Anemia

- RBC contains haemoglobin (Hb) which carries blood around the body
- Hb contains ferrous iron (Fe2+) – 1 Hb molecule can bind w 4 oxygen molecules
- Anemia causes low conc of oxygen around the body, leading to hypoxia
- Increases workload of lungs and heart
- Men: Hb level <13.5g/100mL and women: Hb level <12.0g/100mL

 MOA of Erythropoietin
- Hormone secreted by kidneys
- Stimulated proliferation and differentiation of RBC precursors which activates erythropoiesis
in hemopoietic tissues, thereby producing RBCs
- 200 billion RBCs are produced each day in a normal adult

 Uses of EPO
- Treats anemia caused by chronic renal failure, bone marrow disorders, chronic
inflammation, AIDS, cancers
1. Treats patients w low serum Erythropoietin levels

BANNED FROM INTERNATIONAL OLYMIC COMMITTEE

 Toxicity of EPO
- Hypertension
- Mild hypersensitivity
- Arthralgia
- Thrombus
- AV fistula
- Hyperkalemia
- Headache
- seizures

Necessary requirements for erythropoiesis

- Iron
- Vitamins: B12, B6, B1, C, E, riboflavin, pantothenic acid
- Folic acid (B9)
- Amino acids

 Causes of anemia
1. Decreased erythropoietin – renal disease, endocrine deficiency, starvation,
hemoglobinopathy
2. Inadequate marrow response to EPO – nutritional deficiencies, myelodysplasia, RBC
aplasia
 3. Increased erythrocyte loss – hemorrhage, hemolysis
4. Risk factors: poor socio-economic class, multiparity, teen pregnancy, menstrual
abnormalities

 Symptoms
- Fainting, fatigue
- Yellow eyes and skin
- Shortness of breath
- Muscle weakness
- Colour change in stool
- Chest pain, angina, heart attack
- Enlargement of spleen

 Types of anemia
- iron deficiency – loss of iron; women at risk (MOST COMMON)
- Megaloblastic – less intake of vitamin B12 and folic acid; bone marrow produces abnormal
RBC
- Pernicious – inability to absorb vitamin B12 in GIT (more common than megaloblastic)
- Hemorrhagic – loss of RBC through bleeding, stomach ulcers, menstruation etc
- Hemolytic – rupture of RBC plasma membrane due to parasites, toxins, antibodies etc
- Thalassemia – genetic defect in Hb synthesis (malformed RBCs)
- Sickle cell – RBCs have an abnormal, rigid and sickled shape (hereditary)
- Aplastic – destruction of red bone marrow by toxins, gamma radiation etc

 Treatment
2. Hematopoietic growth factors – Erythropoietin
- Glycoprotein
- Originally purified from urine of patients w severe anemia
- First human hematopoietic growth factor to be isolated
3. Recombinant human Erythropoietin (rHuEpo)
4. Erythropoietin
- Epoetin alfa: standard rHuEpo (admin 3x a week)
- Darbepoetin alfa: modified EPO with longer half-life (admin weekly)
- Methoxy polyethylene glycol-epoetin beta: isoform of EPO attached to polyethylene glycol
polymer (admin single IV or SC 2x a week or monthly)

IRON DEFICIENT ANEMIA

Iron:

- Absorption: duodenum and proximal jejunum

- Excretion: bilirubin
- Also known as microcytic hypochromic anemia
 - Poikilcytosis is seen in severe anemia

 Treatment
1. Oral therapy – ferrous sulphate, gluconate, fumerate (2-3mg/kg)
- Side effcts: nausea, epigastric discomfort, abdominal cramps, constipation/diarrhea
2. Parenteral therapy (IV or IM) – iron dextran, iron sodium gluconate complex, iron sucrose
(20-40ml/day)
- Side effects: local pain, tissue staining (brown), headache, fever, nausea and vomiting,
urticaria, back pain
- Given to patients who cannot absorb oral iron or with excessive chronic blood loss
- SHOULD NOT BE GIVEN IN HEMOLYTIC ANEMIA OR THALESSEMA due to increase of iron
storage

