thus
opposes growth hormone (GHIH).
Z. reticularis Androgens Females: bone and Puberty growth spurt and sex drive in females.
brain
Testes (male) Testosterone Male sex organs; body Stimulates production of sperm; responsible for
as a whole. development of sex characteristics. Promotes sex drive.
Ovaries (female) Estrogen Female sex organs; Stimulate uterine and breast growth; responsible for sex
body as a whole characteristics.
Progesterone Uterus Q. Prepares for pregnancy
**
Negative feedback: The negative feedback occurs when a hormone feedback to
decrease production of its own hormone.
Positive feedback: The positive feedback occurs when a hormone feedback to
increase its own production.
Thyroid Gland
Secretes thyroid hormones LEVOTHYROXINE (T4), TRIIDOTHYRONIN (T3) AND
CALCITONIN, which in turn controls the body’s metabolic rate.
Thyroxin or Levothyroxine Naturally occurs in levo (L) isomer form produced in the
thyroid gland.
Synthesis of thyroid hormones is stimulated by TSH.
Triiodothyronine (T 3 ): Q.Metabolically active form or active thyroid hormone. The
iodide pump (trap) is present in thyroid follicular epithelial cells. Actively transports
iodine into the thyroid follicular cells for incorporation into thyroid hormones.
Levothyroxine T 4 Converts in the liver and other organs to Tiiodothyronin T 3 by Q.deiodination (deiodinase). Controls the rate of
metabolic function in the body.
QAlerts!
· Reaction that converts T 4 to T 3 is? deiodination
· Enzyme that catalyzes conversion of T 4 to T 3 is? deiodinase
Calcitonin (a peptide): Hypocalcemia hormone.
· Secreted by parafollicular cells (C-cells).
· Reduces blood calcium ion concentration by moving Ca from blood to bones.
· Used in treatment of osteoporosis associated vertebral fracture.
· Q. Hypercalcemia stimulates calcitonin production.
Hypothyroidism Hyperthyroidism
Thyroid gland is under active and produces insufficient Overactive thyroid gland causing an abundance of thyroid
thyroid hormone. hormone. Thyrotoxicosis is the general term for over activity of
the thyroid gland.
Q. Fatigue Heat intolerance
Symptoms Sensitivity to cold Profuse sweating (excessively sweating)
Dry flaky skin and coarse hair Diffusely enlarged nontender goiter.
Slowed speech (deep voice) Nervousness, irritability, anxiety and insomnia
Puffy face, hands, feet Weight loss in spite of increased appetite
Hearing loss Tremor and muscle weakness
Decreased libido Tachycardia (Palpitation)
Weight gain Diarrhea
Constipation Oily skin
Impaired memory
Hypertension, bradycardia
Slow return of deep tendon reflexes
Diseases Q. Hashimoto (autoimmune, the most common type of Q. Graves’ disease (diffuse toxic goiter) the most common form
hypothyroidism. Common on in elderly). of hyperthyroidism, autoimmune disorder. Antibodies (long-
Q. Surgical removal of thyroid. acting thyroid stimulators) bind to and activate TSH receptors.
Iodine deficiency.
Myxedema is severe hypothyroid condition. Plummer’s disease (toxic nodular goiter).
Dwarfism
Mental retardation
Q. Serum The most sensitive test for detecting the hypothyroid ¯ serum TSH
TSH assay state.
serum TSH
Free thyroxin This is not separate test but estimation of free T4 level
index (FTI) mathematical interpretation of relationship of RT3U and
serum T4 levels.
(Free T4) Serum free thyroxine ¯ FT4 á T4 indicates hyperthyroidism
(TT3) Serum total triiodothyronine ¯ TT3 Disproportionate rise indicated hyperthyroidism.
Useful in early detection and rule out of hyperthyroidism
Pregnancy Levothyroxine is used to treat. Methimazole or propylthiouracil the treatment of choice.
Adequate dose thyroxin, necessary for development of
the fetal brain.
Serum TSH Q.>5.5 mU/L Q. <0.3 mU/L
Parathyroid Glands
Four tiny glands in the posterior surface of the thyroid gland, which is positioned on the esophagus, produce parathyroid
hormone (PTH), which regulates the calcium metabolism in the body.
QAlerts!
If in elderly increase parathyroid hormone (PTH) increase can cause ? decrease in blood phosphate levels.
Pancreas
Q. Pancreas is present in upper right side of the body and spread to left side. In the pancreas, the islets of Langerhans the acini
which produces digestive enzymes. Islets produce 3 types of hormones;
Insulin produced by beta cells of islets of langerhans.
Glucagon produced by alpha cells.
Somatostatin and gastrin produced delta cells (extra pancreatic cells).
Insulin is peptide with 51 amino acid chain. Stored in vesicles in combination with zinc. Half-life insulin is 3 to 5 min controls
blood glucose concentration.
Q. Insulin (tyrosine kinase receptors): insulin secretion when blood glucose, amino acids and fatty acids).
· Increase glucose uptake into cell.
· Glycogenesis: Increased glycogen storage in liver, and muscle. ↑ glucose uptake
· Decrease gluconeogenesis: Decrease synthesis of glucose from non-carbohydrate ↑ glycogenesis
source. ↓ gluconeogenesis.
· Lipogenesis: Fat/triglyceride storage (adipose tissue). ↓ GLYCOGENOLYSIS
· INSULIN PROMOTES K + UPTAKE INTO THE CELL.
Glucagon
Stimulated breakdown of glycogen to glucose (glycogenolysis) in the liver thus increase blood glucose levels.
Hyperglycemia
HYPOGLYCEMIA HYPERGLYCEMIA
AUTONOMIC Q. Sweating, palpitation, fatigue, hungry, tremors (shaking). Polyphagia, polyuria, hyperglycemia,
FPG <4 mmol/L glycosuria, polydipsia.
<70 mg/dL
CNS Confusion, nervousness, disorientation, dizzy, anxious,
FPG <2-3 mmol/L headache, irritable, blurred vision.
<50 mg/dL
Treatment GLUCOSE TAB, DEXTROSE TAB
STIMULATES SECRETION OF GLUCAGON STIMULATES SECRETION OF INSULIN
FPG: Fasting blood glucose level (8 hours without calories intake); Normal glucose FPG: 5 to 6 mmol/L or 90 to 120 mg/dL.
Diabetes Insipidus (DI)
Q.Anti diuretic hormone (vasopressin) deficiency causes diabetes insipidus Insufficient ADH due to dysfunction of hypothalamic
nuclei (e.g. tumors, hydrocephalus, histiocytosis, trauma). Passage of large volumes of dilute urine. Decrease in ADH causes large
volume of dilute urine, polyuria, polydipsia and polyphagia.
Diabetes insipidus central Diabetes insipidus nephrogenic
There is NO ADH production ADH present but kidney does not respond.
Autoimmune Acquired or drugs (lithium)
Treatment: Anti diuretic hormone
QAlerts!
Diabetic insipidus is caused by deficiency of? ADH or vasopressin
Diabetes insipidus nephrogenic is caused by? Lithium
Thymus Gland
Pineal Gland
· Small cone shaped gland and the smallest of all glands located in mid brain
· Q.Large in children and begins to shrink at puberty.
· Only brain structure that does not come in a pair
· Q.Produces melatonin and dimethyl tryptamine in the dark.
Pineal gland functions includes Influences circadian rhythms e.g. sleep and temperature (Regulates day and night cycle).
Sexual development and regulates the mating behavior
QAlerts!
What hormone glad shrink after puberty? Pineal glad
Adrenal Gland
Ovulation cycle and menstruation
During the menstrual cycle estrogen is produced by the ovarian follicles. After ovulation estrogen is produced by the corpus
luteum. During pregnancy ovulation does not occur. It is suppressed by high levels of estrogen and progesterone's.
Menstrual cycle
Follicular phase Q. Ovulation phase Luteal phase
Day 1 to 13 or variable Day 14 Day 15 to 28
Estrogen elevated LH and FSH Progesterone
Ovulation day = cycle length- 14 days. Uterine contraction
Q.Pregnancy test
Human chorionic gonadotropin (hCG) hormone levels are elevated in first 3 months of pregnancy (first trimester).
Progestin's in pregnancy is produced by ovaries, corpus luteum and placenta.
QAlerts!
· Ovulation Tests detects? LH
· Pregnancy test detects? hCG
· How many days after ovulation cause menstrual periods? 14 d
· What hormone does the pregnancy blood test detect? progesterone
Menopause
Cessation of menstrual periods for at least 6 months to 1 year is referred as menopause. Occurs when the ovaries stop producing
estrogen. Ovarian follicles are depleted at approximately 51 years of age so the average age for menopause is 51 years.
Early menopause is defined as menopause before 45 years of age and premature is before 40 years of age.
Q. There are 2 most common symptoms
Vasomotor symptoms: Hot flashes, night sweat, mood swings, sleeplessness, lethargy, and depression.
Urogenital atrophy symptoms: This leads to dryness of the vagina, dyspareunia (painful intercourse).
HYPER HYPO (menopause)
Estrogen Weight gain Q.Hot flushes, night sweat, dry skin, mood swings, vaginal
18-CARBON Increase risk of blood clot, mood changes, breast atrophy, dryness, bone loss, yeast infection. Urinary
STEROIDS cancer, headache, edema incontinence.
QAlerts!
What is the average age for menopause in Canada? 51 yo
Most common symptoms of menopause? Hot flashes
What is NOT a menopause symptom? Flank pain
25. Polydipsia
Renal System
Nephron
A nephron is the basic unit of renal function. There are millions of nephrons present in each kidney. Nephron has three major
functions.
Chronic Kidney Disease Electrolyte Imbalances
Proteinuria and hematuria possible.
CKD can cause azotemia, anemia, vitamin D 3 deficiency, decrease Ca concentration, and increased blood activity (acidosis).
Q. The production of active form of Vitamin D 3 1, 25-dihydroxycholecalciferol in the kidney is catalyzed by enzyme 1-alpha
hydroxylase.
1-alpha hydroxylase
Vitamin D2 ----------------------------à Vitamin D 3
Q.The 1-alpha hydroxylase activity is increased by ¯ serum Ca, PTH levels, ¯ serum phosphate.
Q.CKD can cause decrease drug (metabolite) clearance and drug half-life (T 1/2 ) increase.
QAlerts!
Patient with CKD, experiencing metabolic acidosis. It is treated by? Sodium bicarbonate
Acute Renal Failure (ARF)
The acute renal failure (ARF) is rapid decline in the renal ability to clear <15 ml/min, the blood of toxic substances, causing
accumulation of metabolic waste products, like blood urea nitrogen.
PRE-RENAL ARF INTRINSIC ARF POST ARF
Q. In adequate blood perfusion, CHF, Aminoglycosides, NSAIDS, nephrotoxic drug Cancers in ureter or bladder.
hemorrhagic, hypovolemia, severe example….
blood loss, dehydration, sepsis. Infections, sepsis, radiocontrast media,
metformin
QAlerts!
Prerenal acute renal failure is caused by? Low blood perfusion
Hypercalcemia
Hypocalcemia
· Drugs that prevent bone resorption (death) are referred as antiresorptive agents.
· Antiresorptive agents are bisphosphonates, clodronate disodium, pamidronate disodium and
zoledronic acid.
Potassium (K + )
Potassium distributed primarily in intracellular (98%) and extracellular (2%) in muscle tissues. Plays role in acid base
equilibrium acidosis means serum concentration is influenced by changes in pH. Increase in arterial pH serum potassium will
decrease. Potassium excretes from kidneys.
· Major cation in intracellular space. Most abundantly found in fruits (bananas, tomatoes) and vegetables cucumber, leafy
green vegetable.
· Maintenance of proper electrical conduction in cardiac and skeletal muscles (muscle and nerve excitability).
· Q. Range of normal value 3.5 to 5 mEq/L.
Potassium regulated by
· Kidneys (renal function)
· Aldosterone
· Arterial pH
· Q. Insulin (insulin decrease K + in blood by shifting K + into cell).
· K + supplement intake
· Sodium delivery to distal tubule.
Hyperkalemia
Serum potassium greater than 5 mEq/L is defined as hyperkalemia.
Q. Mild hyperkalemia is plasma K + 5–6 mmol/L and Severe hyperkalemia K + >6.5 mmol/L
Causes: Q. Renal failure, and drugs. The drugs that cause hyperkalemia include K + sparing diuretics (Spironolactone,
Triamterene, and Amiloride), ACEi, and ARBs etc.
· Adrenal insufficiency (aldosterone hormones).
· During vigorous exercise.
· Cellular breakdown (tissue damage, hemolysis, burns, infections).
· Q. Metabolic acidosis and cardiac arrest.
Q. Aldosterone increase K + secretion: Drugs that inhibit or blocks aldosterone hormone can cause hyperkalemia such
potassium sparing diuretics, sulfamethoxazole, ACEi, and ARBs.
Hypokalemia
Serum potassium levels less than 3.5 mEq/L is defined as hypokalemia.
less than 3.5 mmol/L, can be mild (3–3.5 mmol/L), moderate (2.5–3 mmol/L) or severe (<2.5 mmol/L).
Symptoms: Malaise (feeling NOT well), confusion, dizziness, ECG changes, muscle weakness and pain.
Causes: Excessive mineral corticoid activity, vomiting, and diarrhea. Diabetic ketoacidosis.
Drugs that cause hypokalemia. Q. Diuretic Thiazide, loop diuretics and acetazolamide increase secretion of K + , Corticosteroids,
penicillin (piperacillin, ticarcillin), beta 2 agonist, and amphotericin.
· Glycosuria
· Alkalemia
· Administration of insulin and glucose.
QAlerts!
Normal level of serum potassium? 3.5 to 5 mEq/L
Medications that increase serum potassium levels? ACEi, ARBs, K+ sparing diuretics.
Medications that decrease serum potassium levels? Thiazides, loop diuretics, corticosteroids
Magnesium
Magnesium homeostasis; 99% of intracellular (17% of total body content in the muscle) or in the skeleton. Normal serum
concentration 1.8 to 2.4 mg/dL (about 30% bound to proteins).
Hypomagnesia
Serum levels of magnesium lower than 1.8 mg/dL (1.5 mEq/L).
Signs and symptoms: muscle weakness, cramps. Magnesium depletion can influence potassium and calcium
homeostasis so can cause hypokalemia and hypocalcemia.
Q. Drug that causes hypokalemia can cause hypo magnesia as well.
Chloride (Cl -)
· The most abundant extracellular anion is Cl - is the most abundant extracellular cation). + (Na
· Maintenance of acid base balance relationship between Na, and Cl.
Hyperchloremia
Caused by:
· Renal insuffi ciency when chloride intake exceeds excretion
· Dehydration
· Excessive salt intake
Hypochloremia
Caused by:
· Excess loss of GI fluids
· Diuretic therapy: Thiazide, and loop diuretics. Hypochloremic alkalosis is caused by: thiazides.
· Fasting
· Adrenal insuffi ciency
Sodium (Na +)
· Sodium is the predominant cation of the extra cellular fluid (ECF).
· Q. Norma sodium levels (135 to 147 mEq/L or mmol/L).
· Sodium is essential in establishing osmotic pressure relation between intracellular and extra cellular
fluid.
Hyponatremia
· Caused by cirrhosis, CHF, nephrosis or the administration of osmotic active solutes such as albumin or
mannitol (osmotic diuretic).
Hypernatremia
Caused by:
· Loss of free water (not body fluid)
· Loss of hypotonic fluid
· Excessive sodium intake
· Drugs that contain (beta lactam, ticarcillin, antacids such as sodium carbonate).
Q. HYPO HYPER
CALCIUM LOW PTH, FUROSEMIDE, HIGH PTH, THIAZIDES,
CORTICOSTEROIDS,
POTASSIUM THIAZIDES, LOOP K + SPARING DIURETICS, ACEI, ARB,
CKD
PHOSPHATE HIGH PTH CKD
SODIUM Chronic Kidney Disease (CKD)
QAlerts!
Normal sodium serum levels? 135 to 147 mEq/L or mmol/L
Acid Base Disorders
Body produces two types of acids; Volatile (CO 2 ) and non-volatile or fixed acids (HCl. phosphoric acid,
sulfuric acid). Q Normal blood pH 7.35 – 7.45. CO 2 is produced from aerobic metabolism of cell.
Metabolic acidosis
Q. Liver is located at right side of the abdominal cavity. Liver main functions include metabolism, storage and detoxification.
Metabolism: Excessive blood glucose stored in liver as glycogen, converts glycogen to glucose. Protein breakdown to ammonia
and liver takes up and convert to urea.
Most drugs are metabolized in liver and there are transporters for anions, bile salts, cations, and neutral organic
compounds release in small intestine.
Blood circulation to liver
Q. Hepatic artery directly bring blood from heart
and hepatic vein bring nutrient rich blood from
gastrointestinal system. Hepatic portal vein and artery
merge at portal triad liver functional unit hepatic lobules.
Hepatocytes metabolize heme and break down to iron and
bilirubin which release in to bile.
Which leaves body from stool.
Q. Oral drugs passage to liver
GI tract à Mesenteric veins à portal veins à liver à hepatic vein à heart à systemic circulationà Renal or hepatic elimination.
Enterohepatic recirculation
· This term refers to Q. drugs emptied via bile into the small intestine and then reabsorbed from the intestinal lumen into PORTAL
VEIN to the systemic circulation.
· It can allow the body to conserve endogenous substances such as bile acids, vitamins D and B 12 , estrogen etc. It may
be responsible for some of the long half-lives of drugs.
· Antibiotic therapy interferes with the process of enterohepatic recirculation by drugs, which have been conjugated can be
hydrolyzed by gut enzymes such as glucuronidase and then reabsorbed as the active drug or as a metabolite. A decrease in
bacterial flora as a consequence of antibiotic therapy can decrease the amount of sulfatase and glucuronidase containing
bacteria. This could then lead to an increased rate of elimination of the drug.
QAlerts!
1) Enterohepatic recirculation is? recirculation bile from small intestine to liver.
2) Drugs that involve in enterohepatic recirculation? Increase action of oral drugs with phase II metabolism.
3) Cholestyramine binds with bile and prevents reabsorption of bile into liver in duodenum.
4) Decrease in blood flow to liver alters extent of drug metabolism.
Liver biochemistry
Conjugated Bilirubin
ALP Transaminases
Elevation suggests liver disease.
ALT (liver specific) AST
Hepatitis A ↑ ↑ ↑
Hepatitis B&C ↑ ↑ ↑
Liver cirrhosis ↑ ↑ or can be normal ↑ or can ↑
be normal
Q. Jaundice (cholestasis) ↑ ↑ ↑ (characteristic)
↑
(specific)
Alcoholic liver ↑ ↑↑
disease
AST and ALT = Transaminases. Produce after liver inflammation. Elevation of AST or ALT useful for measuring liver cell injury.
Elevation indicates acute injury to liver.
ALP (alkaline phosphatase); have 5 minor sources (liver, bile duct, kidney, bone, placenta). AST can also come from muscle
( Q Jaundice + ↑ALT).
Q. Alcoholic liver disease AST to ALT ratio is >2:1.
Q. ALT>AST by 1000 x in acute viral hepatitis.
Q. Alpha 1- antitrypsin (A1AT) deposition of excessive abnormal A1AT occurs in cirrhosis.
Q. Liver biopsy: is valuable for diagnosis and grading chronic liver diseases.
CHRONIC LIVER DISEASES
SPONTANEOUS BACTERIAL PERI CHRONIC HEPATIC ENCEPHALOP
TONITIS CHOLESTASIS (OR Q. Q. ASCITES ATHY
OBSTRUCTIVE JAUNDI
CE)
History of fever, abdominal pain. Q. Due to Aldosterone Confusion, psychosis.
obstruction outside retains water.
liver or Excessive
physical blockage (bile fluid retention
duct or gallstone). in peritoneal cavities.
Yellow skin, eye, itchy skin.
Abdominal pain, dark urine.
Ascites can predispose Q. Hyperbilirubinemia (á urine, Abdominal Ammonia
to bacterial peritonitis plasma) áplasma conjugated bili cancers, abdominal infec released in blood.
rubin. tions, TB and
GI problems.
âurobilinogen in the urine.
Yellow itchy skin.
Treatment: antibiotics Treatment. Antihistamine Q. Drug of choice Q. Lactulose can
or cholestyramine is spironolactone. Add; trap ammonia gas.
Furosemide,
metolazone
Peritoneal
dialysis associated infection: Associat
ed risk with S. aureus in peritoneal
catheter in dialysis.
Ascites or Hydroperitoneum
· The accumulation of fluid in peritoneal cavity causes abdominal distention is referred to as ascites; this is due to high
plasma aldosterone levels. Symptoms include abdominal distention. Q. Ascites is caused due to infections such as
tuberculosis, heart failure, cirrhosis, and portal hypertension, and various cancers.
· Q. Drug of choice is spironolactone is inhibitor of aldosterone because aldosterone
hormone increases Na/H 2 O retention. Alternate furosemide can be added to enhance diuresis.
Hepatic Encephalopathy (Porto Systemic Encephalopathy)
Condition in which brain function is impaired by presence of toxic substances, absorbed from colon, which is normally detoxify
and removed by liver. This condition occurs in severe liver damage such as liver cirrhosis.
· Symptoms include: Drowsiness, confusion, difficulty in performing task (e.g. writing) and coma.
· Q. Drug of choice is lactulose to achieve 2 to 3 bowel movement a day. If no improvement in 1 to
2 days add metronidazole.
Wilsons Disease
· Q. Excessive copper can cause Wilsons disease. The drug of choice is the penicillamine and treatment is lifelong.
Pyridoxine (vitamin B 6 ) 25 mg daily should be given with penicillamine to counteract its anti-pyridoxine effect.
· Avoid food that has high copper content such as peanuts, chocolate, shellfish, mushrooms, and liver.
Cholestatitis or cholestasis
Retention of bile acids because of the obstruction of bile ducts. Cholestatitis can lead to hyperbilirubinemia.
Chronic Cholestasis (cholestasis jaundice, obstructive jaundice, or jaundice):
· Cholestasis is a condition associated with gallstone, in which obstruction of bile from liver to intestine, it is also referred
to as obstructive jaundice. Symptoms are pruritus (itching) and are due to hyperbilirubinemia associated with liver
Liver disease in which liver cells becomes scarred, severely damaged and replaced with
fibrous tissue. Liver cirrhosis can cause by hepatitis B or C, excessive ethanol consumption, fat collection in liver due
to obesity, high cholesterol and diabetes, bile duct problems, autoimmune diseases
and Q.drugs associated with liver cirrhosis are amiodarone, methotrexate and methyldopa.
Chronic liver disease à compensated cirrhosis------------- à Decompensated cirrhosis à Death
Development of complications Variceal haemorrhage Ascites Encephalopathy Jaundice
Child Pugh Scoring is used to classify level of liver cirrhosis to guide drug dosing or appropriateness of using
specific therapies in patient with cirrhosis.
Viral Hepatitis
There are 5 types of hepatitis viral infection, hepatitis A, B, C, D, and E. However, the common infections are
hepatitis A, B and C.
Most common symptoms of hepatitis are flu like symptoms, loss of appetite, fatigue, mild fever, muscle or joint aches,
nausea and vomiting. Less common symptoms are light colored stools,
jaundice (yellowing of skin and whites of the eye), generalized itching, internal bleeding and altered mental state.
Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Types RNA DNA RNA RNA RNA
Route transmits Parenteral, Parenteral, blood, sexual Parenteral, blood, sexual
Oro-fecal (water,
blood, sexual, needle.
food, toilets).
Severity Q.Acute Q. Chronic Q.Chronic mild Mild
(mild) (severe)
Incubation 30 days 90 days 40 days 50 days
Prevention Vaccine 1 dose Vaccine (3 Q.No vaccine
(travelers), >1 yo. doses 0,1&6 months)
Treatment Hep Nucleotide analogs: Tenofovir, Adefovir Q Direct
A immunoglob ulin acting antivirals (DAA)
Nucleoside analogues: Lamivudine, Entecavir NS5B
polymerase inh.
Peginterferon- alpha 2a. NS5A inh and NS3
or protease inhibitors.
Hepatitis A
· Hepatitis A is acute infection.
· Q. Transmits through food contaminations such as water, food or orofecal.
· Vaccine available.
· Hepatitis A vaccine is recommended to travelers., given to children >1 yo.
Hepatitis B and C
· Q. Hepatitis B and C are chronic. Hepatitis B is 90% chronic in children and 5% in adults. The most
common is hepatitis B.
· Hepatitis B is DNA type of virus where as other hepatitis is RNA type.
· Q. Transmission through body fluids, such as blood transfusion, sexual contact and sharing needles (drug ab
use and spa), mother to new born transfer and occupational exposure.
· Hepatitis C is often chronic in adults (acute hepatitis C is 80% becomes chronic likely within first yea
r of infection).
· Hepatitis C has NO vaccine.
· Hepatitis B vaccine also protects hepatitis D infections.
Hepatitis a Hepatitis b Hepatitis C
No treatment needed (infected get Peginterferon shots (4 mo) Q. Direct Acting Antivirals (DAA): Sovaldi (sofosbuvir)
well in their own) Lamivudine po (1yr) Adefovir po 2 Harvoni (ledipasvir + sofosbuvir).
year Tenofovir Q. Peginterferon combination with antiviral ribavirin,
Lamivudine is Nucleoside analogues (Nucleoside has two units’ base and ribose)
efovir and Tenofavir Nucleotide analogues. (Nucleotide has three units’ base, ribose, phosphate). PEGinterferon reduces the clear
ance and allows for once weekly administration.
Q. All types of hepatitis contagious usually spread by person-to-person also may spread by sexual contact.
QAlerts!
What is correct about hepatitis A? Acute, transmitted by food and water, vaccine only over 1 year age.
What is the drug of choice for Hepatitis C? DAA Hepatitis B vaccine dosing schedule? 0, 1, and 6 months
All of the following viral infections are transmitted by sexual contacts, except? Hepatitis A
What opportunistic infection in HIV patient that require liver transplantation a hepatitis a , b/ hepatitis b , c. hepatitis c
Which patient is best candidate for liver surgery or live transplant? than what should be measure
we should look up on? A.AST B. ALT C. ALP
Drug dosing in liver diseases
In liver diseases changes in phase 1 drug metabolizing reaction such as oxidation via CYP450, reduction and hydrolysis.
Phase II conjugation reaction such as glucuronidation, sulfation, methylation and acetylation. Drug induced liver cell injury
can occur within 1 year of initiating offending agent.
DRUGS THAT CAN CAUSE HEPATOTOXICITY
Drugs Avoid /TIPS
Acetaminophen > 4 g daily but chronic liver diseases >2 g/day
Tetracycline >2 g daily
Methotrexate >25 mg/wk
Leflunomide
Vitamin A chronic use over 40,000 U daily
Salicylates (ASA) chronic use >2 g daily
Iron single dose >1 g
Cyclophosphamide
6-Mercaptopurines
Estrogen
Erythromycin estolate.
Phenytoin Can cause toxicity like cerebral dysfunction (Nystagmus)
Acarbose
Allopurinol
Fluoxetine
losartan
Carbamazepine, valproic acid
Propylthiouracil
Amiodarone Liver cirrhosis
QAlerts!
A patient with hepatitis C experiencing severe headache. Which analgesic should avoid using? acetaminophen
. Penicillamine 2. Ascites 3. Wilsons disease
Liver is located in? Right side of abdomen and protected by rib cage.
Ascites is caused by? (Infections, TB, cancers and chronic liver diseases GI surgery )
What is a DNA type of virus (6)
Accumulation of fluid in peritoneal cavity (2)
What is the drug of choice to treat Wilsons disease (1)
Retention of bile acids because of obstruction of bile ducts (4)
What type of hepatitis infection that has no vaccine for prevention (7)
What is the drug of choice to treat ascites (18)
Lactulose is used to remove excessive ammonia that produced in liver andreleased into blood circulation. What type of
chronic liver disorder? (Hepatic encephalopathy)
What type of hepatitis is chronic → B and C
What is the treatment of chronic hepatitis C → Direct acting antivirals,Peginterferon’s alpha.
Hepatitis A transmits by → water and orofecal.
Hepatitis B and C transmits by → Sexual contact
If patient takes Hepatitis B vaccine, this also protects →Hepatitis D
What is first line therapy for hepatitis C? → Direct acting antiviral.
Cholestasis: Retention of bile acids because of the obstruction of bile ducts. Example: Penicillins (isoxazole type)
(True/False)
Drug induced cholestasis can lead to hyperbilirubinemia example: Rifampin (True/False)
Bacterial peritonitis: Chronic liver disease, history of fever, abdominal pain. (True/False)
Causes of ascites include → infections, TB, cancer, GI surgeries, chronic liver disease (True/False)
Lactulose is used in what type of chronic liver disorder → hepatic encephalopathy (decrease NH 3 ) (True/False)
Respiratory System
Pleural cavity is the space between two pleurae (visceral parietal) of the lungs. It is filled with
fluid. It is bounded with double layer called pleura. This lubricated cavity allows the lungs to move freely
during breathing.
Anatomy of upper respiratory tract consist of;
· Nose, sinuses, and nasal passages
· Pharynx
· Tonsils and adenoids
· Larynx and trachea
Upper respiratory tract infections
URT etiology Affects
Common cold rhinovirus Nasopharyngeal tract
Acute rhinitis Inflammation of nasal mucus membrane
Sinusitis Inflammation of mucous membrane of sinuses
Acute pharyngitis Inflammation of throat
Anatomy of lower respiratory tract consist of; Trachea and bronchi.
LUNG VOLUME
Tidal volume: The volume inspired or expired with each normal breath. Can be measured
by Q. Spirometer (FEV 1 ). In asthma, expiratory flow rate decreased.
Q. The residual volume cannot be measured by spirometer.
Inspiratory reserve volume (IRV): The volume that can be inspired over and above the tidal volume. It is used
during exercise.
Expiratory reserve volume (ERV): The volume that can be expired after the expiration of tidal volume.
Residual volume (RV): The volume that remains in the lung after a maximal expiration. Keeps lungs from collapsing.
LUNG CAPACITIES
VITAL CAPACITY = Tidal Volume + Inspiratory reserve volume (IRV) + expiratory reserve volume (ERV).
Q. FORCED VITAL CAPACITY (FVC) = Volume of air that can be forcibly expired after a maximal inspiration.
INSPIRATORY CAPACITY = TV + IRV; is the total amount of air that can be inhaled and is calculated by adding the tidal
volume and inspiratory volume.
TOTAL LUNG CAPACITY = TV + IRV+ERV + RV; The total lung volume is 4200 to 6000 ml. The sum of
all four lung volumes (tidal volume, inspiratory lung volume, expiratory lung volume, residual volume). The volume in
the lungs after maximal inspiration.
FLOW RATES: Used to assess asthma and related conditions.
FEV1 FVC
The amount of air that you can quickly
The amount of air that you can quickly and forcibly exhale in 1
and forcibly exhale after maximal inhalation.
second after maximal inhalation.
QAlerts!
The amount of air that you can quickly and forcibly exhale after maximal inhalation is ? Forced vital capacity (FVC)
Spirometer is the gold standard for the diagnosis of Asthma and COPD? What volume is not
measured in spirometer? Residual volume
Cellular respiration
During aerobic cellular respiration glucose reacts with oxygen forming ATP that used by the
cell. Carbon dioxide and water are created as by product.
What triggers respiration? co 2
Spirometer
Measure volume that has been exhaled at the end of the first second (FEV 1 ). Q. The spirometer is
gold standard for both asthma and COPD diagnosis.
Forced expiratory volume (FEV 1 ): The volume of air that can be expired in 1 second after
maximal inspiration. NORMALLY 80% OF FORCED VITAL CAPACITY. This is measured by spirometer.
· FEV 1 predicted value >80% is normal (adult <70% normal, in children >80% normal)
· FEV 1 65-80% Mild
· FEV 1 50-65% Moderate
Q. FEV 1 <50% severe and is indicator of very low respiratory function.
QAlerts!
What device is used to rule patient choric obstructive pulmonary disease? spirometer
Q. Peak flow meter
Is test to determine asthma severity for patient at home and it is recommended for severe asthma patient as
asthma action plan. This test measures the highest forced expiratory flow. It consists of three-color signals.
Q Pulse oximetry +/- arterial blood gasses (ABG)
The arterial blood gas (ABG) test measures the acidity (pH) and the level of oxygen and carbon dioxide in the
blood from an artery.
If FEV 1 <1 L or <40% or SpO 2 <92% or clinical signs of respiratory failure or Congestive heart failure. Pulse oximetry+/-
arterial blood gas (SpO2 ): determines the requirement oxygen therapy.
SpO 2 >95% = normal
SpO 2 91-94% = borderline
SpO 2 85-90% = Immediate intervention because low of blood
oxygen. SpO2 <85% = administer 100% oxygen.
Respiratory rate
The respiratory rate is set and controlled by the respiratory center in medulla oblongata of the brain.
Normal respiratory rate for healthy adult at rest 12-16 breaths/
minute. Neonates 30-40 bpm
Elderly >80 yo: 10-30 bpm
Lung cells
Small cells and Non small cells
Cell types of the alveoli
Type 1: simple squamous cells where gas exchange occurs.
Type 2: septal cells: free surface has microvilli and secrete alveolar fluid containing surfactants. Type 3:
dust cells: wandering microphages remove debris.
Non-small cell lung cancer (NSCLS) and small cell lung cancer (SCLC) and mesothelioma are among most common
lung cancers.
Q. Cystic fibrosis
Autosomal recessive disorder that is caused by a mutation on chromosome 7 and inherited
disease. This mutation results in a defective membrane CT channel (CFTR) cystic fibrosis is multiorgan disease.
Q. Signs: The mutation leads to secretion of thick mucus, very sticky and which lodges in lungs.
Also additional complication in liver and pancreas can occur.
Symptoms: Shortness of breath and cough. Recurrent pulmonary infections with P. aeruginosa.
QAlerts!
9-year old child with history of poor growth and chronic cough. Here sweat test was positive and her
lab investigations she was diagnosed with cystic fibrosis. What therapies used for cystic fibrosis?
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are used for treatment of cystic fibrosis,
and pancreatic hormone replacement therapy
Croup
Croup (laryngotracheobronchitis) is a common cause of upper airway obstruction in children. It is most prevalent in
the late fall to early winter months. Commonly begins with common cold and slowly turns into
characteristic cough that sound like a seal barking.
Common in children <6 years of age.
There are 3 different types of croup: Q. the most common is viral croup caused by parainfluenza virus. Spasmodic croup
is caused by allergy or reflux from stomach. Croup with stridor can become life-threatening.
Q Croup symptoms: cough that turns into seal bark, runny nose, stuffy nose, losing voice, and fever.
A single oral or parenteral dose of dexamethasone 0.6 mg/kg effectively relieves croup symptoms in 2-3
hours. Use before bedtime to prevent suddenly wake up with a barky cough and difficulty in breathing. Avoid
OTC cough syrups.
QAlerts!
2-year-old child present with a barky cough, which is typically worse at night. His barky
cough accompanied by inspiratory stridor, hoarseness and respiratory distress. Barking cough sounds
are symptoms of? Croup
TIPS
1 Asthma 2 Emphysema 3 Dyspnea
4 COPD 5 Emboli formation in lungs 6 Autosomal recessive disorder
7 Wheezing 8 Vital capacity
· Tidal volume is? The volume inspired or expired with each normal breath.
· What is volume is not measured by spirometer? Residual volume
· What diagnostic test is used to rule out asthma? Spirometer
· What respiratory condition occurs in bronchus or bronchial tube (Asthma).
· What respiratory condition can occur in bronchioles & alveoli (COPD).
· Pulmonary embolism is floating clot in blood circulation in the lung tissues.
· Cystic fibrosis is a --> multi organ disease but mainly effect on lungs due to the long thick
lung secretions blocks small airway and thus inflammation (A restrictive respiratory disease).
· Cough in asthma sounds like--> Wheezing
· Alpha1-antitripsine deficiency? COPD
· When maximum amount of air a person can expel from the lung after a maximum inhalation,
is referred as? Forced Vital capacity (FVC). This depends on age, gender, height, mass and ethnicity.
Diffi culty in breathing (dyspnea)
Permanent enlargement of the alveoli (emphysema)
Emphysema is...(COPD)
What respiratory condition occurs in bronchus or bronchial tube (Asthma)
What respiratory condition can occur in bronchioles & alveoli (COPD)
Cough in asthma sounds like--> Wheezing
What is defined as maximum amount of air a person can expel from the lung after a maximum inhalation? Forced vital
capacity (FVC)
Pulmonary embolism is floating clot in blood circulation in the lung tissues.
What is a restrictive respiratory multi organ disease but mainly effect on lungs due to the long thick lung
secretions blocks small airway and thus inflammation (cystic fibrosis)
Alpha1-antitripsine deficiency? Family history of COPD.
Common cause of croup is? Parainfluenza virus
Urinary System
The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the ure- thra.
Urinalysis is a test that studies the content of urine for abnormal substances such as protein or signs of
infection. Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from
the bladder through the urethra.
INFECTION TREATMENT
LOWER UTI Bladder Q. Cystitis, the most common infecting Q. 1st line 2nd line
organism is E. coli (80- 90%). P P P P
Usual presenting symptoms; In- ternal dysuria, SMX/TMP 3d, or Nitrofurantoin 5 Ciprofloxacin bid f3d, norfloxacin,
frequency, su- prapubic discomfort and days Or levofloxacin 3d
urgen- cy. Trimethoprim 3 d Or Or
Fosphomycin single dose. Cephalexin po 7 d
Urethra Urethritis
UPPER UTI Ureter Ureteritis
evening). Pregnancy: avoid fluoroquinolones.
Causative agents of UTIs: E. coli is the most common in community acquired (80%), and hospital (50%).
UNCOMPLICATED UTI COMPLICATED UTI
The most common cause of UTI is E. coli. Internal Occurs in patient with comorbidities such as diabetes, BPH, kidney stones,
dysuria, frequency, suprapubic dis- comfort, menopause, immunodeficiency, pregnancy and men.
urgency. Burning upon Q. High fever, turbid urine or cloudy urine, blood in urine hema- turia, pyuria, vom
urination, nausea & vomiting. NO FEVER/someti
iting and sepsis.
me
can be fever.
Burning upon urination. Nausea & vomiting. Example: pyelonephritis.
QAlerts!
What is not a symptom of uncomplicated urinary tract infection? Fever, blood/pus (turbid)
urine. What antibiotic is not used for complicated urinary tract infection? Nitrofurontoin.
Q. Physiological factors that increase
risk of urinary tract infections.
· Decrease resistance of mucus membran
e. (e.g. meno- pause).
· Increase in vaginal pH.
· Colonize colon spread to UTI.
· Colonization of urethra and peri-urethral tissue.
Asymptomatic bacteriuria
Q. Bacteria present in urine (at a concentration ≥10 8 cfu/L) and without urinary tract infection symp-
toms.
Q. Asymptomatic bacteriuria antibiotic prophylaxis is used for pregnant and before urethral resection
of prostate.
Q. Prophylactic antibiotic in pregnancy: amoxicillin, amoxi/clav, cephalexin, nitrofurantoin, fosphomy- cin.
Ceftriaxone preferred for pyelonephritis.
QAlerts!
Who will get prophylactic antibiotic for asymptomatic bacteria? Pregnant wome
Prostate
There are 3 main conditions that affect bladder, BPH, prostatitis, and prostate cancer.
The prostate is located at the bottom of the bladder and surrounds the urethra. BPH is an enlargement of the
prostate gland that can interfere with urinary function in older men. It causes blockage by
squeezing the urethra, which can make it difficult to urinate.
Q. Prostate-specific antigen (PSA) test is used to screen prostate cancer. The PSA values below 4.0 ng/mL is
normal. Prostate Specific Antigen (PSA) used to diagnose or rule out prostate cancer and also rose in BPH.
Benign prostatic hyperplasia (BPH)
BPH is a condition in men that affects the
prostate gland, which is part of the male
reproductive system. Men with BPH frequently
have other bladder symptoms
including an increase in frequency of bladder e
mptying both during the day and at night.
Q. Symptoms: Urine obstructions symptoms include frequent urine, drop by drop, incomplete voiding, nocturia and also
include irritation symptoms.
Treatment: Q. The drug of choice to decrease prostate size finasteride 5 mg, Dutasteride.
Q. 5-ALPHA REDUCTASE
TESTOSTERONE --------------------à DIHYDROXY TESTOSTERONE ( PROSTATE SIZE)
Androgenic alopecia is treated by finasteride 1 mg.
Alpha blockers alfuzosin (1aRaR selective), tamsulosin, terazosin, sildosin is used to treat symptoms.
Bladder neck/sphincter contraction is due to alpha agonist activity.
Q. Tadalafil 5 mg also used to urinary sign symptoms in BPH.
QAlerts!
What is NOT a symptom of BPH? Jet urination
What alpha adrenergic blockers are used for treating benign prostatic
alpha reductase
Urinary incontinence
Involuntary leakage of urine. There are many causes and types of incontinence. Treatment
range from kegel exercises to surgery. Women are affected by urinary incontinence more often than men.
Detrusor muscle contraction due to parasympathetic activity helps urine voiding or FLOW. Tightening of sphincter is d
ue to anticholinergic activity helps to URINE STORAGE.
Q. Bladder relaxation is due to beta agonist activity. Q.Bladder neck/internal sphincter contraction is due to alpha
agonist activity
QAlerts!
Overactive bladder or urge incontinence first line treatment? Pelvic floor muscle training PFMT (kegel)
Urinary Retention
Q. Post void residual (PVR) volume >300 mL can be indicator or urinary retention. A PVR urine >50 ml is
sig- nificant amount of urine and increases the potential for recurring urinary tract infection.
In adults >60 yo PVR 50-100 ml of residual urine may remain after each urine because of â contractility of
the detrusor muscle.
Drugs that cause urinary retention: Anticholinergic, antihistamine
TCA. QAlerts!
Most common drugs that cause urinary retention side effects? anticholinergic
Nephrolithiasis or Kidney stones
Kidney stones or calculi are hard insoluble crystallized minerals, salts that have formed from filtrate produced
by nephron. Stones can be found in anywhere in urinary system and can be large size to very small size. The
process of stone formation is urolithiasis, renal lithiasis, or nephrolithiasis . There different kidney stones
include, calcium oxalate stones, uric acid stones, struvite stones and cystine stones.
Calcium oxalate stones
Calcium oxalate stones forms in acidic urine due to increase amount of calcium and oxalate in urine. Normally
calcium and oxalate bind together and excrete in stools. However, some risk factor can cause excessive
oxalate or calcium such as hypercalcemia, medication induced hypercalcemia, hyperparathy- roidism, high
intake of food containing sodium decrease calcium reabsorption thus more calcium urine. High intake of
oxalate foods and gastrointestinal conditions ulcerative colitis digest fat and form fat complex with
calcium and leaving oxalate into urine.
Uric acid stones
Excessive uric acid or hyperuricemia, gout, dehydration, metabolic complications of diabetes,
high intake of purine and protein rich foods.
Cystine stones
Cystine stones is rare caused by genetic disorders of excessive cystine amino acid in paroxysmal convoluted tubu
le.
Calcium phosphate stones
Calcium phosphate stone is rare of stones forms in renal tubule in alkaline urine.
Struvite stones
Struvite stone are rare forms cause by urinary tract infections bacteria causes urine to be alkaline, mag- nesium
and ammonium phosphate.
Stones (calculi) can form mainly in kidney however can forms anywhere in urinary tract and pain radiates in
flank area, sharp, sudden severe pain, may be intermittent depends on stone movement, nausea, vomiting,
bleeding (hematuria), obstruction of flow of urine, or an infection. Depending on the site of stone it
is referred as kidney stone, ureteral stone, or bladder stone.
Q. Drugs associated with urolithiasis/ nephrolithiasis Causes/recommendation
Fibrates (Fenofibrate, Gemfibrozil) Avoid use in renal stones.
Topiramate Drink lots of fluids/water
Vitamin D overdose
Calcium supplements
Complicated Jet
2 BPH 3
UTI Urination
4 Antidiuretic hormone 5 Anticholinergics 6 Finasteride
7 Imipramine
Bedwetti ng (enuresis) in children over age 7 two therapies are approved? Imipramine and vasopressin (antidiuretic hormone).
Questions Alerts!
Common questions in pharmacy exam is to ask!
1. Photoreceptors rods are sensitive for dim light and cones cells sensitivity to daylight and colors.
2. Cornea is upper layer of eye is rate determine step in ophthalmic drops.
4) Eye disorders like conjunctivitis (red or pink eye), blepharitis, and sty (hordeolum), Age related macular degeneration, Cataract, and
glaucoma.
5. External and middle ear problems. Who should be referred? Red flags
Optic nerve from both eye merge at optic chiasm and becomes
optic tract. This optic tract connect to thalamus then goes to right and left brain. Primary visual area in occipital lobes of cerebral c
ortex.
· Cornea: In the front of the eyeball is a transparent opening known as the cornea. Rate limiting step for ophthalmic drops.
· Pupil: After light passes through the cornea, a portion of it passes through an opening known as the pupil.
· Iris: Pupil opening can be adjusted by the dilation of the iris.
· Ciliary muscles: The lens is attached to the ciliary muscles.
· Q.Ciliary gland: secrete aqueous humor.
· Retina: The inner surface of the eye is known as the retina.
· Q.Macula: Small central area of retina lining. Related to Age Related Macular Degeneration (AMD) conditions and leads to
central vision loss.
· Optic nerve: The network of nerve cells is bundled together to form the optic nerve on the very back of the eyeball.
· Q.Optic disk (blind spot): The nerve cells are bundled at very back of eyeball is also known as blind spot. Rods and cones
are NOT present on the optic disk, therefore blind spot.
· Q.Myopia: If the incoming light from a far away object focuses before it gets to the back of the eye, that eye’s refractive error
is called “myopia” (nearsightedness).
· Hyperopia: If incoming light from something far away has not focused by the time it reaches the back of the eye, that eye’s
refractive error is “hyperopia” (farsightedness).
· Vitreous humor: In posterior chamber Gel like fluid filled between retina and lens.
· Q. Aqueous humor: Fluid Filled between cornea and lens. Aqueous humor flow from the ciliary body into the anterior
chamber out through a spongy tissue at from the eye called trabecular meshwork and into drainage canal. Glaucoma is
characterised by high intraocular pressure in aque- ous humor.
· Retinal detachment: Occurs due to inflammation, vascular abnormalities or injury, diabetes or in cataract surgery.
· Optic nerve: A cranial nerve II, is paired cranial nerve that transmits visual information from retina to the brain. Optic nerve is
composed of retinal ganglion cell axons and glial cells.
Dioptre
Q.A diopter is a unit of measurement of the power of lens. The total optical power of the relaxed eye is approximately 60
diopters. Diopter lenses are prescribed for reading.
Retina
Retina has 3 cell types, photoreceptor cells (rods & cones), bipolar cells, and ganglion cells.
Retinal bipolar cells: Bipolar cells exist between photoreceptor and ganglionic cells. They act directly or indi- rectly
to transmit signals from the photoreceptors to ganglionic cells.
Retina cell signalling
Dark: Photoreceptor are depolarized and release glutamate, which activates bipolar cells (an inhibitory
cells) thus bipolar cells inhibit ganglion cells.
Light: Light cause photoreceptor to hyperpolarize which inhibits bipolar cells thus activate ganglion cell.
Photoreceptors
The retina contains two types of photoreceptors, rods and cones. The rods are responsible for night vi- sion, our most
sensitive motion detection, and our peripheral vision. The rods are more numerous, some 120 million, and are more
sensitive than the cones. However, they are not sensitive to color. The 6 to
7 million cones provide the eye's color sensitivity and they are much more concentrated in the central yel- low spot
known as the macula. The image forms in eye at retina.
RODS CONE
Rhod”opsin” (retinal) Iod”opsin”
Q. Rhodopsin is rod cells pigmenta- tion. Responsible for Iodopsin is retinal cone cells responsible for day light vision color vision
dim light vi- sion.
More sensitive in dark Less sensitive in dark. Sensitive to colors.
Higher in number Less in number
Carotenoids
QAlerts!
1) More sensitive photoreceptors for dim light in eye? Rods
2) Color sensitive photoreceptors are? cones
3) Rhodopsin is red photosensitive pigment in the retinal "rods" important vision in dim light.
4) Iodopsin is pigment present in the retinal “cones” important in daylight.
5) What arteries supply blood to eye? External carotid arteries.
6. Vitamin A deficiency cause? Night blindness
7. What is precursor of vitamin A? carotenoids
GLAUCOMA
Glaucoma is chronic condition occurs due to high intraocular pressure, and can lead to blindness.
Normal range intraocular pressure or ocular hypertension 12 to 22 mm Hg (>22 mm Hg á risk of dam- age to optic fiber). Due to
angle closure increasing intra ocular pressure (IOP) cause glaucoma. This is due to;
· Increase aqueous humor production cause increase IOP.
· Decrease aqueous humor secretion (out flow) from shlemn canal.
· Q. Aqueous humor is present in anterior eye chamber. Aqueous humor is secreted from ciliary tis- sue (ciliary gland).
· Q. Vitreous humor is present in posterior eye chamber.
OPEN ANGLE GLOUCOMA CLOSED ANGLE GLOUCOMA
CUASED BY SLOW BLOCKADE OF SCHLEM CANAL CUASED BY SLOW BLOCKADE OF SCHLEM CANAL
Q. WIDE AND OPEN ANGLE BETWEEN IRIS Closure angle glaucoma between iris and cornea.
AND cornea.
MOST COMMON 90% OR MORE Less common
FIRST LINE: PG ANALOGUES, BBs FIRST LINE: PG ANALOGUES, BBs
Glaucoma is disease of the eye characterized by increased intraocular pressure resulting in damage to the optic nerve and
the retina. It can lead to blindness if left untreated.
Glaucoma investigations: Automated perimetry, Optic disc photography, Evaluation of central corneal thickness, Optic disc
and retinal imaging.
Treatment of glaucoma
There are 5 class of medications beta blockers, prostaglandin analogs, carbonic anhydrase inhibitors, alpha2 agonist
and cholinergic agonist.
Glaucoma treatment Mechanism Tips
Beta blockers Q. ↓ IOP by inhibiting for- Ist line
Timolol, mation of aqueous humor.
Betaxolol,
Levobunolol
Prostaglandin analogues "prost" ↓IOP by increase outflow of aqueous Ist line
humor through uveo- scleral pathway.
PGF2a
latanoprost, bimatoprost,
latanoprostene, travoprost
Carbonic anhydrase (CA) inhib- itors ↓IOP by inhibiting enzyme that involved in
Acetazolamide (po, formation of aqueous humor.
iv), Dorzolamide, Brinzolamide
Alpha2 agonist Dual action reduces intraocular
Brimonidine pressure inhibiting production
apraclonidine and increasing uveoscleral out-
flow.
Alpha2 agonist: (Brimonidine, apraclonidine): Dual action reduces intraocular pressure inhibiting pro- duction and
increasing uveoscleral outflow. It has peak ocular hypotensive effect occurs 2 hours after post dosing. The
topical gel reduced erythema through direct vasoconstriction.
Cholinergic agonist (Pilocarpine, carbachol): Directly stimulate muscarinic receptors to contract ciliary muscle and
increase trabecular outflow.
QAlerts!
A pregnant diagnosed with open angle glaucoma. Which of the following medication is NOT recom- mended for the
treatment of glaucoma? “prost”
Which drugs promote uterus contraction should be avoided in pregnancy?
A 45 year old with asthma for the past 5 years and currently using salbutamol, fluticasone inhalers.
Now diagnosed with open angle glaucoma. Which of the following is the first line therapy of OAG? “prost”
Age related macular degeneration (AMD)
It is two types;
Dry AMD: This is characterized by drusen means white to yellow spots in the central retina. May or may not cause
vision loss.
Wet AMD: Caused by presence of choroidal neovascular membrane (CNM). This is common cause of severe central
vision loss.
The Amsler grid or chart is useful for detecting vision changes by patients. This chart consists of
grid with straight lines and even lines. If patient see dark spot in the center of the grid or lines appear wavy, should see
the ophthalmologist.
Q. Multivitamins without carotenoids are used prophylaxis of AMD (avoid carotenoids in AMD).
Q. Lutein & Zexanthin are two types of carotenoids analogs, which are yellow to red pigments found widely
in vegetable. Lutein is precursor of zexanthine.
Carotenoid analogs may contain in multivitamin that are used for AMD prophylaxis (VITALUX-
S). Smoking is the major risk factor for AMD.
Wet AMD treatment
VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) INHIBITOR: Bevacizumab, ranibi-
zumab, and Pegaptanib. Used for the treatment of AMD.
QAlerts!
Patient with dry and wet Age related macular disorder will receive prophylaxis of? Multivitamins Multivitamin containing carot
enoids can increase risk of? cancer
Cataract
Cloudy or opaque cataracts on the lens of the eye are generally caused by a major lens Q.protein crystalline dena- turisation. In
cataracts less light reaches the retina and thus impairs vision.
Preventing Cataract:
· Avoid using corticosteroid for long duration.
· Quit smoking
· Q.Use sun glasses.
Post cataract complications includes infection, glaucoma, inflammation.
When the eye lens becomes cloudy, decrease acuity, and no pain, and this obstruct the vision is referred as cata- ract.
The most common cause of cataract is aging, diabetes, trauma, congenital diseases. Long term use of
cortico- steroids and cataract may progress even after stopping steroids.
Cataract surgery postoperative care antibiotics, dilators and anti-inflammatory drugs.
Antibiotics: Fluoroquinolones 7-10 d (besifloxacin, ciprofloxacin, gatifloxacin, moxifloxacin and oflox- acin).
Aminoglycosides 7-10 d. Gentamicin, neomycin, tobramycin
If lens capsule broken during cataract surgery, use oral ciprofloxacin or ofloxacin.
Dilators and cycloplegic: used to keep iris away from implant during early healing period and improve comfort by decrease
ciliary muscle spasm.
Cyclopentolate, phenylephrine, tropicamide.
Anti-inflammatory 3-4 wks: Dexamethasone, prednisolone, diclofenac, and ketorolac. Combination eye drops:
Tobradex (tobramycin+ dexamethasone) ointment and suspension eye drops.
Instilling Eye drops
Instilling Technique Tilt head backward, place drop in conjunctiva sac; Q. put gentle pressure on inner cantus (to
Eye drops prevent systemic absorption of eye drops).
Terms: OD = OS = OU =
QAlerts!
What is incorrect about instilling eye drops? Tilt head forward
To improve of absorption eye drops? After instilling eye drop close eyes for 2-3
min To prevent systemic side effects of eye drops? Put gentle pressure on inner cantus.
How much time to wait for second drop? Separate 5-10 minutes between 2 eye
drops If patient instilling ointment and drops, which goes first and why ? drops first
if antibiotic eyedrop and anti-inflammatory eyedrops are instilled. which one should instill first and
what time interval? Antibiotic
What is incorrect statement about cataract prevention? Using steroids helps
Ear Conditions
Outer ear, middle ear and inner ear
OTITIS EXTERNA (outer ear) OTITIS MEDIA (middle ear) Inner ear
Two common problems associated with outer Infection of middle ear cavity and the most infection of Noise, drug exposure, such as
ear swimmers’ ear childhood.
(otitis externa) and earwax builds up. Symptoms include acute ear pain often 1 ear and develop ASA, ototoxic drug,
over few hours, fever and reduce hearing. vestibular toxicities
Swimmers Ears Q. Require referral to physician. and Q. Vertigo,
Q. Self-treated by non-prescription. Symptoms
should be significantly re- duced by day 3 Common cause of middle ear infection are Meniere’s disease.
of therapy. S. pneumonia, M. catarrhalis, H. influenza.
Q. Refer if: fever & severe pain and that are
not diminished by OTC pain medi- cations. First line antibiotics amoxicillin, azithro- mycin
Most common cause external ear
infec- tion is P. aeruginosa.
Ciprofolaxacin.
car- bamide peroxide and mineral oil.
Otitis externa (outer ear)
Swimmer’s ear
Eczematous otitis externa: Drainage resulting from mild otitis externa may be self treated. Q. Ear
pain associated with ear drainage; the patient should be referred to a physician.
Otitis media
Q. Otitis media with perforation of the tympanic membrane or drainage from the middle ear, the patient should be
referred to a physician.
Drugs that cause ototoxicity’s: Aminoglycosides (can cause permanent hearing loss), furosemide, Acetyl salicylic acid,
ibuprofen, acetaminophen, cisplatin and carboplatin.
QAlerts!
3 years old has ear discharge, what is the correct step you have
place. Terms: AD = AS = AU =
QAlerts!
How to instill ear drop in 8 years old child? Pull ear up and back
Dental anatomy and physiology
·There are 20 primary teeth and 28 to 32 permanent teeth. The last 4 is being wisdom teeth.
· In adult, there are 16 teeth in maxilla and 16 in the jaw.
·Wisdom teeth may or may not grow in.
·Incisors 8, canine 4, premolar 8, molar 8. Q. Wisdom tooth (third molar) 4 of 32 teeth’s.
· Baby teeth start to grow during intrauterine first trimester (8 weeks).
· Teeth are made of enamel, dentin, and cement. Dentin composes most of the root.
· Crown is covered by the enamel.
· The root embedded inside the maxilla and jaw bones has a bulb canal.
· The bulb canal contains blood supply and nerve terminals.
· The root teeth may be single in number or multiple.
· Gingival or gums consist of mucosal tissue lies over the alveolar bone.
· Plaque is yellow sticky films that form on the teeth and gums.
· Bacteria in plaque release acid that harm the enamel.
· Brushing and flossing daily the teeth will prevent tartar forming.
· Q. Fluorides are a primary protector against dental cavities.
· Fluorides make teeth surface more resistant to acids.
· Drinking water contains enough fluorides.
1 Optic disk 2 Rods 3 Cone
The retina contains two types of photoreceptors, rods and cones. (True/False)
These rods are responsible for night vision, our most sensitive motion detection, and our peripheral vision.
(True/False)
The rods are more numerous, some 120 million, and are more sensitive than the cones. However, they are NOT
sensitive to color. (True/False)
The 6 to 7 million cones provide the eye's color sensitivity and they are much more concentrated in the central yellow
spot known as the macula. (True/False)
Cones are sensitive to color vision (True/False
Blood and Anemia: Blood cells such as platelets, red blood cells, and white blood cells
Hemostasis
· Morphological changes of anemia. Iron deficient microcytic anemia and megaloblastic anemia.
· Elemental iron supplements (ferrous fumarate > dried ferrous sulfate > ferrous sulfate>ferrous gluconate).
· Iron supplement drug interactions, thyroid hormone, tetracycline and
quinolones, cholestyramine.
Function of blood include transportation of gases, nutrients, hormones, metabolic wastes
regulates body temperature, pH, electrolyte balance, fluid volume protects, prevents blood
loss (clotting), and prevents infection (WBC and antibodies).
QAlerts!
1) The highest number of blood cells? rbc
2) The second highest number of cell? platelet
3) Reticulocytes are? immature RBC
4) Life of thrombocytes (platelets)? 7days
5) Life of erythrocytes (RBC)? 120 days
Myelosuppression is? â RBC and Leukocytes. Thrombocytes
Blood composition includes 55% of fluid which contain water, salts, proteins, antibodies, hormones, electrolytes, fats, lipids,
minerals and vitamins. The rest 45% are blood cells such as RBC 5-6 mil/mL (44%), leukocytes + platelets (1%)
Blood proteins
The blood proteins (Q. albumin, glycoprotein (globulins), and fibrinogen). Albumin is the
most common blood proteins (55%) in blood. Which is carrier of, buffer, osmotic pressure, transport lipids, fatty acids and
acidic drugs. Globulins carry ions, hormones, and steroids and bind base drugs.
Fibrinogen changes to fibrin, helps in blood clotting.
Electrolytes
The Electrolytes present in blood are Na+ , K + , Ca2+ , Mg 2+ , Cl- and CO3. Extracellular ion Na +, Cl - and Ca2+ .
· The most common extra cellular cation is sodium (Na).
· The most common extra cellular anion is chloride (Cl).
· Intracellular ions K +, Mg 2+ and phosphate.
· Antibodies (Immunoglobulin) IgG, IgM, IgE, IgA, and IgD.
Erythrocytes (Red blood cells)
RBC is composed of globin (protein), iron (metal), phospholipid (lipids), potassium phosphate (salt), hemoglobin (contain
porphyrin ring system) bind loosely to oxygen and carbon dioxide. In the overdose of carbon monoxide, the hemoglobin
binds with carbon monoxide.
Erythropoiesis is process of producing red blood cells in bone marrow. This process depends on various
factors, mainly Q. erythropoietin’s (EPO) which is an endocrine hormone produced in the kidney by the cells that
sense the inadequate tissue oxygenation. Once hypoxia is sensed, EPO produced and travel to bone marrow.
Erythropoietin, a glycoprotein is a key hormone for the production of RBC. In the absence of erythropoietin. Hypoxia is unable to
stimulate the production of RBC. The kidney is a principal organ for the synthesis of erythropoietin; therefore, kidney
failure would result in severe anemia.
Q. Chronic kidney disease anemia is caused by the inadequate production of erythropoietin (EPO).
Erythrocytes are originated in sequence of cells hemocytoblastà Megaloblasticà Erythroblast (normoblast) -->
Q. Reticulocytesà Erythrocytes.
Reticulocytes: Precursor of RBC or immature RBCs.
RBC destruction: Life span of RBC is 120 days (4 months). RBCs are destroyed in the spleen (spleen also referred to
as "grave yard" of RBC).
Erythropoietic stimulating agents
Pharmacologic stimulation of RBC production using erythropoiesis stimulating agents (ESA) such as Q. Epoeitin alpha
(Eprex), and Darbepoetin alpha (Aranesp). Used in chronic renal failure, cancer chemotherapy, HIV, hepatitis C patient
receiving ribavirin.
Q. Iron must be administered with ESA therapy to avoid depletion.
hemoglobin (Hgb)
Red Blood cell protein-containing iron metal carries oxygen in blood. The protein portion of hemoglobin is globin.
Hemoglobin content 14.5 g/100 ml. Hemoglobin consists of porphyrin ring. Oxygen binds with
porphyrin ring. Q. Porphyrin ring present in haemoglobin is tetramer. The metabolic degradation of hemoglobin
takes place principally in the reticuloendothelial system (endoplasmic reticulum).
The non-protein portion of hemoglobin is a "ferrous" complex of porphyrin. The O 2 binds the Q. ferrous form (Fe 2+ ) of iron
present in hemoglobin to form oxyhemoglobin. One O 2 is carried by each heme fraction of
the hemoglobin molecule. During this process one electron is transferred (Ferrous = Fe2+; Ferric = Fe 3+ ).
Methemoglobinemia: Q. Abnormal state of hemoglobin contains oxidized iron as ferric Fe 3+ . Iron absorbed from upper
small intestine mainly as ferrous (Fe 2+) form attached to amino acids and sugars. Iron is readily taken up the non-
absorbable form of Fe 3+ but low pH in the stomach helps to preserve it in the ferrous form.
Q. Hemochromatosis: It is characterized by excessive absorption of iron from small intestine.
Glycine is an amino acid is precursor of hemoglobin. Heme is formed under the control of enzyme amino levulinic acid syn
thetase by condensation of glycine and succinyl coenzyme A.
Myoglobin
Protein present in tissues, which is essential for oxygen transport in tissues. Carries oxygen in tissue. The porphyrin ring present
in myoglobin is monomer.
Methemoglobin: Nitrite ions react with hemoglobin and produce methemoglobin, which has a low affi nity
for oxygen and a high affinity for cyanide ions. This forms iron CN complex; it is referred as cyanmethemoglobin.
Death due to cyanide poisoning results from cyanide binding to hemoglobin, myoglobin and inhibiting cytochrome oxidase.
HEMOGLOBIN MYOGLOBIN CYTOCHROME OXIDASE
Transport oxygen in blood Transport oxygen in tissue Catalyzes phase I metabolism
Porphyrin tetramer Porphyrin monomer Porphyrin
Has affinity and binds Has affinity and binds Has affinity and binds with O2, CO, CO2 and CN.
with O2, CO, CO2 and CN. with O2, CO, CO2 and CN.
Ferrous ion (Fe2+) Ferrous ion (Fe2+) Ferrous ion (Fe2+)
Q. Carboxyhemoglobin: Carbon monoxide bound hemoglobin.
QAlerts!
What blood proteins have affi nity and bind with carbon monoxide? Hemoglobin, myoglobin
and cytochrome oxidase.
Platelets (Thrombocytes)
Platelets are referred to as thrombocytes. Platelets help in the process of blood clotting. Platelets lack nuclei and platelets are
produced in bone marrow. Q. Platelet life span is 7 to 10 days. Range in blood 150,000 to 300,000 mm3 . Deficiency of platelets
is referred as thrombocytopenia.
Granulocytes are neutrophils, eosinophils, and basophils, cells that stain.
· Neutrophils gives stain with acidic or basic dyes
· Eosinophils gives stain with acidic dye
· Basophils gives stain with basic dye
Agranulocytes; Cells that do not stain are agranulocytes. There are 2 types of cells lymphocytes and monocytes.
Rh factor
Agglutinogens in human RBCs are known as the Rh factor blood with this factor is described as Rh +ve (90% of
population). Blood without this factor is described as Rh (-) negative. In Rh-negative mother, Rh-positive antigens may
transfer from Rh-positive fetuses to the mother via placenta. This may lead to production of Rh-positive antibodies in the
mother’s blood. These same antibodies may transfer back from the mother’s blood into fetus via the placenta, and
produce antigen antibody reactions. This leads to lysis of red blood cells in the fetus, and miscarriage. Rhogam prevents
the formation of anti-Rh antibodies in a mother who bears Rh positive fetus.
Q. Rh-ve women who have +ve babies get a Rhogam shot.
QAlerts!
Who will get RhoGAM vaccine? Rh-ve women who have +ve babies get a Rhogam shot.
Blood Groups
Surface of RBC's have antigen.
Group A RBC has A antigen, plasma has B antibodies. Group B has B antigen, A antibodies.
Group AB has A and B antigens, no antibodies.
Q. Group O (universal donor) has no antigens, has antibodies against A and B, transfusion reaction can lead to kidney failure.
Blood Type Donate blood to Receive blood from
A+ A+ AB+ A+ A- O+ O-
B+ B+ AB+ B+ B- O+ O-
AB+ AB+ Q. Everyone (universal receiver
)
O+ O+ A+ B+ AB+ O+ O-
A- A+ A- AB+ AB- A- O-
B- B+ B- AB+ AB- B- O-
O- Q. Everyone (universal donor) O-
AB- AB+ AB- AB- A- B- O-
QAlerts!
What blood group can be given to anyone? A. O B. O- C. O+
Qualities of blood
Temperature: 38 o C (100.4 o F), heparin (anticoagulant) added in blood storage. Viscosity: 5xH 2 O sticky, cohesive, and resistant to
flow pH 7.35 to 7.45 volume: 4 to 6 litres (7% body weight in kg) (2.2 lb/kg).
Transport O 2 and CO 2 2% of cells in whole blood males: Age 40-54 (androgens stimulate production cells) females: 37-
47 (estrogens inhibit production of cells).
Hemoglobin (Hb): binds transport O 2 and CO 2 (280 million/RBC) Hemoglobin - Fe +2 males: 14 to 18 g/100ml; females: 12 to 16
g/dl, fetal hemoglobin has a higher affinity for O 2 .
Anemia has categorized based on morphological changes of RBC.
Morphological change Microcytic (hypochromic ↓ iron Macrocytic (megaloblastic)
Normocytic (Normochromic) (Sickle cell disease
s ) (↓ vit. B12 or folate)
)
MCV ↓ ↑ No change
*TIBC: Total Iron Binding Capacity
Mean cell volume (MCV): The MCV detects changes in cell size. Decrease in (↓) MCV indicates a microcytic cell
anemia, which is due to iron deficiency. Increase in (↑) MCV indicates macrocytic anemia (megaloblastic anemia),
which is due to deficiency of vitamin B 12 and folic acid.
Mean cell hemoglobin concentration (MCHC): Weight of hemoglobin in average red blood cell. In microcytic anemia decrea
se in (↓) MCHC. This is not significant in determining megaloblastic anemia.
Total iron binding capacity (TIBC): Increased in microcytic anemia.
QAlerts!
Microcytic anemia all labs decrease, except? TIBC, and free transferrin.
Transferrin
Q. FREE Fe 2+ circulates binds transferrin and transports it from small intestine to its storage sites in the liver
and from the liver to the bone marrow for the synthesis of hemoglobin.
Hematocrit (Hct)
This is ratio of the volume of RBC to volume of whole blood. A reduction in hematocrit or RBC count can also be used to
define anemia.
Serum ferritin
Q. The major iron storage in protein in blood. Serum ferritin <30 ng/mL is anemia. Pregnancy <50
ng/ml. Normal range of serum ferritin is 20 to 250 ng/mL for men and 10 to 120 ng/mL for women.
Iron storage is measured by serum ferritin (the concentration of ferritin is proportional to iron stores).