VITAMIN B12 (Cobalamin)

- Produced by bacteria and can’t be synthesized by multicellular organisms

- Absorbed in distal ileum by pinocytosis
- Essential for the conversion of homocysteine to methionine in the cytosol and the
conversion of methyl malonyl-CoA to succinyl-CoA in the mitochondrion

 Deficiency
1. Folic acid deficiency
- methyl malonyl-CoA accumulates and causes neurologic disorders
- No formation of THF
2. Lack of methionine – senile graying of hair due to build up of hydrogen peroxide in
follicles which reduces effectiveness of tyrosinase
3. Megaloblastic anemia – inhibition of DNA synthesis in RBC production

 Symptoms of deficiency – dizziness, depression, pale skin, sore tongue, palpitations, memory
and weight loss, hallucinations, muscle weakness, digestive issues, fatigue, shortness of
breath, unable to pee, tingling in toes and fingers

 Causes of deficiency – pernicious anemia, /Addison-biermer’s anemia, gastrectomy,

achlorhdria-induced malabsorption, bacteria in small bowel (rare), chronic pancreatitis
(rare), thyroid disease (rare)

 Treatment – hydroxycobalamin (preferred because high PPB and remains in circulation

longer) 1mg po, 1-2mg/day po, IM

FOLIC ACID (Vitamin B9)

- Natural form: folacin and folate

- Aqueous form: Pteroyl-L-glutamic acid and Pteroyl-L-glutamate
- Converted to dihydrofolic acid in liver then tetrahydrofolate
- Absorbed in proximal jejunum; wide distribution; metabolized by demethylation; excreted
via kidneys

- Folate deficiency usually presents as a megaloblastic (macrocytic) anemia

 Causes of Deficiency
- Low intake of folates
- Alcoholics
- Patients w liver disease
- Patients who require renal dialysis
- Phenytoin, oral contraceptives, isoniazid, methotrexate, trimethoprim, pyrimethamine
- Pregnancy
- Patients w hemolytic anemia
- Some cancers, leukemia, certain skin disorders

 Symptoms
- Fatigue
- Gray hair
- Mouth sores and swollen tongue
- Depression
- Loss of memory and appetite
- Trouble concentrating
- Birth defects
 - Poor growth

 Treatment
- Improved diet
- 1mg/day folate to reverse megaloblastic anemia
- Parenteral (rare)

Anxiolytics, Hypnotics and Sedatives

Erectile Dysfunction and Benign Prostatic Hyperplasia

- 30-40% of men and women (increases with age)

- Impotence (ED): inability to acquire or maintain an erection for sex
- Diminished libido: a lack of interest in sex
- Premature/ delayed/ inhibited ejaculation

Male reproductive system

- The 2 endocrine glands that develop in the male are called the testes. This produce sperm as
well as the hormone testosterone.
- Vas deferens, which stores produced sperm and carries sperm from the testes
to be ejaculated from the body
- The prostate gland which produces enzymes to stimulate sperm maturation as well as
lubricating fluid
- The penis, which includes 2 corpora cavernosa and corpus spongiosum, that allow massively
increased blood flow and erection
- The urethra, through which urine as well as sperm and seminal fluid are delivered.