Serum ferritin levels are the screening test for iron deficiency anemia.
hemoglobin (Hgb)
Anemia is most commonly defined as reduction in hemoglobin concentration. Q. Typically, based on these normal
ranges, Hb of <130 g/L defines anemia in men and Hb <120 g/L defines anemia in non- pregnant women.
Microcytic (hypochromic) anemia
Symptom’s fatigue or dyspnea on exertion may occur during pregnancy and in infants. Mainly occurs due to
iron deficiency.
NON-HEME TIPS
Ferrous fumarate Recommended daily Q. Ferrous fumarate
dose 100 salt
33%; 100 mg Fe/300 mg mg Elemental iron. with highest element
Ferrous sulfate Ferrous fumarate 100 al iron Fe2+
mg = 33 mg of Fe.
20% 60 mg Fe/300 mg
Side effects: Most
Ferrous gluconate 12% 35 common constipation. .
Q Iron ↓ absorption by
mg Fe/300 mg
food and antacids, Ca,
Mg, Al, levodopa, Iron polysaccharide
Polysaccharide-iron complex (Fera- methyldopa, tetracycli complex. 100%
MAX) ne, elemental iron
(150 mg Fe/150 mg) NaHCO3, separate admi FeraMax: Highest GI
n by 2 hr. absorption.
Approved in patient
Separate with
thyroxin CKD on hemodialysis
& quinolon
es
and bisphos
phonates.
Iron dextran inj. IM or IV 50 mg Fe/mL Anaphylactic
reactions
are reported.
Iron base suspension
HEME IRON
100% elemental iron
Heme-iron
Polypeptide (Proferrin)
Iron supplements are regulated as schedule 2 drugs (behind the counter). Iron containing <30 mg dose is schedule III (over
the counter).
Factors alters iron absorption
· Food decrease iron absorption thus iron given on Q empty stomach. Coadministration with vitamin C (ascorbic
acid) 250 mg) enhances non-heme iron absorption. Whereas polyphenols, and naphtates found in tea and coffee
can inhibit non-heme iron absorption.
· The most common side effect of iron supplement is constipation. Take with food to decrease GI side effects like
constipation, nausea and epigastric pain. However, absorption is better on empty stomach.
Enteric coated and time released iron preparation is intended to reduce side effects but may
be ineffective because of failure to release iron in the gastric environment.
Q The usual target dose is 105-120 mg/day elemental iron in TID divided. To begin iron
store, replenish may take 6 to 9 mo and can be monitored by measuring serum ferritin.
Parenteral iron is reserved for patients with malabsorption or true intolerance to oral iron
therapy. Food rich in heme iron is liver, lean red meats, seafood (oysters, clams, salmon, sardine, and shrimp).
Q. Antidote for iron overdose is deferoxamine. Mechanism of deferoxamine act by chelation. The overdose of iron can cause
hemochromatosis and this can be treated by deferoxamine.
QAlerts!
Iron salt with highest elemental iron is? Ferrous fumarate
Iron salt most common side effect constipation can be minimized by? Take with food
Iron and drug-drug interactions? Levothyroxine, fluroquinolone, tetracycline, bisphosphonates, PPI
Iron absorption is increased by? Vitamin
C Iron overdose is treated by? deferoxami
ne
MEGALOBLASTIC ANEMIA (macrocytic anemia)
Megaloblastic anemia is a group anemia characterized by enlargement of red blood cells size. This condition is due
impaired DNA synthesis which inhibits nuclear division. Megaloblastic
anemia most often due to deficiency of vitamin B12 and folate which are necessary for synthesis of DNA.
Mean cell volume is increased. (MCV >100 fL)
· Q. Impaired DNA synthesis usually due to folate or vitamin B12 deficiency.
· Major causes of megaloblastic anemia chemotherapy and alcoholism and seniors.
· Drugs that causes megaloblastic anemia are acyclovir, alcohol, Q. antiepileptics (phenytoin, carbamazepine, and
valproic acid), Q. methotrexate (dose dependent), nitrofurantoin, oral contraceptives, proguanil, sulfasalazine,
trimethoprim (usually due to worsening of pre-existing folate deficiency).
Vitamin B 12 deficiency
The most frequent cause vitamin B 12 deficiency is pernicious anemia is a type of autoimmune gastric atrophy disorder. This occurs
due to Q. deficiency of intrinsic factor. The intrinsic factor helps in absorption of vitamin B 12 in stomach/ileum.
Vitamin B 12 deficiency also develops due to gastrectomy, ileal resection, Zollinger-Ellison syndrome, pancreatic insuffi ciency.
Treatment: Q. Parenteral vitamin B 12 supplement. Oral vitamin B 12 supplements are NOT effective in pernicious anemia due to
deficiency of intrinsic factor.
Q. Vitamin B 12 available as oral, im/sc 100 mcg daily for 1 wk or 200 mcg weekly sc/im until Hgb normalized. The
daily requirement of cyanocobalamin or hydroxocobalamin 6-9 mcg. Vitamin B 12 only nutrient need gastric secretion (intrinsic
factor) to be absorbed from GIT.
Vitamin B 12 deficiency cause enlargement of bone marrow, RBCs, WBCs and platelets. It affects all proliferating cells.
Q. SCHILLING TEST: To detect pernicious anemia that caused by deficiency of vitamin B 12 . Urinary excretion test is
used to diagnose
deficiency of vitamin B 12 caused by decreased vitamin B 12 absorption (lack of intrinsic factor causes pernicious anemia).
Folate Deficiency
Q. The most often occurs in chronic alcoholics, pregnancy and drug induced folic acid deficiency by drugs such as
antiepileptic drugs carbamazepine, phenytoin, sulfonamides, methotrexate,
dapsone, and oral contraceptives. Intestinal malabsorption caused by Giardia lamblia infection.
Folic acid (folate) supplements:
The daily requirement is 200 mcg. For therapy 1 mg, 5 mg is used.
Patient taking methotrexate takes folic acid 5 mg/week. Certain medical conditions like type 1 DM, seizure in
pregnancy therapy with valproic acid, carbamazepine, BMI >35 kg/m 2 , and malabsorption disorder.
QAlerts!
The most common cause folic acid deficiency is? diet, drugs and alcoholism.
Oral folic acid supplements recommended at childbearing age to decrease neural tubule defects. The common source of
vitamin B 12 is? meat and dairy products (can be deficient in vegans in pregnancy).
Elderly are commonly deficient in Vitamin B 12 and can cause? Megaloblastic.
Normocytic (Normochromic)
· In normocytic anemia MCV is normal.
· Due to acute hemorrhagic or RBC hemolysis due to immune or non-immune mediated.
· Examples of normocytic anemia includes aplastic, hemolytic anemia, sickle cell disease, and thalassemia.
Haemolytic anemia
The immediate cause of hemolytic anemia is destroyed faster than the bone marrow can replace them. This means that
RBC are destroyed and removed from the bloodstream before their normal lifespan is over. Hemolytic
anemia can be inherited or can develop later in life.
Sickle cell disease
Sickle cell anemia and thalassemia are hemolytic anemia associated with abnormal hemoglobin’s. The sickle cell
disease is an inherited disorder caused by a defect in the gene for hemoglobin. Due to poor solubility of such abnormal
hemoglobin in a reduced state, semi crystalline bodies are formed inside of RBC. These crystalline bodies are pointed
and elongated inside of the cell, and rupture the red blood cells.
Q. Glucose-6-phosphate dehydrogenase (G6PD) deficiency hemolytic anemia: The enzyme G6PD necessary to maintain
the reduce glutathione level (GSH) in red blood cells. Glutathione is an antioxidant, which prevents the oxidation of
hemoglobin to methemoglobin. This enzyme is necessary to prevent the hemolysis. The deficiency of this enzyme may
cause severe hemolytic anemia in patients with the use of certain oxidant drugs such as
primaquine, sulfonamide, nitrofurantoin, nalidixic acid, probenecid, chloroquine, and dimercaprol.
COOMBS TEST: The coombs test is used to distinguish immune mechanism or glucose 6-phospho dehydrogenase (G6PD)
deficiency anemia. In autoimmune hemolytic anemia, coombs test is positive. Example of drugs that cause false positive
coombs test penicillin's, cephalosporin's and methyldopa.
Aplastic anemia
Q. Total or partial destruction of the bone marrow or â ability to produce bone marrow.
â RBC = Anemia
âWBC = risk of infections
âPlatelets = bleeding risk
Aplastic anemia is due to inadequate production or release of myeloid stem cells.
Drugs that cause cell aplasia: Azathioprine, phenytoin, isoniazid, penicillamine, chlorpropamide, chloramphenicol,
erythropoietin, cephalosporin's, penicillin's, tetracycline's, insulin. Methotrexate, isoniazid, quinidine, quinine,
rifampicin, sulphonylureas, methyldopa, mefenamic acid, drugs with oxidant effect on cell membrane
(particularly in G6PD deficiency).
Agranulocytosis
Q. Agranulocytosis is profound reduction of blood cells such as neutrophil, this
can cause symptoms like fever, mouth, throat ulcers and this can lead to prostration and
death. Recovery usually 2 to 3 weeks after the drug is withdrawn. Repeat exposure to causative drug is not
recommended due to sensitization.
Drugs that can cause agranulocytosis: Antibiotics (penicillin's, cephalosporin's, cotrimoxazole, chloramphenicol,
sulphonamides), antidepressants (imipramine, clomipramine, desipramine), antiepileptics (carbamazepine, phenytoin),
anti-inflammatory (gold, penicillamine,
leflunomide, sulfasalazine, NSAIDs), antipsychotics (chlorpromazine, thioridazine, Q. clozapine), antithyroid drugs (methima
zole, propylthiouracil), captopril, procainamide, and Q. ticlopidine.
QAlerts!
What antipsychotic drug use is limited due to its serious side effects of agranulocytosis? clozapine Patient using clozapine sh
ould be monitored for? WBC or CBC
Thrombocytopenia
Reduced platelets to less than 150 x 10 9 /L). May present as easy bleeding, bruising or purpura. Prolong bleeding time but
INR remains normal. Usually occurs 7 to 10 days after drug administered. Examples drugs cause thrombocytopenia side
effects are antibiotics penicillin’s, vancomycin, cotrimoxazole, rifampin. NSAIDs, acetaminophen, Amiodarone,
carbamazepine, valproic acid, phenytoin, haloperidol, ranitidine, simvastatin. Q. Heparin induced thrombocytopenia (HIT)
is associated with heparin and LMWH (Enoxaparin, Dalteparin, Tinzaparin, Nadroparin)
1. Serum Ferritin 2. Anemia associated chronic renal disease 3. Parietal cells in stomach
19. Microcytic anemia 20. Sickle cell anemia 21. Folic acid
28. Bronze disease, excessive absorption and storage of iron 29. Deferoxamine 30. Erythropoietin’s
Biochemistry.
Catabolism: This pathway converts pyruvate (glycolysis), acetyl Co-A (fatty acid degradation)
and amino acid to carbon dioxide and water with release of energy. This cycle is strictly oxygen dependent (aer
obic). Catabolism examples include glycogenolysis and glycolysis.
Anabolism: This pathway forms amino acid such as aspartate and glutamate from cycle intermediates also the
porphyrin ring of the heme (hemoglobin, myoglobin and cytochrome) is formed from intermediates cycle.
Anabolism examples include glycogenesis and gluconeogenesis.
Fermentation: The formation of ethanol and lactate from glucose are examples of fermentation.
Carbohydrates Carbohydrate digestion and absorption: Dietary carbohydrate is digested in the mouth and intestine and a
Glycolysis
Glucose + O2 à CO 2 + H 2 O + 2 ATP
Glycolysis is breakdown of glucose to water and carbon dioxide. Glycolysis occurs in the cytosol
and mitochondria in most organs of the body. Glucose utilization pathways can yield energy and diverse biochemical tra
ffic. Cellular respiration
Metabolic reactions that take place in the cells of organisms, in which oxygen molecules or
nutrients converted to chemical energy such as adenosine triphosphate (ATP) and then release waste
product. This process occurs in catabolic reactions.
Cytosolic process
Mitochondrial Process
Under anaerobic conditions (absence of O2 ): Glycolysis involves the conversion of glucose to lactate (lactic acid).
Q. This can occur in cells without mitochondria.
Under aerobic conditions (presence of O 2 ): Q. Glycolysis involves the conversion of glucose to pyruvate
(pyruvic acid), this occurs in mitochondria.
Gluconeogenesis
Q. Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources in liver.
Proteins and fats-------------------- > glucose in liver
Liver, kidney
Fatty acids à Acetyl CoA à pyruvate -------------àglucose-6-phosphate------------ à glucose
Amino acids à Acetyl CoA à pyruvate -------------àglucose-6-phosphate------------ à glucose
This process, which occurs primarily in the liver and kidney, is the synthesis of glucose from small non- ca
rbohydrate precursors such as lactate and alanine.
Protein metabolism
PROTEIN CATABOLISM:
PROTEINS à PEPTIDES + AMINOACIDS----------------- à NH3 à Urea à Urine
DEAMINATION
Q. Enzymes that breakdown proteins to amino acids are proteases.
ACIDS AMINO
The amino acids from proteins are precursor of compounds and energy source like converted to acetyl
CoA. Amino acids degradation eliminated -NH2 - group and this converts to NH 3 and this may be toxic.
Ammonia eliminates through conversion of urea in animals. The NH 2 group is removed by transamination and
oxidative deamination to urea.
NH3 -CH2-COOH
UREA CYCLE
Aminotransferases
Dietary proteins à Amino acid-------------------------------- à NH 3 à Urea à Urine
Glutamate dehydrogenase
Urea is formed from NH 3 and amino (NH2 ) group of Asp bicarbonate (HCO3 ) in urea cycle in liver. Five enzymes
involved in urea cycle, two enzymes are in mitochondria and three enzymes involved in cytosol, thereby the
urea cycle partially occurs in mitochondria and partially in cytosol.
Ammonia (NH3 ) is produced in all tissue, but the urea cycle is only carried out in liver. Thus, NH3 must be
transported to liver with non-toxic form. Q. NH3 is converted to glutamine (Gln) which is not toxic.
20 amino acids are converted to 7 common intermediates. Those are:
Alanine, Cysteine, Glycine, Serine, and Threonine are Pyruvate glucogenic and ketogenic intermediate
degraded to Pyruvate
Q Acetyl-CoA. Acetoacetate Ketogenic intermediates(form ketone bodies).
QAlert!
Urea cycle occurs in? liver
Non toxic form ammonia is? glutamine
Ketogenesis or fatty acids oxidation
It occurs when there is a high rate of fatty acid oxidation in the liver. Three types of substances Q. beta hydroxy
butyric acid (80%), acetoacetic acid (20%) and acetone (trace amounts). These three substances
are collectively known as the ketone bodies (also called acetone bodies or acetone). Enzymes responsible for ketone bo
dies formation are associated with mitochondria.
Adipose tissue Blood Liver
Beta oxidation
Lipolysis
FFA= Free fatty acids
QAlerts!
The major ketone produced in ketogenesis is? Beta hydroxybutyric acid
Amnio acid biosynthesis
Amino acids are not only making proteins and also precursor of severs products such
as neurotransmitters (dopamine, nor epinephrine and epinephrine), hormones, and porphyrins.
Amino acids synthesis
QAlerts!
Enzymes catalyze levodopa to dopamine? Dopa
decarboxylase. Enzyme catalyze norepinephrine to epinephrine? N-
methyltransferase Sympathetic neurotransmitters? Norepinephrine
and epinephrine Examples of vasopressors? Norepinephrine and
epinephrine
Tyrosine à Thyroxine (thyroid hormone).
Tyrosine à Catalyzation by tyrosinase give phenyl 3-4 quinone than polymerization
gives melanin (black skin pigment).
Q. Tryptophan à 5-hydroxy tryptophan à 5-hydroxy tryptamine (5HT or
serotonin). Tryptophan à niacin (vitamin B3 ).
QAlerts!
Stepwise formation of serotonin from tryptophan? 1. Hydroxylation 2.
decarboxylation Serotonin has? Indole ring
Histidine àhistamine; decarboxylase of histidine produces histamine
QAlerts!
Histidine decarboxylation produce? histamine
Q. Arginine à Nitric oxide (NO) (vasodilator) Arginine à Urea Arginine à Creatinine Q. Glutamate à Gamma amino
butyric acid (GABA neurotransmitter) by glutamate decarboxylase
Q. Essential amino acids Non-essential amino acids
Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threon Alanine,
ine, Tryptophan, and Valine asparagine, Cysteine, Gluta
Arginine and histidine are essential in infants only. mate, Glutamine,
Glycine, Proline, Serine and
Tyrosine
Arginine although it is produced but most degrade to urea. Histidine and arginine is essential for infants.
mnemonic"PVT TIM HALL"
Nitric oxide is produced from? arginin
Proteins structure:Proteins composed of amino acids. Proteins are formed by condensation of amino acid. Structural
role within the cell and also within the connective tissue and skeleton of the whole organism.
Secondary structure :Occurs with hydrogen bonds forming between the carboxyl portion of amino acids and the amino
group of another. Q. Alpha helix = coiling into a helix are formed from hydrophilic aminoacidic and beta pleated sheet
= a folded sheet as polypeptide folds back on itself formed from hydrophobic amino acids both shapes contains
hydrogen bonds which stabilize amino and carboxyl group. Not all of a polypeptide forms secondary structure
in most proteins like proline is NOT found in alpha helices.
However, it can be located in the beginning and end of alpha helix.
Tertiary structure Q. Three-dimensional (3D) structure formed by disulfide (S-S) bonds of cysteine. Q. Covalent
bonds between sulfur containing amino acids, producing the three-dimensional folded structure of most
proteins. The amino acids that contain sulphides (-S-S-) bonds are cysteine and stabilize 3 dimensional structures
Q. Cysteine (cys): Disulphide bond (-S-S-); stabilizes tertiary protein structure.
Quaternary structure
A protein consisting of more than 1 amino acid chain. Separate polypeptide chains that assemble togeth
er. Allows greater regulation of transport function example hemoglobin for O 2 transport
QAlerts!
Linear chain of amino acids structure is? Primary
Cysteine amino acid pair joined by di-sulfide bond in? Tertiary
Which of the structures determine the biological function of the proteins? Tertiary
Which protein structure has more than one amino acid chain? Quaternary
1) Amino acid is linked with -CONH- peptide bond to form proteins. The linear sequence of
amino acids structure is? Primary
Types of proteins
There are 20 amino acids commonly found in proteins, they are linked together by peptide
bonds. Protein is generally classified into three different categories.
Types Functions Examples
alpha-amino acids.
Fibrillar
Proteins
Conjugated protein Conjugated proteins are further classified on the nature of their prosthetic groups.
Polypeptides + non- Example Present in
proteinaceous
Contain metal ions Fe, Co, Zn, Cu, Mg.
Metalloprotein Q. Cobalt in cyanocobalamin (vit.B12)
Glycoproteins: Q. mucins, mucoproteins (carbohydrate >10%) present blood and Oligosaccharides Antigens Enzymes
Polypeptides Carbohydrates
viscosity.
Heparins are Mucopolysaccharide
Polypeptides Lipids
Serum Lipoproteins. Lipoproteins are composed of neutral lipids
TG, cholesterol surrounded by shell of
apoproteins, phospholipids and free cholesterol.
Derived proteins: They are formed from primary or conjugated proteins by the actions of the acid, alkali, heat,
water, enzyme or alcohol. They generally differ in physical and chemical properties from the protein they are
derived from. They are subdivided into primary derived protein (denatured protein) or
secondary derived protein.
Denaturation of proteins: A protein denaturation results in the unfolding and disorganization
of the protein structure, which does not occur by hydrolysis.
Denaturising agents include: heat, organic solvents, mechanical mixing, strong acids or base, detergents
and ions of heavy metals such as lead or mercury. Denatured proteins are insoluble and precipitate.
Denaturation process is often irreversible.
QAlerts!
2) Casein? Phosphoprotein
3) Keratin is an albuminoid present in? skin, collagens, nails, cartilages
4. Mucin is type of? glycoprotein
Cell Membrane
Composed of lipid by layer with proteins embedded within the membrane.
Lipid bilayer- Phospholipids contain hydrophilic head (outer portions of membrane) and
Hydrophobic chains (inner portions of membrane).
Phospholipid bilayer has head and tail group. The tail group is hydrophobic (lipophilic) and head group is hydrophilic
means water soluble.
Fats and Lipids
Lipids can be divided into five classes according to their chemical structure fatty acyl,
Glycerolipids, Glycerophospholipids, Sterol
Types of fat Characteristics
Example FATTY ACIDS
Wax high molecular weight esters, consist of monohydric
alcohol and high molecular weight of fatty acids
Glycolipids Cerebrosides Q. Sphingosine + carbohydrate à Ceramide à Cerebroside
Triglycerides Glycerol+3 fatty acids
or Cerebrosides
Phospholipids Glycerol+2 fatty acids + phosphate + amino alcohol.
Lecithin is phospholipid
Gangliosides sphingolipids + sialic acid or choline phosphate.
Glycolipids Glycerol or sphingosine +
fatty acid+ monosaccharide
Phospholipids lecithin Glycerophospholipids and Q. SPHINGOLIPIDS. Component Q.3 cyclohexane + 1 cyclopentane fused
Steroids
of cell membrane. rings vitamin D, steroidal hormones estrogen,
progestin, bile acids, cholesterols.
Fixed oils and fat esters of glycerol and fatty
s
acids which are solid at room temperature, are know
n as fat, olive oil
lipids and Sphingolipids
GLYCOLIPIDS: Also known as cerebrosides. They are isolated from the brain. Upon hydrolysis, they yield fatty
acid, galactose and sphingosine. They are also known as galactolipids due to the presence of galactose, such
as phrenosin, and kerasin. Glycolipid metabolism takes place in cytoplasm.
Q. Cerebroside: They occur in myelin sheath of nerves and white matter of the brain tissues and cellular
membrane. Important for nerve conduction. Cerebroside are glycolipids contain b-galactose carbohydrate +
sphingosine + fatty acid but no phosphoric acid.
Phospholipids: Known as phosphatides. They are esters that consist of fatty acid, phosphoric acids and
nitrogenous compounds, such as lecithin. These are important part of membrane. Lipid bilayer; cell
membranes (phosphate layer is water soluble and lipid layer is lipid soluble).
Cerebrosides consist of? sphingosine + lipids + sugars
Gangliosides consist of? Sphingolipids + sialic acid or choline phosphate
Lipid metabolism
Catabolism triglycerides stored in fat cells are hydrolyzed by hormone, sensitive liposes into 3
fatty acids and glycerol.
Fatty acids- are broken down by B-oxidation to Acetyl CoA (2Carbon Units), which enter the Kreb cycle to
complete oxidation to CO 2 + H 2 O with release of considerable energy, too rapid breakdown of fatty
acids leads to ketone bodies (Ketogenesis) as in diabetes mellitus.
Glycerol enters glycolysis and is oxidizes to pyruvate and via the Krebs cycle to CO 2 + H 2 O.
Steroids may be converted to other compounds such as bile acids, vitamin D or steroidal hormones; they
are not broken down completely.
LIPOLYSIS LIPOLYSIS
TRIGLYCEROL ----------------à FREE FATTY ACIDS ---------à ACETYL-CoA-------- à CO 2
ACETYL CO-A------- à CHOLESTEROL
Q. HMG-CoA reductase
AcetylCoA --> B-hydroxy, B-methyl, glutaryl CoA --> --> --> Mevalonate --> Cholesterol
Essential fatty acids
Essential fatty acids (EFAs) are required in amounts equalling 6 to 10% of fat intake (equivalent to
5 to 10 g/day).
Q. Omega 3 and omega 6 fatty acids are polyunsaturated fatty acids. Meaning they contain more than 1 cis d
ouble bond
Q. They include (!)-6 (n-6) fatty acids are linoleic acid (cis-9, 12-octadecadienoic acid) and arachidonic acid (cis-5, 8,11,14-
eicosatetraenoic acid) and -3 (n-3) fatty acids are linolenic acid (cis-9, 12, 15- octadecatrienoic acid), cis-5, 8,11,14,17-
eicosapentaenoic acid (EPA), and cis-4,7,10,13,16,19- docosahexaenoic acid (DHA).
EFAs must be provided by the diet. Vegetable oils provide linoleic acid and linolenic acid, and marine fish oils
provide eicosapentaenoic acid and docosahexaenoic acid. However, some EFAs can be made from others. For example, the body
can make arachidonic acid from linoleic acid, and eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid can be partially
synthesized from linolenic acid, although fish oil is a more effi cient source.
Omega 3 à EPA à DHA Omega 6 à Arachidonic acid
Q. Fats (worst to best): Trans fats > Saturated > cholesterol > monounsaturated > polyunsaturated (Omega).
QAlerts!
Linolenic acid is? Omega-3
Omega-6 fatty acid is? Linoleic acid
How many double bonds in Omega-3 fatty acid? 3
Mnemonics: “ALA 3 word which has 3 double bond and LA is 2 words has 2 double
bond” What essential fatty acid produce omega 3?
Types of Enzymes
Enzyme are catalyst and catalyze biochemical reactions. Based on their functions or type reaction they
catalyze there are grouped in classes.
molecules without using water.
Enzyme’s suffix is “ase” Coenzyme and cofactors
Most enzymes require an additional non-protein component to carry out its catalytic function called as
cofactors. A coenzyme or metal ion that is covalently bound to the enzyme protein is called prosthetic group.
Two types of cofactors. Inorganic ions such as Fe2+, Mg2+, Zn2+ and a complex of organic molecule called coenzyme (f
unctions as transient carrier of specific functional group)
Kinases are categorized as? Transferases which transfer functional groups
Q. Basal Metabolic Rate
The basal metabolic rate (BMR) is the amount of energy per unit time that a person needs to keep the
body functioning at rest. Metabolism comprises the processes that the body needs
to function. The baseline metabolic rate of an animal is measured as basal metabolic rate.
Varies with body size
and activity
levels. Diet should be
minimum 1100 Kcal/da
y.
Balanced diet
Carbohydrate 55%.Proteins 30% Fats <5% Fibre 30 g/day (vegetables, cereals etc) Minerals/vitamins Water 8 to
10 glass/day Salt <2 g/day
Special Diets DASH diet: Dietary Approach to Stop Hypertension focuses on more vegetable, fruit and low-fat
dairy, fish, nuts, poultry and whole grain.
Keto diet: Low carbs, high fat and high proteins. May reduce frequency of seizure.
Q. Functional Foods: also known as nutraceuticals are food ingredients that offer health benefits in
addition nutrition value. Examples fortified with vitamins, minerals. Probiotics or fiber.
Some fruits and vegetable with high antioxidants.
Probiotics
“2P6T robiotics26Tare live microorganisms which, when administered in adequate amounts, confer a
health benefit on the host.
QAlerts!
Definition of functional food? Foods with nutrition and therapeutic
benefits. A patient taking psyllium daily for the 10 year to treat? Weight loss
Infant’s nutritionn
Formula milk (Q. cow milk-based formula, lactose free cow milk-based formula, soy protein isolates-
based formula, hydrolyzed protein formula, amino acid-based formula, pre-thickened formulas).
· Q. Iron fortified formula milk (birth to 6 months). Q. Functional nutrition’s:
Nutrition therapy to treat nutritional deficiencies considers every aspect of health, diet and
overall lifestyle. Eg. Glucerna.
· Vitamin D drops 400 IU/day, and not exceeds 1000 IU/day (only in children who are
on complete or partial breast feeding (human milk).
· Cow milk-based formula for higher protein content. Most formula milk resembles casein
and whey content resemble to human milk. The carbohydrate sources of cow milk lactose.
· Soy protein isolate-based formula: Free of cow milk proteins and lactose. Soy
formula contains soy isoflavones, a phytoestrogen which had been linked to reduced
reproductive function.
QAlerts!
What formulation milk is the closest to mothers milk? Cow milk based formula
At 8 months, pharmacist recommend the infant nutrition formula containing? Non- iron containing formula
milk
0WB ater soluble 1FB at soluble (ADEK)
Steatorrhea: presents with vitamin ADEK.
Q. All except BR12R and folate wash out of body easily. Fat soluble vitamins absorption depends on.
Vitamin B deficiencies can lead to diarrhea, dermatitis, and glossitis.
The presence of fat substance in GIT
Q. Limit vitamin C to not more than 60–100 mg/day as the
metabolite (oxalate) can result in kidney Q. Hepatic function (vit. K synthesised in liver)
Thiamine (Vitamin B 1 )
Derived from a substituted pyrimidine and thiazole, which are coupled by a methylene bridge. It is rapidly
converted to its active form thiamine pyrophosphate (TPP) and thiamine diphosphotransferase.
Dietary requirements: If the carbohydrate content of the diet is excessive, then thiamine
intake should be required.
Deficiency: Severely reduced capacity of cells to generate energy. Beriberi (result from a diet
of carbohydrate rich and thiamine deficiency).
CHRONIC ALCOHOL: Wernicke-Korsakoff
Q. Wernicke-Korsakoff syndrome: Thiamine related disease mostly found in chronic
syndrome
alcoholics. Deficient in chronic alcoholic thereby take vitamin BR1R supplement.
¯ VITAMIN B1: BERIBERI
Vitamin B1 = Most heat sensitive
Sources: Legumes, meat, green, fish and egg.
QAlerts!
Chronic alcoholics have deficiency of ? Thiamine
All patient receiving treatment of alcohol withdrawal or alcohol related disorders will get? thiamine We
rnicke-Korsakoff Syndrome is treated by? Thiamine
Riboflavin (Vitamin B 2 )
It is a precursor for coenzyme flavin mononucleotide (FMN) and flavin adenine dinucleotide
(FAD). The enzyme that requires FMN or FAD as cofactor is termed flavoproteins.
Riboflavin decomposes when exposed to visible light (photolabile or the light sensitive vitamin). Q. This
characteristic can lead to riboflavin deficiencies in newborns treated for hyperbilirubinemia
by phototherapy.
Source: Eggs, milk, meat, and cereals.
Dietary requirements: 1.2 to 1.7 mg/day for normal adults.
Deficiency: It is often seen in chronic alcoholics due to their poor dietetic habits.
Sign and symptoms; Glossitis, seborrhea, angular stomatitis, cheilosis and photophobia.
QAlerts!
Newborns treated for hyperbilirubinemia by phototherapy (baby incubator) will get supplementati
on of? Vitamin B2
Niacin (Vitamin B 3 )
Protein diet restriction like in renal disease patients may cause deficiency of? tryptophan and niacin
Pantothenic acid (Vitamin B 5 )
· It is formed from b-alanine and pantoic acid.
· Source: Whole grain cereals, legumes, and meat.
· Deficiency: Extremely rare for it is readily available food sources.
QAlerts!
What vitamin is pantothenic acid? Vitamin B5
Vitamin B 6 (Pyridoxine, Pyridoxal, and Pyridoxamine)
Biologically active form of vitamin BR6R, and pyridoxal phosphate.
Dietary requirements: Q. During pregnancy and lactation, the requirement for vitamin BR6R increases
approximately 0.6 mg/day. Therefore, vitamin BR6R used for nausea & vomiting in pregnancy.
Q. Drugs (¯) pyridoxal isoniazid for tuberculosis, and penicillamine (for rheumatoid
arthritis and cystinurias).
Q. Diclectin (vitamin BR6 R10 mg+ doxylamine 10 mg) is used for the treatment of nausea &
vomiting in pregnancy (morning sickness). Up to 4 tabs daily (2 bedtime, 1 in morning and 1 afternoon).
Avoid vitaminBR6R with levodopa because, vitamin BR6R increases the peripheral
conversion of levodopa to dopamine thereby it gives nausea and vomiting.
Deficiency (<10nmol/L): Peripheral neuropathy, convulsions, sideroblastic anemia,
and hyperirritability. Isoniazid therapy to treat tuberculosis may
lead to vitamin BR6R deficiency.
2) Antiemetic effect occurs at 1 -3 mg (adult), min 0.6 mg (children).
Drugs that ¯ VITAMIN BR6 Drug avoid with vitamin BR6
Q. Isoniazid use Vit. BR6R 25 mg daily to prevent Levodopa: Vit. BR6 Rconcomitant use can
peripheral neuropathy. increase nausea & vomiting side effect.
Sideroblastic anemia (iron stores in mitochondria)
and this caused by deficiency VBR6R deficiency.
!QAlerts!
Deficiency: Excessive consumption of raw eggs due to affinity of egg white protein, AVIDIN, for biotin pre
venting intestinal absorption of the biotin
. QAlerts!
Biotin is? Cofactor for enzymes that are involved in carboxylation.
Cyanocobalamin (Vitamin B 12 )
Vitamin BR12R composed of a complex tetrapyrrole ring structure (corrin ring) and a cobalt ion in the
center. It must be hydrolyzed from protein in order to be active. Hydrolysis occurs in the stomach
and carried to the ileum where it is absorbed. BR12R as cofactor during these reactions.
Following absorption, the vitamin is transported to the liver in the blood bound to
trans cobalamin II.
Deficiency: Q. Megaloblastic anemia. Parietal cells produce intrinsic factors and are essential for absorption of
vitamin BR12R. Pernicious anemia is a type of megaloblastic anemia resulting from
vitamin BR12R deficiency that develops as a result of lack of intrinsic factor in the stomach leading to
malabsorption of the vitamin BR12R. For the treatment of pernicious anemia use vitamin BR12R parenteral (IM or SC),
however do not use oral supplements.
Q. Vitamin BR12R malabsorption has been reported with amino salicylic acid, slow-release
potassium iodide, trifluoperazine, ethanol, metformin and oral contraceptives. Oral absorption
is decreased by anticonvulsants, colchicine, Q. metformin, neomycin and proton pump
inhibitor (omeprazole).
All persons over 50 and elderly should get vitamin BR12 Rsupplements of approximately 2 mcg daily.
QAlerts!
1) What vitamin is deficient in elderly? BR12
2) Important for maintenance myelin (its damage cause neurological signs)? Folic acid
3) What gastric secretion is required to be absorbing vitamin BR12R? Intrinsic factor
4) What vitamin that is deficient in vegan diet (NO dairy and No meat)? BR12
5. Long term use of metformin can cause deficiency of? Malabsorption of vitamin BR12
Folic Acid (Vitamin B 9)
· A conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA)
that forms pteroic acid.
· Animal cannot synthesize PABA or attach glutamate residues to pteroic acid, thus requiring folate
intake in the diet.
· Source: Yeast, leafy vegetables, and animal liver.
· Dietary requirements: An increase in the daily intake of folate during pregnancy is needed and doubled
by the third trimester of pregnancy.
· Q. Deficiency: Folic acid deficiency in pregnancy can cause neural tubule defect (NTD). Health
Canada recommends that all women capable of becoming pregnant take 0.4 mg of folic acid daily, in
addition to the amount of folate found in a healthy diet. It is assumed that women will continue taking a
supplement of 0.4 mg daily until pregnancy is confirmed and they enter prenatal care.
Q. Drugs that ¯ folic acid: Anticonvulsants (carbamazepine, phenytoin), oral contraceptives, methotrexate,
5- flurouracil, sulfonamides, trimethoprim, sulfasalazine and dapsone.
Folic acid
6B teridyl group analog 7PB ABA analog
Methotrexate Trimethoprim/sulphamethoxazole
Sulfonamide antibiotics
Folic acid supplements pregnancy
In pregnancy prophylaxis, folic acids 1 mg supplements should begin 3 months before conception
. In pregnancy recommended dietary folate (RDF) intake/day is 0.6 mg.
Q. Folic acid supplements in pregnancy 5 mg daily po x 10-12 wks with history of neural tubule (NTD)
defect reduce the risk of neural tubule defect and therapy with carbamazepine or valproic acid
Folinic acid (Leucovorin)
DHFR: Dihydrofolate reductase
Q. Methotrexate inhibits à Dihydrofolate reductase (DHFR) cause deficiency of folic
acid. Folic acid metabolized by DHFR. If methotrexate and folic acid combined. Folic acid cannot meta
bolize because methotrexate inhibit DHFR.
Q. Folinic acid (Leucovorin) is synthetic form of tetrahydrofolate. The folate form is available
in natural product. Leucovorin is used as rescue therapy in methotrexate toxicity.
Leucovorin is a reduced form of folic a26T cid2,6T which is readily
converted to other reduced folic a26T cid26Tderivatives (e.g., tetrahydrofolate).
QAlerts!
1) Folic acid supplements are used in pregnancy to prevent? NTD
2) OTC folic acid is? 0.6 mg to 1 mg
3) Deficiency of folic acid can cause? megaloblastic anemia.
4) Drugs that deficiency are folate antagonist such as ? sulfonamides, methotrexate, phenytoin
and carbamazepine.
5. Dose of folic acid in pregnant women using antiepileptic drugs? Folic acid 5 mg/day
6. Dose of folic acid in patient using methotrexate? Folic acid 5 mg/wk
7. Methotrexate overdose toxicity can be reversed by? Folinic acid (tetrahydrofolate)
Ascorbic acid (Vitamin C)
Ascorbic acid is derived from glucose via the uronic acid pathway. It is required for
maintenance of normal connective tissue “collagen” as well as wound healing.
Hydroxylation of proline residues in collagen is the most important reaction that requires ↓ VITAMIN C CAUSE (COMMON IN
as cofactor. SMOKERS)
Source: Citrus fruits, tomatoes, strawberries, broccoli etc. COLLAGEN DAMAGE SLOW WOUND
Deficiency: Q. Scurvy. Cause of vitamin C deficiency is poor diet and increased HEALING
requirements; especially during severe stress or trauma (vitamin C is readily DECREASE IRON ABSORPTION
absorbed).
Symptoms: Easily bruised skin, muscle fatigue, soft swollen gums, decreases wound
healing and hemorrhaging, osteoporosis, and anemia.
Q. Ascorbic acid is a good water-soluble antioxidant (oxidizing agent) and an acidifying agent used to treat overdose of
base drugs. Vitamin C is deficient in smokers, thereby vitamin C supplements.
QAlerts!
1) What vitamin is deficient in smokers? Smoking severely decreases vitamin C in blood.
2) What vitamin is an essential for the synthesis of “collagen” in connective tissues? Vitamin C
4. Example of water-soluble antioxidant? Ascorbic acid.
Vitamin A
Bcarotene consists of 2 molecules of retinal linked at their aldehyde ends, also referred as provita
min A. Very effective as antioxidant. With 3 active molecules. Q. Beta
carotene à retinol à retinal à retinoic acid. Beta carotene is a precursor of vitamin A. Rhodopsin is
active form of vitamin A, present in rods. Q. Rhodopsin is active form of vitamin A in vision (11-cis
retinal to 11-trans retinal). Thus Q. deficiency of vitamin A causes night blindness.
Q. Overdose or excessive dose of vitamin A can cause toxicity. Excessive accumulation of vitamin A in the
liver can lead to toxicity, which manifest as bone pain, hepatosplenomegaly, nausea
and diarrhea. Avoid high dosages in pregnancies because it is teratogenic. Avoid in renal disease.
Vitamin A ¯ Vitamin A
Night blindness Acute toxicity: nausea, vomiting, vertigo, blurred vision.
Xerophthalmia Chronic: alopecia, (DOSE >2900 U) hepatotoxicity, dry skin,
Immunosuppression hepatomegaly, arthralgia.
Bitot’s spot Q. Teratogenicity.
QAlerts!
Precursor of vitamin A is? Beta
carotenoids. Vitamin A overdose
can
cause? Toxicity Recommended vita
min A dose is? 2500 IU daily
Color blindness is associated with which photoreceptors? Cones
Lycopene, lutein, zeaxanthin is common in eye vitamin are? Vitamin A derivative or carotenoids. Zeaxanthin is
carotene analog is present in? macula in eye
Which vitamin can be toxic in pregnant women? Vitamin A
Retinoids
Topical Tretinoin is? Isomer of 13-Trans retinoic acid
(all Trans) Oral isotretinoin is? Isomer of 13-
Cis retinoic acid
Isotretinoin (Accutane) is 13-cis retinoic acid and this is oral only. The Tretinoin (Retin-A) is 13-
trans retinoic acid and this is topical (cream, gel and lotion) ("TTT").
Adapalene: Derivative of naphthoic acid with retinoid like
properties. Acitretin or etretinate is an aromatic retinoid.
Tazarotene; a topical retinoid used for psoriasis.
Vitamin D
There are three major types of vitamin D
Vitamin DR2R (ergocalciferol): from plant dietar
y sources. Vitamin DR3R (cholecalciferol): Active
vitamin D Calcitriol (most active form of vitamin DR3R)
Q. It is a steroid hormone. Q. Active form is 1, 25-dihydroxycholecalciferol (Vitamin DR3R) is derived
from ergo sterol and from 7-dehydrocholesterol (produced in the skin).
In the skin 7-dehydrocholesterol is converted to cholecalciferol following UV
irradiation. Ergocalciferol (DR2R) is formed by
UV irradiation or ergosterol. Chronic renal failure can cause deficiency of vitamin DR3R.
Source 1-liter milk fluid/day 400 IU vitamin DR3R. Q.Person with risk for osteoporosis and taking bisphosphonates
should take 800 to 1200 IU vitamin DR3R/day.
Dietary source: Dairy, found fish liver oil and eggs and also produced from skin.
Q. Deficiency: Rickets (weak bones and decaying teeth) in children and osteomalacia in adult. Symptoms:
Rickets is characterized by improper mineralization during development of the bones resulting in soft
bones. Osteomalacia is characterized by demineralization of previously formed bone leading to
increased softness and susceptibility to fracture.
Q. Vitamin D supplements 400-800 IU daily. Excessive intake >1000 IU can lead to hypercalcemia and
then cause nephrolithiasis and >75,000 IU associated with osteoporosis bone resorption.
Q. Newborn (infant) on breast-feeding should get vitamin D drops 400 units daily.
1-alpha hydroxylase
1,25-(OH)R2R DR3 Q. Vitamin D insufficiency is a common problem in Canada. The average Canadian does not
meet all vitamin D needs through diet, and Osteoporosis Canada recommends 800–2000 IU vitamin D per
day for individuals who are >50 years of age and at risk for osteoporosis.
QAlerts!
Vitamin D R is? steroidal hormone
Tocopherol (Vitamin E)
Act as a natural antioxidant by scavenging free radicals and molecular oxyge
n. Storage site of vitamin E is in adipose tissue (fatty tissues).
Tocopherol consists of 4 types of vitamin E, alpha, beta, gamma, and delta.
Q. Alpha tocopherol is the strongest antioxidant among all tocopherols. Deficiency occurs only with
fat malabsorption (ADEK).
Dietary requirements: Increased intake of vitamin E is recommended in premature infants fed formulas that ar
e low in vitamin as well as in persons consuming a diet high in poly saturated fatty acids.
Symptoms: Q. Increase in red blood cell fragility (decrease cell
integrity). Deficiency: peripheral neuropathy, retinopathy, skeletal
muscle atrophy.
VITAMIN E ↓
NEUROPATHY, RETINOPATHY, MUSCLE ATROPHY
Phyto quinones (Vitamin K)
Three types of vitamin K:
· Vitamin KR1R: Phylloquinones: Found in plants
· Q. Vitamin KR2R: Menaquinone-4: Made by bacteria or fermentation.
· Vitamin KR3R: Menaquinone-7: Synthetic and because of the generation of free radical it
is considered as toxic.
Vitamin KR1R (phylloquinone) is derived from green vegetables, KR1R used mainly
for blood clotting in liver.
Q. Vitamin KR2R (menaquinone)
is produced by intestinal bacteria. Non coagulation actions such as metabolism, bone mineralization, cell
growth, metabolism of blood vessel wall cells.
Vitamin KR3R is a synthetic menadione. When vitamin KR3R is administered. It will be alkylate
d to one of the vitamin KR2R forms of menaquinone.
Dietary requirements: It maintains normal levels of blood clotting protein factors 2, 7, 9, 10, and
Q. protein C, and protein S.
Deficiency: Hemorrhagic syndrome (for infants due to less bacterial in colon), bleeding, elevated prothrombin tim
e.
Vitamin K is given to newborns who do not have enough of it naturally occurring to prevent clotting problem
s.
Q. Vitamin K is antidote of warfarin.
Active vitamin K (reduced)
Coagulation mechanism in liver. Metabolism and bone
Act on clotting factors 2, 7, 9, 10 mineralization, cell growth
QAlerts!
1) What vitamins are synthesized by bacteria? Vitamin KR2R (Menaquinone)
2) What are Vit. K clotting factors! 2,7, 9, 10 (01972)
3) Vitamin K is essential for prothrombin in liver.
4) Vit. K sources? Dark green vegs and synthesis by intestinal bacteria.
5) Vitamin K? Facilitates normal blood coagulations.
6) Warfarin antidote is? Vit. K
7) Protein C and cofactor protein S? act as anticoagulant and prevent blood clot
8) Some new born babies get the vitamin K injections.
Vitamin B5/ Pentothenic acid
Diclectin: Pyridoxin+ doxylamine). With levodopa ↑ N&V
Vitamin B7/Biotin Raw eggs cause deficiency
parietal cells of mucosa.
↓by folate antagonist, methotrexate,
phenytoin, sulfa drugs.
Alpha tocopherol is the strongest antioxidant.
Questions Alerts!
Common questions in pharmacy exam is to ask!
Bacterial Structure: Endotoxin (pyrogen) of gram negative and exotoxins gives positive organism
Classification of microbes, bacteria, virus, fungi, protozoa.
Infective organism of common infections like pneumonia, traveler's diarrhea, toxic shock syndrome, endocarditis,
cellulites, meningitis, syphilis, athlete’s foot and warts.
Aerobic and Anaerobic bacteria
Q. Obligate aerobe, need oxygen: Generate H 2 O2 , act as bactericidal. Detoxification mechanism by Superoxide
dismutase. Enzyme to neutralize peroxide like hydrogen peroxide (H 2 O 2 ).
Q. Obligate anaerobe has no superoxide dismutase. No detoxification mechanism so bacterial death.
Q. Facultative anaerobe: Grow with or without oxygen. Most pathogenic bacteria can shift from fermentative to
respiratory metabolism.
Aerotolerant anaerobes: Similar to facultative, remains fermentative.
Capnophilic anaerobes: Require CO 2 example Bacteroide fragilis (gram –ve anaerobe).
QAlerts!
Example of cluster cone shapes bacteria? Staph
Atypical bacteria
Mycobacterium
Fungi
Cell membrane contain ergosterol layer.