 MOA of erections
- Stimulation of shaft by nervous system secretes NO – synthesizes cyclic guanosine
monophosphate (cGMP) which causes vasodilation
- Phosphodiesterase type 5 (PDE5) destroys cGMP – vasoconstriction of erectile tissue

ED

- Diabetes is the MOST COMMON cause of ED in men (50-60%)

- Risk factors: smoking, lack of exercise, obesity
- Associated with symptoms of depression

 Causes
1. Primary ED
- Guilt
- Fear of intimacy
- Depression
- Severe anxiety
2. Secondary ED
- Vascular disorders (atherosclerosis of penile arteries)
- Neurologic disorders
- Complications of prostate surgery
- Clonidine, b-blockers, loop diuretics, alcohol, cocaine, anticholinergic drugs, anticancer
drugs, antiandrogens
 3. Psychological causes
- Fatigue
- Stress
- Performance anxiety
4. Major Depressive Disorder (MDD)
5. Physical causes
- Urological
- vascular,
- neural
- endocrine (hypogonadism or hyperprolactinemia)
- latrogenic pelvic trauma

PDE5 inhibitors – Sildenafil (Viagra), Tadalafil, Vardenafil

- MOA: inhibits PDE5 by binding to active site and prevents the hydrolysis of cGMP (cGMP)
accumulates and prolongs vasodilation)
- SEXUAL STIMULATION IS REQUIRED FOR ACTIVATION
- NO is produced by macrophages and is used in the immune system to impair DNA synthesis
and metabolism in microorganisms

 Sildenafil (Viagra)
- Most popular and oldest
- 25, 50, 100mg to be taken 1hour before sex
- DOA: 30mins – 4-5hours (up to 12 hours)
- Once a day
- Side effects: headache, dizziness, facial flushing, abnormal vision

 Sildenafil vs cGMP
- Sulfur dioxide group of sildenafil mimics phosphate in cGMP
- Both have similar 4-piperidone rings

 Tadalafil (Cialis)
- Oral 10 and 20mg 2hrs before sex
- DOA: 36hours (longest)
- Once a day
- Side effects: headache, back pain, flushing

 Vardenafil (Levitra)
- Higher potency and rapid binding to PDE5 causing slower dissociation from receptor
compared to other inhibitors
- 5, 10 and 20mg
- Once daily
- DOA: 30mins – 4-5hours
- Side effects: flushing, rhinitis, headache
Apomorphine HCl (Urima)

- Centrally acting drug that improves ED by enhancing neural erectile signals

- Non-selective dopamine receptor agonist and acts on D2-like receptors in brain
- Dopamine increases heart rate and blood pressure
- Fast acting (20 mins)
- Side effects: nausea

 Alprostadil
- Causes vasodilation and increases blood flow throughout body
- More effective when used with phentolamine (non-selective alpha1 antagonist) and
papaverine (tri-mis combo therapy 92%)
- Papaverine MOA: inhibits PDE enzymes and modulates calcium signaling
- PAPAVERINE AND ALPROSTADIL ARE MAIN DRUGS USED FOR INTRACAVERNOUS
TREATMENT
- Alprostadil – vasoactive prostaglandin E1
- Onset of action: immediate
- Side effects: penile pain, prolonged erection, priapism and fibrosis
- AVAILABLE AS CREAM – BEFAR

 Caverject – direct injection of papaverine/ Alprostadil

 MUSE – intraurethral pellets inserted down the opening of penis with a minute insertion
stick
 Befar – topical cream of Alprostadil (only available asia)
 Triple mix – prostaglandin E1 + papaverine + phentolamine

BENIGN PROSTATIC HYPERLASIA (BPH)

- BPH: a benign overgrowth of prostate tissue pushes against the urethra and bladder,
blocking the flow of urine
- Also called benign prostatic hypertrophy
- Occurs in older men
- caused by over production of DHT

 Causes
- Testosterone
- Obesity
- Diabetes
- Lack of physical activity
 Symptoms
- Difficulty urinating
- Frequent urination (particularly at nights)
- Weak urine system
- Strain during urination

 Treatment
- Removal of prostate
- TUNA (Transurethral Needle Ablation of the Prostate) is a technique that uses low radio
frequency energy delivered through 2 needles to destroy excess prostate tissue
- TUMT (Transurethral Microwave Thermotherapy) uses small microwave antenna through
the tip of the penis into the urethra.
- Prostatic stent is a stent used to keep open the urethra and allow the passing of urine in
cases of prostatic obstruction and lower urinary tract symptoms (LUTS)