Protozoa
Protozoa are unicellular or single cell organisms and classified based on flagellates.
**
Gram +ve Gram –ve
Stain blue or purple Stain red or rose pink
Techoic acid, peptidoglycan Lipopolysaccharide (LPS) in outer membrane
Peptidoglycan layer is thick Peptidoglycan layer is thin
Q. Exotoxin is a metabolic product. Q. Endotoxin is a metabolic product
Exotoxin is thermolabile (heat sensitive) destroyed at a Q. Endotoxin is more toxic than exotoxin, destroyed at higher temperatures.
temperature over 60 oC. Q. Pyrogen or toxins are removed by Q. Pyrogen or toxins are removed by double distillation.
double distillation.
Exotoxin is a high molecular weight protein. Endotoxin a complex structure made up of phospholipid, polysaccharides and
protein.
QAlerts!
Staph. aureus stains? blue
Exotoxins are metabolic product of? Strep or Staph
Pyrogen or toxins are removed by? double distillation.
GRAM +ve GRAM –ve
( aerobic bacteria) aerobic bacteria
Gram + ve cocci Gram –ve cocci
Streptococcus (in short Strep.) Catalase (- NISSERIA
ve) N. gonorrhea
S. pyogenes (Group A) N. meningitis
S. agalactiae (Group B) Moraxella catarrhalis
S. bovis (Group D)
S. pneumonia (alpha hemolytic)
Gram –ve bacilli (rods)
S. viridans (alpha hemolytic)
Staphylococcus (in short Staph.) Escherichia coli (E. coli)
S. aureus (Catalase +ve) Klebsiella pneumonia
S. saprophyticus Enterobacter spp.
S. epidermidis Shigella
Proteus mirabilis
Enterococcus Salmonella
S. typhi
Gram +ve bacilli S. enteritidis
Cyanobacteria diphtheriae Helicobacter pylori
Listeria monocytogenes Vibrio cholerae
Bacillus cereus Pseudomonas aeruginosa
Pasteurella multocida
H. influenza
H. duceryl
Legionella pneumophila
Yersinia
Y. enterococolitica
Y. pestis
GRAM +VE and anaerobic bacteria GRAM –VE and anaerobic bacteria
Clostridium Fusobacterium,
C. perfringens Bacteroides
C. tetani B. fragilis
C. difficile
C. botulinum
*The catalase test is used to identify organisms that produce the enzyme “catalase”. This enzyme detoxifies hydrogen peroxide
by breaking it down into water and oxygen. This test is used for differencing infections of Staph which produces catalase enzyme
and Streptococci which does NOT produce catalase enzyme.
Examples: Catalase +ve; Staph aureus.
QAlerts!
E. coli? Gram -ve bacilli
Infections causative organisms
GRAM +VE BACTERIA
Gram +ve Cocci Causative organism Antibiotics
Found on the skin and in the nose.
Boils, and Septicemia.
Staphylococcus aureus Food poisoning Penicillin G and Penicillin V, cefalexin, MRSA:
Catalase +ve Q. Wound infections, skin infections impetigo, vancomycin IV
and purulent cellulitis.
Q. Toxic shock syndrome (TSS) or septic shock.
Beta-hemolytic streptococci e.g. Strep Tonsillitis, Q Cellulites non Antistaphylococcal penicillin’s
Dicloxacillin (po), Nafcillin (inj), Oxacillin (Inj)
purulent, impetigo. Scarlet fever, Septicemia may Clarithromycin
pyogenes (Group A Strep: GAS) cause immune-mediated disease (e.g. rheumatic Erythromycin
fever). Azithromycin
Aminopenicillin
Amoxicillin, ampicillin (inj)
Q. Pneumonia (CAP), Otitis media, Meningitis, Amoxicillin/clavulanate (Augmentin)
Streptococcus pneumonia
Sinusitis, Pharyngitis Clarithromycin
Azithromycin
Doxycycline
Q. Endocarditis associated with
Alpha hemolytic
dental caries. However most common cause Amoxicillin, penicillin G, clindamycin
Streptococci viridans
dental caries is S. mutan.
Alpha-hemolytic Instrument contamination. Catheter infections,
S. epidermidis UTI.
Gram +ve bacilli
Erythromycin or penicillin's (to eliminate
Corynebacterium diphtheria Q Diphtheria (disease due to toxin production). carrier state) and
Tetracycline.
Clostridia sp.
Tetanus
Q Cl. tetani Q vancomycin oral, fidaxomicin or
Gas gangrene
Q Cl. perfringens Metronidazole po
Botulism
Cl. botulinum
Q. Pseudo membranous colitis
Q Cl. diffi cile
**
QAlerts!
A 65-year-old man who developed a harsh, productive cough, fever 4 days prior to being seen by his MD. He has been
prescribed amoxicillin 1 g tid for 3 days. What is the most common causative agent of community acquired pneumonia? Strep.
pneumonia.
What antibiotic is the most effective for S. pneumonia infections? amoxicillin
If patient medication profile shows patient had true beta lactam allergy and experienced anaphylactic reaction. What is the
treatment for outpatient community acquired pneumonia? Clarithromycin or azithromycin or doxycycline
5-year-old girl used amoxicillin for pneumonia in the past 2 months ago and now experiencing reoccurrence of CAP. What is
appropriate antibiotic? azithromycin
60-year-old diabetic patient diagnosed with mild purulent cellulitis. What is the most common pathogen associated? S. aureus
What is the first line antibiotic? Cephalexin 5 days.
Patient lab culture shows MRSA. What is the best empiric antibiotics? SMX/TMP or doxycycline
GRAM -VE COCCI
Gram -ve cocci Empiric treatment
Penicillin G
Meningococcal meningitis +/- shock commensal Ceftriaxone,
Neisseria meningitides
of upper respiratory tract. Cefuroxime Na
Rifampin
Acid-fast bacilli
Isoniazid
Q Active Tuberculosis (weight loss, coughing, fever, sweating Rifampicin
Mycobacterium
and chest pain). The most common cause of infectious death Streptomycin
tuberculosis
world-wide. Ethambutol
Pyrazinamide
Dapsone
Mycobacterium leprae Leprosy
Rifampicin
SPIROCHETE
Spirochetes
Q Syphilis (A STIs cause genital ulcers or chancres). A single Q Benzathine Penicillin G IM inj x 1 dose of 2.4
large ulcer and painless. million units.
Q Treponema pallidum
Penetrate through broken skin or mucus membrane usually Ceftriaxone 1 g daily IV/IM x 10 days.
through sexual contact. Doxycycline
* Genital herpes ulcers are often multiple, small and painful.
**Penicillin G benzathine not used as IV, it can cause respiratory arrest and death.
QAlerts!
MP a 30-year-old man diagnosed with sexually transmitted disease after he was found have genital ulcer. His medication
history shows in the past he had penicillin allergy for which he was hospitalized with hive, shortness of breath, anaphylactic
reaction. What spirochete is causative agent of syphilis? T. pallidum
What is treatment of syphilis? doxycycline
Dog bite infections
Most frequently isolated organisms Q. Pasteurella spp, streptococci, staphylococci, Moraxella, and Neisseria. Most common
anaerobe is Fusobacterium sp.
Treatment: Amoxicillin/clavulanic acid
Cat bite infection
Frequently caused Pasteurella multocida, Streptococci, Staphylococci, Moraxella.
Treatment: Amoxicillin/clavulanic acid
Human bite infection
Most common caused by normal oral flora, including both aerobic Strep and Staph and anaerobic
Bacterial infections caused by infected needle
Q, Common infections that result from IV drug use are Steph aureus .
FUNGI
Commonly 5 superficial or skin types of fungi;
Tinea Type of infection Site of infection Treatment
Tinea pedis Athlete’s foot Between toes Clotrimazole 1% cream x 6wks.
Tinea ungulum Onychomycosis or nail fungal Toes nail or finger nail Itraconazole, terbinafine oral
infection
Tinea capitis. Ringworm of scalp scalp Clotrimazole 1% cream
Tinea corporis Ringworm of the body body Clotrimazole 1% cream
Tinea cruris Jock itch; between thigh groin Clotrimazole 1% cream
Yeasts
Candida: Vaginal infections and oral thrush
Cryptococcus
Molds
Aspergillus
Zygomycetes
Fusarium
Dimorphics
Histoplasma
Blastomyces
Coccidioides
Paracoccidioides
Dandruff is caused by fungi Malassezia globose.
Seborrhea dermatitis (greasy hair) caused exacerbation of sebaceous gland and fungi Seborrhea capitis.
Fungi: Have thick, ergosterol containing cell walls and grow in humans as budding yeast cells and slender tubes (hyphae).
Q Clotrimazole 200 mg/vaginal tab, 1-tab daily PV x 3 days
Oral Thrush, mucocutaneous Miconazole
Q Candida albicans (yeast)
infection, vulvovaginitis Fluconazole 150 mg PO x 1 dose
Nystatin
Q Clotrimazole 1%, miconazole,
Tinea pedis Q Athlete’s foot
Tolnaftate (topical).
Usually itchy, circular rash, patches of hair loss or scaling on
Tinea corporis Q Ringworm fungal infection.
scalp.
Q Terbinafine 250 mg PO 12-24 wks (toe nail), 6-12 wks
(finger nail) and Itraconazole 150-300 mg once weekly PO.
TOE OR NAIL FUNGAL
Q ONYCHOMYCOSIS 12-16 wks (finger nail), 18-26 wks (toe nail).
INFECTIONS.
Eficonazole 10% solution (Jublia), apply 1 drop once daily
up to 48 wks.
Sporotrichosis or
Abscesses (puss)
granulomas
Allergic reactions,
Aspergillus sp. Ubiquitous airborne filamentous fungus.
opportunistic infections
Meningitis in
Cryptococcus neoformans Present in soil and pigeon droppings
immunocompromised
**
QAlerts!
29-year-old pregnant women presents at your pharmacy and she experiencing vaginal itch and curdy discharge. After differential
diagnosis. Pharmacist determine that as vaginal candidiasis. What is appropriate action? Refer to MD
PROTOZOA
Protozoa
Chloroquine, hydroxychloroquine Q Mefloquine,
Malaria; Four species infect man via
Q Plasmodia sp. atovaquone/proguanil.
biting female Q anopheles’ mosquito.
Primaquine, Doxycycline
Low grade gastrointestinal disease:
Giardia lamblia Metronidazole
giardiasis.
Amoebic dysentery (are infective
Entamoeba histolytica Metronidazole
when swallowed, traveler’s diarrhea).
and Giardia lamblia (intestinal Ciprofloxacin
Severe, may invade and spread to the
protozoa) Cotrimoxazole
liver.
Q Metronidazole po (oral) 2 g single dose or 500
Q Trichomonas Vaginal infections
mg bid f7d
Trichomonas characteristic yellow frothy vaginal discharge
Mnemonic: GET Metro
DNA VIRUS
DNA viruses
Adenoviruses Conjunctivitis, Sore throat
Enveloped: DS
HSV 1 and HSV 2 can cause oral and genital lesions.
Q. Herpes viruses: Acyclovir
HSV 1 causes cold sores and keratoconjunctivitis.
Herpes simplex virus I & II Valacyclovir (prodrug of acyclovir)
VZV can cause (Varicella: chickenpox, zoster: Shingles),
Varicella zoster Famciclovir
glandular fever,
Q. Cytomegalovirus (CMV)
Roseola infantum (sixth disease).
Epstein-Bar (EB virus)
Hepatitis B Transmitted via blood and body fluids and
Q. Hepadnavirus: Hepatitis B Interferon alpha
sexual contact.
Slapped cheek disease (fifth disease, and erythema
Parvovirus: parvovirus B Can cause aplastic crises
infectious).
HPV vaccine. Implicated in cancer of the
Papovaviruses: Human papillomavirus cervix.
Q Warts, cervical cancer,
(HPV) Q Vaccine Gardasil. Quadrivalent human
Hemorrhagic cystitis.
Polyomavirus papillomavirus (types 6, 11, 16, 18)
recombinant vaccine.
Poxviruses Molluscum contagiosum, smallpox
RNA VIRUS
RNA viruses
Q Neuraminidase inhibitors. Oseltamivir (A and
B): treatment 75 mg bid f5d; prevention 75 mg
Orthomyxoviruses:
daily f10d
Q. Influenza A and B
Zanamivir (A and B): Boxed warning:
Influenza A Influenza (flu)
bronchospasm, decline respiratory function.
subtype H1N1 (hemagglutinin, neuraminidase)
Amantadine, Ribavirin, Rimantadine (influenza
A).
Yellow fever, chronic hepatitis.
Flaviviruses: Yellow fever, Hepatitis C
Paramyxoviruses: Parainfluenza, RSV, Measles Q Respiratory infections: Croup
May be severe in infants
Mumps Q Measles, mumps
Picornaviruses: Enteroviruses (e.g. poliovirus), Meningitis, common cold (rhinoviruses).
Rhino has runny nose
rhinoviruses, Hepatitis A Hepatitis
Reoviruses: rotavirus Gastroenteritis cause stomach flu.
Retroviruses: HIV-1, 2 AIDS, T-cell leukemia, NRTI, NNRTI
HTLV I, II Spastic paraparesis Protease inhibitors
Q. Rhabdoviruses: rabies Rabies Zoonotic infection (animal bites)
Toga viruses: Rubella, Q German measles (Rubella),
Alpha viruses Encephalitis
Coronaviridae family: Covid-19 is new means not resembling to
SARS Co V, formerly known corona viruses.
MERS Co V; Spike protein of SARS-CoV-2 is different
SARS Co V-2 (Covid-19). than previous SARS-CoV.
QAlerts!
Rubella is? German measles
Find answers for the tips from the following table:
1. S. pneumonia 2. Chlamydia trachomatis 3. Pseudomonas aeruginosa
Questions Alerts!
Common questions in pharmacy exam is to ask!
This chapter reviews basics of chromosomes, gene, nucleic acids, DNA structure and functions, replication, Mutations and
recombination. RNA structure and functions, transcription from DNA and translation to synthesize proteins. Also review topics
such as recent development of gene cloning and genetic engineering.
Prokaryotic Eukaryotic
Primitive nucleus (no nuclear membrane) QLarge single DNA Have nucleus DNA is linear, and DNA bound to proteins Animal: no cell wall
molecule (circular) is also known as plasmid. Contain cell wall but cell membrane No chloroplast Plantà cell wall and chloroplast. Cell
(rigid): covalently bonded short chains of amino acids. Cell membrane is present. Mitochondria present
wall contain murein (polysaccharide chain) Chloroplast absent
Mitochondria absent
Prokaryotes Present in bacteria Present in animal, plant, fungi, parasites, algae, and protozoa.
Bacteria are reproduced by type of cell division called binary Mitosis and meiosis
fission.
Q. Single chromosomes (haploid). DNA is not separated from Q. Paired chromosomes (diploid or more).
cytoplasm
70 S ribosomes 80 S ribosomes
**
QAlerts!
It is a series of membranes extending throughout the cytoplasm of eukaryotic cells. Cytochrome P450 present in
endoplasmic reticulum.
Q. Rough endoplasmic reticulum helps in protein synthesis.
Q. Smooth endoplasmic reticulum helps in lipid synthesis, this does not contain ribosome.
Q.Lysosomes
Drop like sac of enzymes in the cytoplasm. Help digest food or nutrient within cells.
Mitochondria
Mitochondria aka as power house of the cell. Aerobic glycolysis releases energy in the form of ATP.
Centrosomes
Q. Microtubule organizing center and contains two centrioles in the animal cell. The centrioles act as anchor that microtubules
attach to during cell division to move chromosomes. Microtubule does cell division or formation spindle apparatus during cell
division. Regulates the cell division cycle.
Peroxisomes
Q. Metabolise waste. Contains enzymes that break down fatty acids and carbohydrates and decomposes hydrogen peroxides.
Series of flattened sacs. Synthesize the cell’s proteins and lipids. Process and transports proteins and other material out of cell.
Vacuoles: They are big, fluid like structures, and may occupy more than 75% of the plant cells.
Cell Division
There are two types of cell division mitosis and meiosis in eukaryote cells. Binary fission DNA replication occurs in prokaryotes
leads to chromosome segregation.
MITOSIS MEIOSIS
Occurs in dividing somatic In sperms and egg cells
cells, fertilization afterwards.
All times Post puberty in males.
QAlerts!
Q. Chromatin: The chromatin is a complex of macromolecules found in cells, consisting of DNA, protein, and RNA. The primary
function of chromatin is 1 to package DNA into a more compact, denser shape. 2. To reinforce the DNA molecule to allow
mitosis. 3. To prevent DNA damage and 4. Control gene expression and DNA replication. The primary protein component of
chromatin is histones. Chromatins are found only eukaryotes.
Q. Nucleosomes: A nucleosome is the basic unit of DNA packaging. It consists of a segment of DNA wound around a core
(octomer) of 8 histone proteins.
Q. Histones are proteins around which DNA winds for compaction and gene regulation. Histones are highly alkaline proteins
found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief
protein components of chromatin, acting as spools around which DNA winds, and playing a role in gene regulation.
Gene
Q.A gene is a series of codons that specifies and express a particular protein formation.
The function of gene is providing exact information for the synthesis of the specific amino acid sequence of proteins synthesis.
QAlerts!
Genome
The genome of an organism is its complete set of gene or genetic material present in cell organism. All the genetic information
in an organism is referred collectively as a “genome ”proteins.
Genotypes
Phenotype
Homozygous Heterozygous
Homozygous genotype for particular gene inherits two Presence of two different alleles at a specific gene position.
of the same alleles.
Commonly this interaction is based on dominance. The alleles
It means biological parents contributes to the same that expressed more strongly are called “dominant” and the
variants. other is called “recessive”, so recessive may not be expressed
at all.
Ultra-rapid metabolizer carries 2 amplified alleles. Extensive metabolizer carry one wild allele and one amplified
allele.
QAlerts!
If a woman is homozygote of dominant and the man is heterozygote of dominant the percentage of being homozygote
dominant is:
A. 25% B. 50% C. 75%
Tips: AA AA Aa Aa
A. Homozygous recessive
B. Homozygous dominant
C. Heterozygous dominant
D. Heterozygous recessive
Ans. B
A man has two alleles for Huntington disease and women is normal. What is chance of their will have the Huntington disease?
A. 100%
B. 50%
C. 25%
D. 0%
A gene is a DNA sequence that encodes a protein or an RNA molecule. Each chromosome contains many genes, i.e. the basic
physical and functional units of heredity. Each gene exists in the particular position of particular chromosome. In human
genome, it is expected that there are 30,000 to 35,000 genes. In prokaryotic genome, one gene is corresponding to one protein.
Whereas, in eukaryotic genome, one gene can correspond to more than one protein because of the process called as “ alternative
splicing”.
Nucleotide structure
Nucleotides are the building blocks of all nucleic acid molecules. Nucleotide consist of 3 units that are base, sugar and phosphate
and nucleoside consist of sugar and base.
There are two chemically different nucleic acids deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA).
Nucleic acid (DNA and RNA): structural units consist of three essential components, i.e.
Q. The DNA is composed of two strands of nucleotides held together by hydrogen bonds. These strands each run from 5’ to 3’ or
opposite direction one to another.
Forms of Nucleotides
Thymine (T)
**
DNA RNA
Adenine (A) Adenine (A)
Cytosine (C)
Cytosine (C)
Guanine (G)
Guanine (G)
Uracil (U)
Thymine (T)
Single stranded
Double stranded
2’Ribose (-OH)
2’-Deoxyribose (-H)
DNA Complementary pair RNA complementary pair
A= T A= U
G=C G=C
Q. Pairs of purines with pyrimidines formed by hydrogen bonds. When strands base pair, they are said to be complementary.
QAlerts!
If complimentary pair incorrectly compliments other than A to T and G to C can result into mutations. Indel is insertion or
deletion mutations.
There are 3 possible mutations like purine to purine, pyrimidine to pyrimidine and purine to pyrimidine.
Point mutation: sickle cell disease, Q. cystic fibrosis, B-thalassemia, Q. Factor V Leiden (a mutation of one of the clotting factors
in the blood that increase risk of blood clot).
QAlerts!
Single gene mutation or monogenic disease is caused by single gene mutation are? Cystic fibrosis or Huntington’s chorea.
Codon
The codon is present in the messenger RNA (mRNA), they are Adenine (A), Guanine (G), Cytosine (C), Uracil (U). These four
nucleotide bases produce three base codons. There are 64 different combinations of these bases. Sixty one of 64 codons
normally produce 20 common amino acids. However, there are 3 codons UAG, UGA and UAA, do not produce amino acids they
are known as stop, nonsense or termination codons. When one of the codons appears the synthesis of peptide chain is stopped.
TRANSCRIPTION TRANSLATION
DNA --à mRNA mRNA à tRNA.
Nucleus Cytoplasm and ribosome
What step comes first in protein synthesis? Transcription Anticodon is present on? tRNA
Making mRNA from DNA is called? Transcription Making DNA from mRNA is? Reverse Transcription (retrovirus).
Q. Antisense therapeutic agents target mRNA Codon-anticodon relation takes place in translation.
RNA polymerase transcribes DNA to mRNA.
Q.The site on DNA from which the first RNA nucleotide is transcribed is
called +1 site or the initiation site. The nucleotides that come before
initiation site are negative number are called upstream. The nucleotide
comes after the initiation site are downstream.
QAlerts!
Transcription
This is first step in cell protein synthesis, during this process information from DNA copied to mRNA. Q. The RNA polymerase
is the main transcription enzyme.
Q. Initiation
Q. The RNA polymerase binds to the DNA of the gene at a specific region called promotor.
Q. Downstream: DNA located in the direction in which RNA polymerase will transcribe.
Upstream: DNA located in the opposite direction in which RNA polymerase will transcribe.
Coding 5’-G-T-C-A-G-A-3’
Transcription termination
Polymerase transcribes a sequence of DNA as terminator signal and this process ends the transcription .
Translation :This is second step in cell protein synthesis. The protein synthesis occurs in ribosomes. During translation
information from mRNA is brought to ribosomes by tRNA. Q. This will determine the sequence of amino acids and protein
synthesis.
QAlerts!
The RNA polymerase binds to the DNA of the gene at a specific region called? promotor.
In transcription from which side the codon of DNA to mRNA attaches first and coding moves toward? downstream
Q. Reverse transcription
This begins when the viral particles (retrovirus) enters the cytoplasm of target cell. Q. Reverse transcriptase is an enzyme used
to generate complementary DNA (cDNA) from an RNA template. It is mainly associated with retrovirus. Example: HIV and non-
retrovirus, hepatitis B.
mRNA à DNA
DNA synthesized from a messenger RNA rather than from a DNA template. This type of DNA is used for cloning or as a DNA
probes for locating specific genes in DNA hybridization studies.
mRNA à cDNA
Exposure by UV lights, radioactive, radical oxygen, chemical compounds, viruses because DNA damage thus induce cancer and
various disorders.
Damage DNA is repaired by nonhomologous end joining and homologous recombination and various mechanisms.Drug
combination inhibits DNA repair in cancer cells;
First FDA approved drugs Olaparib as DNA damage repair enzyme PARP for killing cancer cells with defects in DNA repair due
to mutations in repair genes BRCA1and BRCA2.
Drugs inhibit DNA damage repair are olaparib in combination with VEGF inhibitor Avastin beneficial for ovarian
cancer.Vascular endothelial growth factor (VEGF) receptors that stimulates that formation of blood vessels. The medications
like Imatinib helps to stop cancer cells from repairing damage to their DNA.
DNA recombination
Plasmid
Q. Plasmid is extra chromosomal substance of DNA in prokaryotes. Plasmids are often used for DNA recombination and cloning.
Plasmids naturally exist in bacterial cells and some eukaryotes. Often the genes carried in plasmid provide bacteria with genetic
advantages such as antibiotic resistance.
MOLECULE A MOLECULE B
Refers to creation of similar populations of Refer to the modification of DNA in order to produce new types
genetically identical individual of organisms by inserting or deleting genes.
Occurs naturally or through molecular cloning An artificial technique
Cloning
Given a piece of DNA X, the process of duplicating it into many pieces is called.
The basic steps involve in cloning:
1) Q. Insert X into a plasmid vector with antibiotic-resistance gene and a recombinant DNA molecule is formed. Plasmids and
DNA fragments must have compatible RE ends for ligation by T4 DNA ligase. A linear product of DNA and the linearized
plasmid is firstly formed, followed by the joining of the opposite ends to form a circular product.
rDNA or recombinant DNA molecules formed by lab methods of genetic recombination (molecular cloning).
2) Insert the recombinant into the host cell (usually, E. coli). This makes use of a chemical based transformed method, where the
bacterial cells are made “competent” to take up foreign DNA by treating with calcium ions. After the recombinant DNA
molecules are mixed with the bacteria cells, a brief heat shock is applied to facilitate uptake of DNA.
3) Grow the host cells in the presence of antibiotic. Note that only cells with antibiotic resistance gene can grow. Note that when
we duplicate the host cell, X is also duplicated. (antibiotic resistance gene act as selectable marker to select the bacteria that
have up the plasmid (transformed), because when the mixture is agar plated with antibiotic in the medium, only those that are
transformed and have resistance gene survive and those without killed off.)
4) Select those cells contain both the antibiotic-resistance genes and the foreign DNA X. Some cells only contain plasmid vector
but without the foreign DNA due to unsuccessful ligation in step 1. The cells with foreign DNA X can be correctly selected by the
complementation of beta-galactosidase, in which the correct colony will show blue color.
QAlerts!
Plasmid function? Plasmids are often used for DNA recombination and cloning.
Endonucleases are? Enzymes that cleave the phosphodiesterase bond within polynucleotide chain a.k.a restriction
endonuclease.
Genetic Diseases
Cystic fibrosis
It autosomal recessive inheritance comes from both parents are carriers the CF gene.
CF cause inflammatory destruction of lungs which produce thick mucus.
CF cause chronic lung infections.
Diagnostic test includes sweat chloride tests, CFTR gene test
Treated by dornase alpha
QAlerts!
What enzymes are used for the treatment of cystic fibrosis? Pancreatic enzyme
Hemophilia
Hemophilia is a genetic disease often associated with X chromosome only. Thus, men can hemophilic or no
hemophilic; however, there is no carrier in men.
Hemophilia causes slow blood clot formation.
There are two types of hemophilia, that is type A and B.
Q. Hemophilia type A is due to deficiency of clotti ng factor 8 (antihemophilic factor).
Hemophilia type B is due to deficiency of clotting factor 9 (Christmas factor).
Gene therapy cures genetic diseases such as cystic fibrosis, sickle cell anemia, and hemophilia, in which defected genes are
identified and altered or by altering gene expression to prevent or cure genetic diseases and cancers, ADA deficiency
(adenosine deaminase deficiency), this cause autosomal recessive metabolic disorder that cause immunodeficiency.
Blocking
Cell containing faulty gene -----------à New gene product inactive faulty gene
1. Replacing a disease-causing gene with a new, functioning copy of the gene.
3. Introducing a new or modified gene into the body to help treat a disease.
QAlert!
For long term effective gene therapy, gene needs to be? fully integrated into chromosome
Antisense Technology
Antisense RNA
ATCG- 5’---5’-UAGC
DNA-----------------à mRNA ----------------à tRNA
Antisense drug
(oligonucleotides)
QAlerts!
Knockout mice
Transgenic mice
Genetically modified mouse that has its genome altered through the use of genetic engineering .
Apoptosis
In normal component of cell regulation, the suppressor gene Q. (tumor suppressor gene), arrest replication of a cell with
damaged DNA until the DNA is repaired. Failure to repair DNA and resume normal function will result in programmed cell
death, is referred as apoptosis. Q. In Gene therapy tumor suppressor genes are inserted into tumor lines to stimulate
apoptosis killing the tumor cells.
Genetic Testing
Disease that are associated with genetics, or mutations can be diagnosed treated with selective gene testing methods.
Pharmacogenetics or pharmacogenomics
Q. Pharmacogenetics is study of inherited genetic differences in drug metabolic pathways which can affect individual
responses to drugs.
Pharmacogenetics search for genetic variations that lead to individual differences in drug response. E.g. examining the
influence of carvedilol, a beta blocker gene on blood pressure.
Terminology
Genetic variations
A genetic variation occurs as either rare defects or polymorphism. Polymorphism are defined as variations that occur at a
frequency of at least 1% in the human population. Example the gene encoding cytochrome CYP450 enzymes CYP2A6, 2C9,
2C19, 2D6 and 3A4 are polymorphic.
To perform pharmacogenetics, the first step is detailed analysis of patient list of single nucleotide polymorphism.
Genes encoding variation or gene involved in pharmaceutically relevant biological activity affecting the drug response mainly
found in;
Most common drug metabolizing enzyme CYP450. Q. CYP3A4 (44%), CYP2D6 (25%), CYP2C9 (10%), CYP2C19 (5%).
CYP2D6 has the largest number of variations of all the cytochrome enzyme, and as much as 25% of all the medication
metabolized by 2D6.
Fast metabolizers
The presence of a single “17 variant gene causes a slight increase in CYP2C19 enzyme activity and CYP2D6 presence of “2
variant gene result in increase in CYP2D6 activity.
CYP2D6
Codeine ----------------------à Morphine
Guidelines recommend tricyclic antidepressant substrate of CYP2D6 is avoided in ultra-rapid metabolizers due to lack efficacy
compared to normal metabolizers.
Slow metabolizers
No enzyme activity or metabolizes certain medications at a significantly lower rate than normal .
Normal metabolizers
Trastuzumab is used to treat breast cancers type human epidermal growth factor receptor (HER2).
Overexpression of HER2 results in breast cancer which can diagnosed by below positive tests results.
Genotype tests are done to prescribe Trastuzumab (Herceptin). FDA has approved 2 tests for HER2 status;
Pharmacogenomics of warfarin
Warfarin metabolism is affected by CYP2C9 and VKORC1 (Vitamin K epoxide reductase complex subunit 1).
Variability in warfarin dosing among Caucasians and Asians can be explained by VKORC1
QAlerts!
VKORC1 is the warfarin target gene and is important to post translational carboxylation of vitamin K dependant clotting factor.
Pharmacogenomic of SSRI
Various CYP450 genotype platforms exist that have been approved for CYP2D6 and CYP2C19 by the FDA and can be used to
screen patient groups.
Pharmacogenomics of Carbamazepine
Populations with gene/allele genomic tests positive Human leukocyte antigen (HLA) typing or 1 or 2 copies of relevant allele.
HLA-B*1502: Frequent in East Asians: Han Chinese1-6%, North Asian; Japan 0.1%, Koreans 0.2-0.4%; Caucasians, Europeans,
Hispanics 0%
HLA*3101: Frequency North European 2-5%, Han Chinese 2-3%, Japanese 7-12%
HLA*1511: Frequency Singaporeans 2%, Koreans 3-4%, Caucasians, and African Americans 0%
Populations with gene/allele HLA-B*1502 increased risk of carbamazepine induced life-threatening hypersensitive reactions
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN).
Gene/Allele HLA-A*3101 and HLA-B*1511 increased risk of carbamazepine induced mild or severe cutaneous hypersensitivity.
Drugs with fatal hypersensitive reactions
Abacavir: HLA-B*5701 allele
Pharmacogenetic of statins
One of the most extensively studied gene is SLCO1B1, which encodes the OATP1B1 drug transporter responsible for statin uptake
into the liver. Patients who carry gene variant in SLCO1B1 gene produce a transporter with reduced function. This increases the
circulating plasma concentration of statin which is associated with increased risk of myopathy. The association is strongest with
simvastatin so thereby guidelines suggest simvastatin drug/dose changes to minimize risk of myopathy.
QAlerts!
How many types of nucleic acid? There are two chemically different nucleic acids: Deoxyribonucleic acid and
ribonucleic acid).
Building blocks of all nucleic acid molecules are the (nucleotides)
Purine bases (Adenine and guanine)
Pyrimidine bases (Cytosine, uracil and thiamine)
Base found only in RNA (Uracil)
All the genetic information in an organism is referred collectively as...(Genome)
DNA sequence that encodes a protein or an RNA molecule is a (Gene)
This is the first step in cell protein synthesis (Transcription)
A segment of gene situated between exons is a (Introns)
Split the DNA on specific site (lyase)
Join the DNA on specific site (ligase)
Small circular, extra chromosomal DNA molecule called....(plasmid)
What genetic disease often associated with X chromosome only?(Hemophilia).
Genome (DNA library), complete genetic information of one species.
What is plasmid? Small circular extra chromosomal carrying same genetic information.
What are centrosomes? A centrosome is made up of two centriole rings. Centrioles alter microtubule stability in cell
division and stop cell division.
Lysosomes are a sack like cellular organelle? that contains various hydrolytic enzymes thus breakdown waste.
Histones are?
Nucleosomes?
Transcription upstream?
Transcription downstream?
EVALUATING EXAM CHAPTER 16
Immunology
Questions Alerts!
Immunity
Non-specific Specific/adaptive
Q. Innate immunity: Natural and present at birth. Immediate (non-specific) response, in which inflammation is triggered by
direct damage to host cells. No memory cells. Does not remember foreign pathogens and does not provide ongoing
protection. Involves epithelial surface: Bactericidal activity by sweat (salt), subcutaneous secretions, and long chain fatty
acids.Skin, pH, mucus lining, saliva, body temperature interferon’s, cellular, gastric acid; gut microflora, respiratory tract,
cough/swallow reflex, cilia in respiratory tract.
Adaptive immunity is divided as Humoral immunity by B-Cells and cell mediated immunity by T-Cells
Lifelong immunity. Specific to antigen (bacteria, virus etc). NOT inherited. is acquired immunity. Not at birth. It takes times to
develop after first exposure antigens. Delayed (gradual). Has memory cells.
DIAGNOSIS
Neutrophils 55% to 75% Bacterial infection
Lymphocytes 20% to 40% Viral infection
Monocytes 0% to 7% Tuberculosis
Eosinophils 0% to 5% Parasites infection, Q Allergies Asthma
Basophils 0% to 1% Inflammation
QAlert!
Allergens binds with IgE and then IgE binds with mast cells that produce? Histamines
Lymphocytes
Lymphocytes are presents in lymphatic fluids and lymph nodes that includes B-cells and T-cells.
BCELL
Virgin B cells formed in bone marrow and release released in blood circulation, and initially they do not respond to an antigen. B
lymphocytes mature into plasma cell that secretes antibodies (immunoglobulins). Each type of B cell makes one specific antibody
which recognizes one specific antigen. B CELLS have thousands of receptors as identical antibodies in their membranes that allow
them to bind chemically to a small group of chemically related antigen.
Clonal Theory
Q.The Antigen selects which lymphocyte will undergo clonal expansion and produce lymphocytes with same type of antigen
receptors. Some become memory cells (long term immunity for same infection), B-cells become plasma cells and fight infection.
Structure of immunoglobulin's
The basic immunoglobulin structure is 4-polypeptide chain molecule containing 2 identical heavy chain and 2 light chains. The heavy
and light chain is bound together by disulfide bond. The molecule has two antigen binding sites and has valence 2. The molecule is
symmetrical.
QAlert!
Antibody structure consist of ? heavy chain, light chain linked by disulphide bonds.
What immune cells are associated with memory specific response? B-cells
Ig D Less than 1%, accounts for less than 1%. Binds B- cell receptors.
Ig E 1% located on the cell surface of blood, basophils and on connective tissue mast cells to trigger the secretion of inflammatory mediators
from these cells in the presence of specific antigen. IgE mediates allergic reactions (asthma). Q. Eosinophils (allergic) and basophils
have IgE antibodies receptor.
Q. Inflammation is related to basophils and allergies are related eosinophils. Ig E levels increased in allergic reactions.
Serum half is 2 to 3 days. When IgE bound to mast cells, the serum half-life could be several months. Antibody of allergy and anti-parasitic
activity.
Ig G Q. Predominant 70-80%, most common (abundant) of all Ig’s found in all body fluids (BLOOD, CSF, LYMPH). This is secreted at the end of
primary immune response and during memory responses. IgG1 to IgG4 and can cross placenta.
IgM 6% IgM is Q. the most potent activator of all immunoglobulins.
IgM1 to IgM2. First or primary immunoglobulin produced in body. It does not leave the blood in significant amount because of it
PENTAMERIC STRUCTURE (molecular size 900,000 Daltons). This accounts for ~ 20%. Serum half-life 9 to 11 days.
QAlerts!
T CELLS
Q, T-cells are produced from bone and mature in thymus. The most T cells can be classified by the presence of membrane
glycoproteins. Cluster of Differentiation (CD) or Cellular Differentiation marker is surface molecules found during the
development of Tcells in thymus. CD4 count is surrogate marker of disease control and progression, as well as patients’ risk of
opportunistic infection in HIV.
Helper T-cell (TH cells) CD4 cells Binds to MHC class II on dendritic cells and B-cells.
Q. Normal CD4 count is from 500 to 1500 cells per cubic millimeter of blood.
Cytotoxic cell CD8 Cells Binds with MHC class I
TC Cells Release toxin which initiates programmed cell death or Apoptosis via cytotoxic or
FAS ligand. Which FAS molecule present on infected cell.
Natural killer cells (NK- Which replicate very fast based on previous memory.
cells)
QAlerts!
T cell has two membrane proteins (alpha and beta or gamma or delta). These proteins define specificity of each T cell and several
other membrane proteins known as CD 3 complex occurs in cell mediate immune response.
The ability of immune system to recognize its own cells and distinguish these cells from foreign pathogens depends on a group of
protein markers found cell membranes called the major histocompatibility complex. These markers are present on the surface of
every cell and in human are called the human leukocyte antigens.
Q. Cytokines (Lymphokines)
Soluble protein molecules released by immune cells to communicate with other cells which act as intercellular mediators.
Cytokines bind to specific receptors on the surface of other cells.
Therapeutic cytokines: Types of cytokines (Lymphokines) includes Interferons, Interleukins , Colony stimulating factors (CSF),
Tumor necrosis factors and chemokines.
Interferons The interferons are the family of cytokines proteins, important in the immune response. Interferon proteins that are
secreted by cells when they become infected with virus. Q.Bind to nearby infected cells and prevent viral infection. This
increased resistance of cells to viral infection and slows the spread of disease.
There are three major types of interferon: Interferon’s inhibit viral infections and may have anticancer properties. Interferons
are indicated in hepatitis infections.
Interleukins : Interleukin regulates the Q. growth, activation Tcells and development of white blood cells. The interleukins
also called lymphokines. Twelve interleukins (IL-1 through IL-12) have been identified to date.
Colony Stimulating Factors : Colony-stimulating factors (CSFs) also called hematopoietic growth factors . Usually do not
directly affect tumor cells rather, they encourage bone marrow stem cells to divide and develop into white blood
cells, platelets , and red blood cells .
The CSFs stimulation of the immune system may benefit patients undergoing cancer treatment. Some examples of CSFs and
their use in cancer therapy erythropoietin, epoetin alpha, and epoetin beta. Darbepoetin (chemotherapy induced anemia
occurs within weeks to months). Therapeutic use: Q. Treatment of anemia resulting from chronic renal failure. Side effects:
Increase BP, thus monitor blood pressure.
Q.Granulocyte Colony Stimulating Factors: Produced by recombinant DNA technology. Q. Filgrastim (Pegfilgrastim) and
Sargramostim.
Tumor necrosis factors (TNFs):TNFs are produced by mast cells, macrophages and T-cells. They regulate immune responses
and inflammation. Many times, responsible for apoptosis.
QAlerts!
IL-11 is? Oprelvekin
Granulocyte colony stimulating factor (G-CSF) regulates? the production of neutrophils in bone marrow.
Filgrastim is used to treat? Chemotherapy induced neutropenia.
Excess, inappropriate and prolonged immune responses that cause damage to normal tissue.
Q. Anaphylactic reactions (shortness of breath, angioedema, GI allergies, dairy products, shellfish, and peanut.
hypotension).
Skin allergies, topical drugs (procaine).
Intravenous allergiesàinsect venoms.
Q.Atopic dermatitis (ECZEMA), pruritic (itching), allergic rhinitis,
asthma, and food allergies, conjunctivitis and urticaria
is treated
Type II (5- Cytotoxic/anti-body mediated hypersensitivity: Hemolytic anemia and thrombocytopenia are more common.
12 hrs)
Q.Hyperacute graft rejection
IgG and IgM binds to cell surfaces of antigen à Cell damage Q.BLOOD GROUP Transfusion mismatches.
(cytotoxicity)à can recognize self antigen.
Q.Rh disease (-mom & +baby), specific autoimmune diseases.
Q. Hashimoto thyroiditis, and myasthenia gravis, grave disease.
.
Type III Antigen-antibody (IgG/IgM) complex inflammation. More serious: Glomerulonephritis, vasculitis and lupus, arthralgia and
(3-8 hrs) rheumatoid arthritis.
Non-specific autoimmune disorders such as Q. systemic lupus
erythematous, Q. rheumatoid arthritis. Hepatitis infections, local
Immune complexes deposit into blood vessel
respiratory form of fungal reactions. Serum sickness.
walls à complement cascades and neutrophil
degranulation à Inflammation à damage tissue in lupus.
Q. Penicillin and sulfonamides. Q. Lymphadenopathy, fever, and rash-
first symptoms.
Q. Lupus: Abs bind to self DNA and self-protein.
Type IV Delayed type reactions mediated by cell T cells like TH1, TH2, Symptoms of type IV:
(24-48 CTL.
hrs)
Q. Contact dermatitis, micro vesicle formation, and spongiosis.
Q. Tuberculin (Monteux test) reaction gives erythema.
Q. Poison ivy.
Mnemonics:
Hypersensitive reaction is "ACID" Type 1 - Allergic (<30 min); Type 2 - Cytotoxic (5-12 hrs); Type 3 - Immune complex deposition
(3-8 hrs) and Type 4 - Delayed (24-48 hrs).
QAlerts!
Haptens
Q. Hapten is a low molecular weight or small molecules compounds that act as immunogens after chemically complexing to a
larger molecule or cell surface. Means Haptens complex with large molecules such as albumin, heparin, insulin and molecules
possessing multiple valences. After complexing with large molecule such as proteins albumin they elicit IgE production thereby
can cause hypersensitive reaction.
Opportunistic infections
Opportunistic infections are the infections that occurs often in weak immune system patients.
In HIV patients as disease progresses and develops in AIDs, and risk of opportunistic infections increases. Using prophylaxis
therapies will increase HIV survival rate.
cells /microL
350 M. tuberculosis Isoniazid + pyridoxine or rifampin
275 Kaposis sarcoma
200 Non-Hodgkins lymphoma
<200 P. carinii pneumonia (PCP) or P. jerovicii SMX/TMP
pneumonia(PJP)
2.A HIV patient with CD4 count 350, and PPD 5 mm is given tubeculosis prophylaxis of? Isoniazid + pyridoxine or rifampin
Autoimmune Disease : When the immune system mistakes self-tissues for non-self and mounts an inappropriate attack, the
result is an autoimmune disease. There are many different autoimmune diseases and can categorize in two major types organ
specific and non-organ specific.
Rheumatic fever
Antithyroid autoimmunity’s
Myxedema (hypo)
Hashimoto thyroiditis (hypothyroidism)
Graves disease (hyperthyroidism)
Myasthenia gravis (weakening of muscles)
Autoimmune pernicious anemia
Goodpasture’s syndrome
Autoimmune hemolytic anemia, thrombocytopenia, neutropenia, lymphopenia
Insulin dependent diabetes mellitus (IDDM)-type1
Multiple sclerosis
Non-organ specific autoimmune disorder. Sjogren syndrome, and Systemic lupus erythromatus (SLE)
SLE also known as lupus, is chronic autoimmune disease, that mainly affects joints, kidney, and skin.
Q. Common presenting symptoms fever, erythromatus rash to areas exposed to sunlight, weight loss, arthralgia (80-90%),
myalgia (50%). Rapid improvement in symptoms after discontinuing drug.
Drug induced lupus like syndrome: Drugs such as procainamide, chlorpromazine, and quinidine cause the production of
antinuclear antibodies against the histone dimer H2A-H2B. Hydralazine forms antinuclear antibodies to H1 and the H3-H4
complex. Drugs that cause drug induced lupus like syndrome usually take months to years before the associated symptoms
occur, whereas flares of SLE due to drugs may occur within hours to days.
Treatment: Q. Mild diseases, low fever, arthritis by NSAIDs and for Q. severe symptoms by oral methyl prednisone.
NSAIDs: PO;
Oxicams: piroxicam, meloxicam
Naphthalone: Nebutamine
cyclosporin tacrolimus. CYP3A4 and P-gp substrates
QAlerts!
26-year-old women had periodic symptoms of swelling on her left leg, lower back pain and strange tingling sensation in her
fingers and toes. She was assessed by several physician and many routinely dismissed as minor ailments. She was finally
diagnosed with lupus. She experiencing bouts of inflammation and attacking the body tissues and organs. What is the first line
therapy for arthritis associated with acute lupus symptoms?
A. Ibuprofen
B. Hydroxychloroquine
C. Hydrocortisone cream
D. Acetaminophen
Ans. A
Q May begin with fever and flu like symptoms and progress in to painful purple/red rash, HIGH FEVER, severe form of
erythema, skin peeling, and BLISTERS on the mucus membrane.
SJS also caused by certain infections such as hepatitis A, herpes, HIV or pneumonia.
Topical sulfa drugs are contraindicated because it may cause disease like SJS, this disease is life threatening. Treatment of SJS
is cortisone.
QAlerts!
A patient was clinically diagnosed as Steven Johnson syndrome after characteristic fever and mucus blisters on tongue and with
involvement of 10% body surface area. SJS is classically related to a medication hypersensitivity. What type of hypersensitive
reaction?
A. Type 1
B. Type 2
C. Type 3
D. Type 4
Ans. D
Ans. C
Detects antibodies against nuclear antigens (DS-DNA, SS-A, SS-B, histone). Positive results indicate autoimmune
disease rheumatoid arthritis.
what is pharmacogenetics →The study of pharmacogenetics allows designing and developing drugs that are
customized to each person’s genetic mark up.
Pharmacogenetics → study of drug response to genetic variability’s. Use of genetic analysis to predict drug response,
effi cacy, toxicity.