Alpha1 blockers (Tamsulosin, Terazosin, Doxazosin, Alfuzosin, Silodosin)

 MOA
- Alpha1 blockers relax smooth muscles in prostate and the bladder neck, thus increasing
urine flow
- Alpha1 receptors are on bladder

 Side effects
- Inhibits ejaculation
- Orthostatic hypotension/ postural hypotension – BP suddenly falls when the person stands
up
- Nasal congestion

5 alpha-reductase inhibitors

 MOA:
- Inhibits 5alpha-reductase which inhibits the production of dihydro-testosterone (DHT)
- DHT is a metabolite of testosterone that is responsible for growth of prostate
- Reducing levels of DHT causes alopecia

 Side effects
- Impotence
- Decreased libido
- Decreased ejaculation
- Gynecomastia
Prostate cancer

 Symptoms – urinary retention, painful urination

 Diagnosis
- Rectal exam
- Ultrasound of testicles, prostate and kidneys
- Prostate specific antigen test (PSA) – levels above 4ng/mL

NSAIDs
General & Local Anesthetics

 Anesthesia – reversible condition of comfort, inactivity and physiological stability (inability to

perceive pain) in a patient before, during and after a procedure
- Patient unresponsive to painful stimuli

 General anesthetics are CNS depressants while local anesthetics block the conduction of
pain impulses to the spinal cord

Pre-anesthetic medications

 Uses
- Relieves apprehension
- Relieves anxiety
- Improve speed and smoothness of induction
- Provide analgesia and amnesia
- Counteracts parasympathetic effects of anesthesia
- Inhalation – for maintenance (controls depth of anesthesia)
- Intravenous – for induction and short procedures

 Types
1. Sedative and anxiolytic agents
- Barbiturates eg pentobarbital
- BZDs eg diazepam, lorazepam, midazolam
2. Antiemetics and allergies
- Antihistamines eg loratadine
- Butyrophenones eg Droperidol
3. Anticholinergics
- Atropine
- Hyoscine (also has antiemetic effects)
4. Analgesics
- Opioids eg pethidine, fentanyl

 Stages of anesthesia
Stage 1: conscious sedation – analgesia
Stage 2: excitement/disinhibition: - delirium, amnesia, enhanced reflexes, irregular
respiration, involuntary salivation, defecation, retching and vomiting
Stage 3: surgical anesthesia – loss of consciousness, inhibition of spinal reflex, no pain,
regular respiration and blood pressure is normal
Stage 4: Medullary depression: - severe CNS depression, depression of respiration and
vasomotor nuclei in brainstem; causes death; SHOULD NEVER BE REACHED
 General anesthetics
Inhalation Intravenous
Non-halogenated: Nitrous oxide gas Barbiturates, BZDs, propofol, Dissociative,
Opioids
Halogenated hydrocarbon: desflurane,
enflurane, halothane, isoflurane, sevoflurane

No longer used agents: diethyl ether,

chloroform, cyclopropane (highly flammable
and slow induction with unpleasant stages)

Inhalation anesthetics

 Rate of induction depends on:

- Pulmonary ventilation rate
- Alveolar partial pressure (conc of anesthetic in inspired air)
- Rate of increase partial pressure of anesthetic in blood (blood/gas partition coefficient)
- Alveolar blood flow
- Arteriovenous conc gradient
- Solubility (determined by blood/gas P) – determines speed of induction

 Blood/Gas Partition Coefficient

- The ratio of concs of anesthetics in blood and gas phases at equilibrium
- Represents the capacity of blood or a specific tissue to absorb the anesthetic
- LOWER BLOOD/GAS P, FASTER THE INDUCTION AND RECOVERY (eg Nitrous oxide)
- HIGHER BLOOD/GAS P, HIGHER THE UPTAKE OF GAS INTO BLOOD AND SLOWER THE
INDUCTION (eg Halothane)

 Oil/Gas Partition Coefficient

- Measures lipid solubility (how potent an anesthetic is)
- HIGHER THE LIPID SOLUBILITY THE MORE POTENT THE ANESTHETIC (eg Halothane)
- MAC: Minimum Alveolar Conc – measures potency of inhaled anesthetic
- MAC = 1.3/oil:gas P
- Potency = 1/MAC
- MORE LIPID SOLUBLE THE ANESTHETIC, THE LOWER MAC AND GREATER POTENCY

 MOA
- Binds to GABA receptors on Cl ion channels
- Increases influx of Cl and efflux of K from neurons (causes hyperpolarization)
- Reduces Na and Ca influx (inhibits neuronal firing)
- Stimulates the action of GABA @ GABAa receptors
- Disrupts neuronal membrane proteins and sensory processing in thalamus (loss of
consciousness and analgesia)
- Inhibits neuronal output from internal pyramidal layer of cortex (reduces motor activity)
 Halothane
- Prototype halogenated compound
- Very potent
- Slow induction and recovery
- Relaxes skeletal muscle and smooth muscles on bladder
- Lowers HR, CO and BP
- MAC: 0.75%
- Risk of arrhythmias
- Side effects: severe hepatoxicity

 Enflurane
- MAC: 1.7%
- Moderate induction and recovery
- Decreases CO and BP, and respiratory function
- CNS excitation @ high conc – epileptic seizures during induction or recovery
- Relaxes skeletal muscles and bladder

 Isoflurane
- MAC: 1.2%
- Moderate induction and recovery
- Almost all drug is exhaled
- Maintains general anesthesia
- Reduced myocardial depression than halothane
- Hypotension

 Desflurane
- MAC: 6%
- Rapid induction and recovery
- Causes airway irritation – coughing and bronchospasm
- Moderate muscle relaxation
- Hypotension
- Eliminated unchanged in exhaled air

 Sevoflurane
- MAC: 1.9%
- Rapid and smooth induction and recovery
- Little toxicity
- Adequate muscle relaxation
- Used as general anesthesia for children (does not irritate airways)
  Nitrous oxide (laughing gas)
- MAC: 100%
- Rapid and smooth induction and recovery
- Low potency (used in combo)
- Uses: minor surgeries, dental procedures, reduces pain in uterine contractions
- Good analgesic
- Non-flammable (combustible) and non-irritating
- Induces mild euphoria
- Chronic use may cause megaloblastic anemia

 Malignant hyperthermia
- In predisposed individuals, exposure to IA (except nitrous oxide) causes release of muscle Ca
stores causing tonic muscle contraction and then life-threatening hyperthermia, acidosis and
breakdown
- Seen with depolarizing muscle blockers (eg succinylcholine)
- Treated with dantrolene (muscle relaxant that blocks Ca channels)

Intravenous Anesthetics

 Induces anesthesia within secs

 Rapidly crosses BB due high lipid solubility

 Barbiturates – thiopental, methohexital (ultra-short acting)

- Rapid induction (15-3 secs)
- DOA: 5-10 mins
- MOA: Enhances activity of GABA by prolonging opening of Cl channels
- No analgesia
- No effect on skeletal muscles
- Reduces cranial blood flow (decreases increased intracranial pressure – ICP)
- MOA: prolonged opening of GABAa Cl channels
- Side effects: hypersensitivity, accumulation in fat and muscles (hangover), respiratory
depression, tolerance
- Sudden withdrawal: grand mal seizures, tremors, vivid hallucinations, psychosis
- Acute toxicity: renal failure, CVS collapse, severe respiratory depression, NO ANTIDOTE
- Drug interactions: enzyme induction
- Contraindications: respiratory depression, severe hepatic disease, pregnancy