The most common drug metabolizing cytochrome enzyme?CYP3A4
Drugs that are substrate of CYP2D6? Codeine, duloxetine, atomoxetine.
References: Made especially for you. Pharmacogenomics and pharmacy practice, CPJ. Jan 2008 vol. 141, No.1
Questions Alerts!
Influenza (flu) viral infections. High-risk groups, flu season, and contraindications.
Hepatitis vaccinations. Hepatitis A and B, and Travelers.
Storage condition cold chain management (Biologics and vaccines).
Immunization is the means of providing specific protection against common and damaging pathogens.
Natural Immunity: Occurs when the person is exposed to a live pathogen, develops the disease, and becomes immune as a result
of the primary immune response.
1. Innate immunity
2. Adaptive or active immunity
3. Passive immunity
Active IMMUNITY Passive IMMUNITY
Q. Antigen enters the body and the body responds by Antibodies administered to provide short term or temporary
making its own antibodies and B-memory cells. immunity.
Slow onset (acting), is used for prophylaxis and long Fast acting and given pre-formed antibodies. Example newborn
duration of action. As soon as vaccine is administered gets from mom however wears off after some time. Temporary &
series immune reactions starts. short duration of action. Require booster dose. Administered im
or iv, or sc.
Example: Flu shot takes 2 wk to be effective and taken Example. Hepatitis B immune globulins (HBIG). Prophylaxis and
annually. therapy.
Pneumococcal vaccine takes 2 wks to be effective. Varicella zoster immune globulins (VZIG).
High-risk patient can take every 5 to 10 years.
Q. Rho (D) immune globulin (RhoGAM) prophylaxis for Rh +ve
Tetanus vaccine effective for 10 years. fetus by Rh –ve mother receives RhoGAM). Prophylaxis given
during pregnancy and after labor (delivery).
** QAlerts!
Active immunity is? Occurs when the hosts own body makes the antibodies and it own lymphocytes forms memory cells.
IgG pass/cross the placenta and enters baby blood stream is? Passive immunity
What is the difference between live and killed vaccine? live vaccine viruses are made less virulent.
Biological used as active immunity: Bacterial vaccine, bacterial antigen and toxoids.
Q. Measles, mumps, rubella (MMR), Chicken pox (varicella), Sabine Rabies, Typhoid (injected), cholera, and Shingrix (Shingle)
polio (oral), typhoid (oral),
Tuberculosis (BCG), yellow fever, small pox. Shingles
(Zostavax), Influenza inhaled (intranasal Mist).
Q.Live vaccines are contraindicated in pregnancy and HIV patients. Killed vaccine are can be given in pregnancy and
Avoid concurrent use with biological response modifiers (infliximab, immunocompromised.
anakinra, adalimumab, golimumab, certolizumab).
QAlerts!
(Internasal Influenza, Live varicella (chicken pox), BCG, rubella, oral polio, oral typhoid).
Pregnant woman with egg allergy take flu vaccine? given under doctor supervision
Subunit vaccine:
Toxoid
A gene inserted directly into a cell usually does not function, instead a carrier called vector is genetically engineered to deliver
the gene. Commonly used virus is Adenovirus. Example: AstraZeneca and Johnson & Johnson Covid-19 vaccine The drug,
Onasemnogene abeparvovec-xioi (Zolgensma, AveXis), is an adeno-associated virus vector-based gene therapy that targets
cause of spinal muscular atrophy (SMA) in children <2 years of age.
QAlerts! Viral vector vaccines are produced by? Integrating pathogen gene sequence in virus which is used as vector.
Flu vaccine
Given annual because viral structure changes every flu season. Q. Flu season in Canada and in “Northern hemisphere” is Oct
to April and Flu immunization season is Oct to mid-Nov.
Q. High risk group: seniors >65-year-old, asthma, COPD, CVD, diabetics, children >6 mo to 5-year-old, healthcare workers, and
pregnancy.
Q. Precaution: egg allergies (can administered in pharmacy), and with flu symptoms. All flu vaccine is killed vaccine, except Flu
Intranasal Mist. Precaution if patient have moderate to severe acute illness with or without fever, or have experienced
Guillain-Barre syndrome within 6 months.
Q. Guillain-Barrie syndrome is a heterogeneous condition with several variant forms that is the most cause of acute flaccid
paralysis in both children and adult. Patient typically complains of pain and weakness in limbs and tingling dysesthesias in the
extremities.
QAlerts!
Hepatitis vaccine
Hepatitis A Hepatitis B
Recommended Travelers’s endemic hepatitis A area House hold members with negative HBsAg and anti-HBs.
Pneumococcal vaccine
Strep pneumonia has 84 types/serotypes differ in their structure of polysaccharide capsules.Different serotypes result in to a
situation that essentially the same pathogen can cause disease many times in the same individual.Example: pneumococcal
vaccine is two types of vaccine polysaccharide and conjugate (polysaccharide conjugated to a protein carrier to enhance
immunogenicity). Pneu-P-23: a 23 valent capsular polysaccharide vaccine. Pneu-C-13: a 13 valent polysaccharide-protein
conjugated vaccine.
Q. Pneumococcal vaccine is indicated because it can reduce common pneumococcus pneumonia infections of community
acquired pneumonia, otitis media, bacterial meningitis, and prevent strep bacteria.
QAlerts!
Prevnar 13: 13 valent polysaccharide-protein conjugated vaccine induce antibodies by T-cell mechanism.
QAlerts!
Measles is caused by paramyxovirus. It spreads by normally direct contact or air. After coughing particles can stay about 2
hours in air. Can spread infection 4 days before symptoms.
QAlerts!
What to do, if patient comes at your pharmacy and express concern that some in people in his area have Measles infections?
Vaccine for Elderly Dosing Prevent Who will get
Influenza “flu” annually Seasonal flu (Influenza A and High risk; >65 yo, chronic conditions
B). (asthma, COPD, pregnant, CVD, DM).
Nov to April
Pneumococcal >65 yo older two vaccines Lung, blood, brain infections. >65 yo, cancer, immunocompromised,
COPD, DM, CVD, chronic alcoholics, HIV
infections.
Prevnar 13 and Pneumovax 23
Shingles Zostavax: single dose Painful rash with blister cause >50 yo and older
by shingles and this can lead
to pain called post herpetic
Zostavax (live)
neuralgia.
QAlerts!
During pregnancy avoid live vaccine (chicken pox, MMR) and however killed vaccine can use.
Flu or influenza vaccine recommended vaccine in all pregnancy women. Other vaccine that are recommended during
pregnancy are DTaP, hepatitis B, polio, pneumococcal and meningococcal.
QAlerts!
7. COPD 8. CVD
10. Children from the age of 6 months to 2 years 11. Egg allergies
Who is high-risk group for seasonal flu? (Pregnancy, children from 6 mo to 2 yrs, asthma, COPD, CVD, seniors >65 yo)
Who should not take flu vaccine? (<6mo, egg allergy and flu symptoms).
The type of acquired immunity whereby resistance to a disease is built by either having the disease or receiving a
vaccine to it. (Active immunity).
Who should not get live vaccines? (Pregnant and immuno compromised).
Flu vaccine effective against which type of viruses? (Influenza A and B)
Dukoral oral vaccine is in travellers to prevent (diarrhea associated with E. coli and Cholera infections).
Travelers to South East Asia, are recommended to take (Hepatitis A & B)
Rotavirus vaccine is used to prevent (stomach flu)
Gardasil vaccine is used against (Papilloma virus cervical cancer).
“FRY” the egg --> Flu, rabbis, yellow fever vaccine are prepared in egg.
Monocytes are white blood cells that can swallow and digest microscopic organisms and particles in a process known
as --> phagocytosis
Hashimoto is type of hypersensitivity? Type 2
Graves disease is? Hyperthyroid
Type 1 DM is? Autoimmune
Hepatitis B; for new born <48 hr, person exposed to hepatitis B like needle pricks <24hr.
Regular HepB schedule 0, 2, 6 month. For fast track 0, 21 days, 3mo. Booster q5y
Monocytes are white blood cells that can swallow and digest microscopicorganisms and particles in a process known as -->
phagocytosis
Hapten is --> Hapten is a low molecular weight compounds that act as immunogens after chemically complexing to a
larger molecule or cell surface.
Questions Alerts!
Common questions in pharmacy exam is to ask!
This chapter is focused on pharmaceutical products that are developed using recent biotechnological methods and their storage
conditions, and role of pharmacist.
Q.CYTOKINES
Cytokines are soluble protein molecules released by participating and interacting cells in the adaptive immune system.
Substances produced by some immune system cells to communicate with other cells.
Therapeutic cytokines involved in hematopoiesis, adaptive immunity, innate immunity, inflammation. Types of cytokines
includes;
Lymphokines Cytokines secreted by lymphocytes.
Interferons Cytokines secreted in response to viral infections or other stimuli.
Interleukins Cytokines secreted by some leukocytes and acts upon other leukocytes.
Chemokines Low molecular weight cytokines that affects chemotaxis and other aspects of leukocytes
behavior.
Tumor necrosis factors Peptides secreted by some macrophages and they induce necrosis of tumor cells and pro-
(TNF) inflammatory action.
Colony stimulating factors Erythropoietin’s
(CSF)
Interferon (involved in antiviral response)
Interferon are cytokine proteins that are secreted by cells when they become infected with virus. Q.Bind to nearby infected cells
and prevent viral infection. This increased resistance of cells to viral infection and slows the spread of disease.
Interferons
Alpha interferon (IFN-a) Q. Alpha interferon (IFN-) used for treatment of chronic hepatitis B (Peginterferon alpha
2a)
Beta Interferon
Q. Beta Interferon (fibroblast) is used for treatment of multiple sclerosis.
Gamma (immune).
Contraindications: Autoimmune disease (SLE, RA), severe depression, or
psychosis, neutropenia, thrombocytopenia and cardiac arrhythmias.
Hepatitis C is diagnosed by the presence of both hepatitis C antibody (anti-HCV) and HCV RNA confirms Hepatitis C infection.
QAlerts!
Interferon beta 1a is disease modifying therapy (DMT) is the first line treatment of? Multiple sclerosis
Interleukin
The majority is produced by T-helper cells and act as mediator between leukocytes.
Class I cytokine receptors IL-2, IL-3, IL-7, IL-11, IL-13, IL-15: A type of lymphokine that regulates the Q.growth and development
of white blood cells.
IL-3 Tcells/ and stimulate bone marrow stem cells causes B cell Hemopoietic growth factor are used for Thrombocytopenia
proliferation and mast cells.
Q. Manufactured by granulocyte colony stimulating factors (G-
G-CSF stimulates end cell functions and thereby CSF), Filgrastim (Neupogen), pegfilgrastim (Neulasta) used for
increase neutrophil count and activity. treatment of neutropenia.
IL-5 IL-5 promotes the activation of eosinophils. Used for uncontrolled severe asthma. Q. IL-5 inhibitor
is omalizumab.
IL-6 B & T cells/B lymphocytes/ stimulate B-cell differentiation.
IL-8 Macrophages/target Neutrophils, stimulate neutrophils and T
lymphocyte chemotactic growth factor.
IL-11 Secreted by Tcell. Induce megalocyte proliferation. Anemia, (hemopoietic growth factor), low platelets.
Q.Oprelvekin (interleukin-11)
The colony stimulating factors (CSF) stimulates the immune system may benefit patients undergoing cancer treatment. These are
glycoproteins produced via recombinant DNA technology.
CSF
Q.Filgrastim sc 5 mcg/kg QD for 7-10 days given after 24 h of chemotherapy to treat chemotherapy induced
neutropenia.
Sargramostim
Filgrastim and pegfilgrastim are contraindicated for patient with allergic to E. coli derived
proteins.
QAlerts!
Tumor necrosis factors are types cytokines and secreted by some macrophages and they induce necrosis of tumor cells and pro-
inflammatory action.
Adalimumab sc Cancer risk because TNF provides surveillance for some types of cancer so inhibiting can increase risk of cancers.
Etanercept,
ertolizumab, Congestive Heart Failure and multiple sclerosis because in patient with CHF the TNF myocardium expression is
upregulated and have elevated TNF levels in MS.
Golimumab
Granulomas: TNF is critical for granuloma formation and maintenance. Granulomas are host mechanism to
contain M. tuberculosis, thus TNF inhibition can increase risk of tuberculosis.
NON-TNF inhibitors:
Muromonab (orthoclone OKT 3 ): Indicated in acute graft rejection in renal, cardiac and hepatic transplant patients.
Omalizumab. Binds free IgE, reduces binding to mediator releasing cells (mast cells, basophil).
Hybridoma technology
Monoclonal antibodies are ultra-sensitive, hybrid, immune system derived proteins designed to recognise a specific antibody.
MAB are produced in quantity by growing the hybridoma in vitro (cell culture) or in vivo (eg. culturing in mice and collecting
ascites fluid).
Rule 2: 1 or 2 letters preceding –mab tell you the “source” of the antibody.
Rule 3: The 1 or 2 letters before the source tell you where the body the-mab works. Examples such as;
-c(i)-circulatory system
-k(i)- interleukin
-l(i)-immune system
-t(u)-tumor
Rituximab Omalizumab
Abciximab Daclizumab
Cetuximab
Basiliximab
-o- (all mouse) -xi- -zu- -U- human
Q. Chimeric antibodies: (antibodies with mixture of mouse and human component) are produced by Human AntiMouse
Antibody (HAMA) technology. Example of drugs produced by 5 chimeric antibodies: Rituximab, abciximab, infliximab,
cetuximab, basiliximab.
Q. Human antimouse antibody (HAMA) monoclonal antibody also known as chimeric antibodies.
Mouse (Murine) antibody: Example of drugs produced by murine antibody. Muromonab (Orthoclone OKT3), and capromab.
Humanized antibody: Example of drug produced by 12 Humanized antibodies (Human monoclonal antibodies from transgenic
mice). Q. Trastuzumab, omalizumab, and daclizumab.
Q. Trastuzumab (Herceptin): HER 2 -normal breast/stomach cancer cells consist of HER 2 receptors. These receptors signal to
grow and divide cells causing to cell grow too quickly. Trastuzumab inhibit HER 2 receptors.
Antisense therapy
(Antisense Oligonucleotide therapy)
Q. Antisense oligonucleotides are single strand of DNA or RNA that are complementary to chosen sequence. The antisense
RNA protein inhibits translation of certain "messenger RNA" by binding to them. The antisense DNA is used to target a specific
complementary RNA.
Q. Antisense drugs inhibit gene expression by oligonucleotide. Antisense therapy is used to treat b-thalassemia,
Cytomegalovirus CMV rhinitis, hemorrhagic fever virus, cancer, HIV-AIDS.
Q. In mechanism of action of antisense therapy acts on m-RNA and prevents translation.
Transcription Translation
Antisense Oligo
QAlerts!
Q. If researcher using template DNA sequence GTAA, which sequence would be used by researchers as an antisense
molecule? CATT
Biologics Biosimilars
Biologics are produced in living cells comprise of Biosimilar is highly similar to an approved reference biologic
complex proteins structure. and produced by entirely new process that can lead to small
differences in structure, stability, impurities and excipients compared
with reference biologics.
Biosimilars are similar to biologics but NOT identical, so they are NOT
Pharmacy substituting or switching biologic to
generally bio equivalent.
biosimilar require to follow provincial regulation.
QAlerts!
Biosimilar is? A biologic produced by difference process which is similar to reference biologic
Q. Cryo/ Lyoprotectants: replace water for hydrogen bonding, adsorb moisture from stoppers. Prevent over drying. eg. PEG,
sugars, mannitol, lactose, albumin.
Bulking agents: Give shape and elegance: eg. Mannitol, sorbital, glycine, arginine.
QAlerts!
Albumin is added to insulin formulation because? Lyoprotectant or collapse temperature modifier which helps insulin to stay
stable and extend affect of insulin.
QAlert!
Upstream à fermentation à separation à purification à formulation
Drug Delivery : Biotechnological based drug delivery systems formulated into liposomes ie., microscopic circular lipid particles
also known lipid nanoparticles.
Find answer
1. Infliximab 2. Etanercept 3. Megakaryoblast from the
table:
4. Hemophilia A 5. Muromonab-CD3 6. Erythropoietin's
Orthoclone OKT3
Questions Alerts!
Common questions in pharmacy exam is to ask!
Overdose symptoms of benzodiazepines, opioids, acetaminophen, tricyclic antidepressants and iron supplements.
Antidotes of overdoses of benzodiazepines, barbiturates, opioids, acetaminophen, tricyclic antidepressants, warfarin,
heparin, LMWH, digoxin, organophosphates, atropine and iron supplements.
This chapter focuses in methods of treatment associated with overdose of drugs and overdose symptoms, chemicals toxicity.
Drugs and chemicals that commonly cause toxicities, and the role of the pharmacist. Antidotes and treatment are presented for
specific drug toxicities.
Q. General management of toxicity
Poison prevention strategy
Child proof containers, constant vigilance, labelling and formulation.
GI Decontamination procedures
Decontamination consists of removal of any unabsorbed poison from the patient’s body.
Q. Commonly used methods include gastric lavage or gastric gabage, emesis, ipecac, adsorbent agent charcoal.
Gastric lavage or gastric gabage: This procedure can be used;
Emesis (vomiting)
This method is used to evacuate GI tract.
Emesis procedure is contraindicated in
Ipecac induced emesis and gastric lavage primarily removes substances from the stomach and their efficacy is affected by time
and quantity of ingestions. These procedures are more effective if they are implemented within 1 hour of ingestion.
Q. Syrup of Ipecac is administered within 60 min toxic dose ingestion (later has no benefit).
Adsorbent agent: Charcoal is good for drug and chemicals. NOT for (because not adsorbed) methanol, ethanol, iron, cyanide,
ethylene glycol, mercury, organic solvents, potassium, strong acids and bases. Do not use if patient is vomiting.
Dosage: Adults 25 to 100 g. Children 1 to 12 years 25 to 50 g, 0 to 1 years. 1 g/kg
Charcoal available as colloidal dispersion form.
Bowel Irrigation Method: Osmotic solution of polyethylene glycol (PEG) is used (1-2 liter /hr orally).
Enhancement of elimination. Enhancement of elimination is possible for a number of toxins, including manipulation of urine
pH to accelerate renal excretion of weak acids and bases.
Diuresis
Promotes elimination acids and bases. This can be alkaline and acid diuresis.
Alkaline Diuresis
Promotes the ionization of weak acids therefore prevents re-absorption by the kidney, facilitate excretion of weak acids.
Example salicylic acids, Q. ASA, phenobarbital, and barbiturates.
Q. NaHCO 3 side effects: Metabolic alkalosis, hypernatremia, hyper osmolarity and fluid overload.
Acid Diuresis
Used to promote elimination of weak bases. Example amphetamines, phencyclidines, quinidine derivative and alkaloid drugs.
Dosage: Ascorbic acid 500 mg to 1 g and ammonium chloride 4 g every 2 hours serum electrolyte and pH should be monitored.
Tricyclic Antidepressant (TCA)
Amitriptyline, Nortriptyline, imipramine, clomipramine, desipramine, doxepin, trimipramine
TCAs has one of the highest mortality rate any of the drug poisoning. Toxicity most commonly begins within 2 hours
of ingestion.
Overdose symptoms. TCA are extremely toxic in overdose. Consultation with poison control center is recommended.
Symptoms: Q. Mydriasis and anti-cholinergic symptoms, and Q. severe arrhythmias (AV node). (Cardiopulmonary
toxicity) exhibit tachycardia, QT prolongation.
Q. Treatment is symptomatic and supportive; arrhythmias and CNS involvement pose the greatest risk and may
occur suddenly; even initial symptoms appear to be mild.
Toxic dose is variable but in general 10 to 20 mg/kg may result in serious toxicity and may be lethal.
In child 50 mg dose can manifest the overdose symptoms.
There are 15% mortalities with overdose of TCA are reported. Toxicity begins within 2 hours of ingestion.
Initial symptoms are mild and can precipitate to CNS and cardiac symptoms. All cases of accidental, pediatric or
adult overdose
Q. Naloxone is available as intranasal solution, and IV, IM and SC injection. Recommended dose 0.4 to 2 mg, repeat
up to every 2-3 min as needed up to 10 mg.
Naloxone IV onset ~ 2 min; IM & SC onset 2 to 5 min.
Suboxone (buprenorphine + naloxone): used for opioid addiction treatment.
Methadone maintenance treatment (MMT) is used to treat opioid addiction treatment.
A customer of your pharmacy presents his prescription methadone. While he is waiting on reception area. He seems
unconscious and fell down. His medications profile in the past were Oxycodone, fentanyl and Tylenol # 3. Pharmacist
approaches to patient and determined that patient experiencing opioid overdose and has low respiration. What is the first
action a pharmacist would do?
Ans. D
Tips: If they fall, then call 911.
Acetyl Salicylic ACID (ASA) Overdose
Treatment: Acute symptoms of overdose should be treated by supportive therapy by removal of unabsorbed ASA from gut.
Management: Decontamination, alkaline diuresis, Hemodialysis. Q. ASA overdose is treated by NaHCO 3 diuresis.
Acetaminophen Overdose
In adult Q. hepatotoxicity may occur after ingestion of a single dose of more than 7.5 g (adults), or 150 mg/kg
(children).
A dose of 10 g or more is potentially fatal. However, reports have indicated hepatic necrosis with single dose of 6 g
and death occurring with single dose of 13 g.
Treatment: Consider consultation with poison control centers.
Clinical presentation of acute acetaminophen poisoning;
Q. Phase 1: Nausea, vomiting, GI bleeding and abdominal discomfort within 1 to 12 hr after ingestion.
Phase 2: Clinical improvement in seen in 6-24 hour of ingestion.
Phase 3: Metabolic acidosis, renal and hepatic failure, sepsis, pulmonary edema and death.
Q. Antidote N-acetylcysteine, it is administered within 8 – 10 hours of overdose.
Iron supplement overdose
(Fe fumarate 33%, Fe sulfate 20%, Fe. gluconate 12%).
Toxicity is based on the amount of elemental iron. Toxicity can occur at 60 mg/kg may cause GI symptoms.
Clinical overdose symptoms are nausea, vomiting, and bloody diarrhea, melena (BLACK STOOLS), hematemesis may
cause hemodynamic instability.
If GI symptoms does not occur within 6 hours of ingestion suggest, it is non-toxic dose.
Management: Decontamination for iron overdose should NOT be treated by charcoal. Treat by ipecac.
Q. Antidote is deferoxamine. Mechanism; it works by chelation.
Benzodiazepine
Benzodiazepine have a wide therapeutic index and taken alone in overdose rarely cause severe complication or fatalities.
Overdose with alcohol, barbiturates, opioids, TCA are dangerous.
Q. Antidote: Flumazenil, selectively reverse benzodiazepine effects. Flumazenil is a competitive partial agonist.
Overdose: Sedation, drowsiness, sleepy, confusion and ataxia.
Withdrawal symptoms
Insomnia, delirium and anxiety, autonomic hyperactivity (sweating, pulse >100 bpm), increased hand tremor, and restless.
Symptoms begin within 1-2 d of abrupt discontinuation or 5- 10 d for long acting.
Non-toxic drugs
Amoxicillin: 3 g daily maximum symptoms diarrhea.
10. Hydrochloroquine