 BZDs – diazepam, lorazepam, midazolam

- MOA: increases frequency of opening GABA Cl channels
- Produces slow onset of CNS effects compared to barbiturates
- Produces high incidence of anterograde amnesia
- ANTIDOTE: Flumazenil
  Opioids – fentanyl, sufentanil, alfentanil, remifentanil
- Not potent anesthesia
- Potent analgesic
- ANTIDOTE: Naloxone, Naltrexone

 Ketamine
- MOA: blocks action of glutamate @ NMDA receptors
- Causes dissociative anesthesia
- Good analgesic
- DOA: 5-10 mins for IV and 12-25 mins for IM
- May increase BP, causes hallucinations, vivid dreams, irrational behaviour on recovery
- Causes bronchodilation

 Propofol
- Di-isopropyl phenol compound
- DOA: 5-10 mins for IV and 12-25 mins for IM
- Rapidly metabolized and eliminated
- No analgesic effect or muscle relaxation
- Causes respiratory and myocardial depression
- Anti-emetic
- Reduces cranial blood flow (decreases increased intracranial pressure – ICP)

 Etomidate
- Rapid induction in patients w limited cardiovascular reserve
- DOA: 5-10 mins IV
- Low cardiovascular risk
- Does not affect BP
- No analgesic effect or muscle relaxation
- May cause adrenal suppression, therefore not admin by infusion

Local anesthetics

 MOA
- Inhibits voltage-gated Na channels of excitable membranes
- Blocks the transmembrane pore of voltage Na channels in excitable cells, preventing Na
conductance
- Prevents depolarization
- Produces non-specific, reversible blockade of neuronal action potential conduction without
the loss of consciousness
 LA are weak bases (pKa: 8-9) and are mainly ionized @ physiological pH
 Alkaline intracellular pH: INCREASED unionized drug and INCREASED LA lipid solubility
 Acid intracellular: INCREASED ionized drug; INCREASED binding to Na channels; blockade
 Esters Amides
Cocaine, procaine, tetracaine, benzocaine Lidocaine, bupivacaine, prilocaine, ropivacaine
- Short DOA - Longer plasma half-life
- Inactivated in plasma & tissues by non- - Less vasodilation potential
specific esterase - Greater potency
- High vasodilation potential - Low allergic potential
- Allergic rxn - Metabolized in liver (more stable)

ESTERS

 Procaine
- First safe agent used
- Low potency
- Slow onset, short DOA
- Only used for infiltration anesthesia

 Benzocaine
- low solubility in water
- ONLY USED TOPICALLY
- Treats: hemorrhoids and sunburns (stops itching and pain)

 Cocaine
- Increases circulation of catecholamines (causes vasoconstriction)
- ONLY USED TOPICALLY AS 1%, 4% OR 10% SOLUTION

 Tetracaine
- Long DOA
- Popular for spinal and corneal anesthesia

AMIDES

 Lignocaine
- Most used
- Faster, greater potency and longer DOA than procaine
- Rapid absorption
- Mainly used as vasoconstrictor

 Bupivacaine
- Long DOA
- Popular for labour anesthesia
  Prilocaine
- Moderate DOA
- Very little vasodilation
- Causes methemoglobinemia due to production of toluidine during metabolism
- Limited use in obstetrics due to neonatal methemoglobinemia

Voltage Na Channels

1. Resting: Na channels are CLOSED and no ions are allowed to pass through
2. Activated: Na channels are OPEN and ion influx occurs
3. Inactivated: Na channels become saturated (prevents further Na from entering cell)

Step 1: increase the threshold or firing level

Step 2: decrease rate of action potential (slows depolarization) = reduction of firing rate

Step 3: increase action potential duration (prolongs repolarization)

PHARMACOKINETIS OF LA

 Administration
1. Topical – mucus membranes (nose, mouth, throat)
- Tetracaine (2%)
- Lignocaine (2-10%)
- Benzocaine (20%)
- Cocaine (1 – 4%) has excellent penetration and local vasoconstrictor effects

2. Infiltration injection
- Peripheral nerve endings (major nerves)
- Epidural or subarachnoid spaces surrounding spinal cord

3. IV
- Will affect other tissues
- Short surgeries (<60 mins) involving extremities

 Absorption
- Physiochemical properties of drug
- Dosage
- Site of injection
- GREATER THE LIPID SOLUBILITY, GREATER THE PENETRATION, GREATER POTENCY
- Sodium bicarbonate maximizes mount of drug in unionized form, therefore increasing onset
of action

 Distribution
1. Tissue blood flow
- Disposition in highly perfused organs – brain, liver, kidney, heart
- Slower distribution to low perfused organs – muscles, fat, bones. GIT
- Short plasma half-life
- Use of vasoconstrictors – epinephrine, phenylephrine
- GREATER THE PROTEIN BINDING, THR LONGER THE DOA
- Short-acting DOA: procaine and chloroprocaine
- Intermediate DOA: lidocaine, mepivacaine, articaine (dental), prilocaine
- Long-acting DOA: tertracaine, bupivacaine, levobupivacaine, ropivacaine

 Metabolism and elimination

1. Esters
o hydrolyzed rapidly in blood by circulating plasma pseudocholinesterase to inactive
metabolites (except cocaine – hepatic metabolism)
2. Amides
o hydrolyzed by liver microsomal CYP450
o prilocaine > lidocaine > mepivacaine > ropivacaine > bupivacaine & levobupivacaine

- excreted in urine

 Adverse effects
- CNS: drowsiness, light-headedness, agitation, confusion, visual and auditory disturbances,
convulsions, respiratory depression
- CVS: myocardial depression and vasodilation – hypotension
- Hematologic effects
- Hypersensitivity
- High doses: nystagmus, muscular twitching, convulsions
- Methemoglobinemia
- Tachyphylaxis (rapid development of tolerance)
- PREGNANCY INCREASES TOXICITY

 Pain classification
1. Physiology
o Nociceptive – sharp, aching or throbbing pain caused by damage to tissues
o Neuropathic – pain due to nerve damage
o Inflammatory – activation and sensitization of nociceptive pain by mediators
released at site of inflammation

2. Site
o Somatic – nociceptive pain; skin pain; tissue pain; muscle pain
o Visceral – nociceptive pain for internal organs

3. Severity
o Mild: <4/10
o Moderate: 5/10 or 6/10
o Severe: >7/10

4. Duration
o Acute - pain of less than 3 to 6 months duration.
o Chronic - pain lasting for more than 3-6 months
Antipsychotics

 Schizophrenia
- a group of disorders involving disruption of thought and disintegration of personality
- etiology: unknown or excess dopamine or serotonin activity in brain
- Positive symptoms: hallucinations, delusions, thought disorders, insomnia, disorganized
speech
- Negative symptoms: alogia, apathy, anhedonia, inattentiveness, amotivation, social
withdrawal

 Antipsychotics
- Neuroleptics, major tranquillizers
- MOA: DA blocker
- Classification: phenothiazines, Butyrophenones, Dibenzoxazepines, Thioxanthines, Atypical
- Drug choice depends on potency and side effects

1. First generation
- Chlorpromazine
- Loxapine
- Fluphenazine
- Haloperidol

2. Second generation
- Clozapine
- Risperidone
- Paliperidone
- Quetiapine
- Olanzepine
- Ziprasidone
- Luprasidone

3. Third generation
- Aripiprazole

Phenothiazines Butyrophenones Dibenzoxazepines Thioxanthines Atypical

Chlorpromazine Haloperidol Loxapine Thiothixene Clozapine
Fluphenazine Droperidol Risperidone
Perphenazine Olanzapine
Quetiapine
Ziprasidone
Aripiprazole
  SEROTONERGIC ACTIVATION INHIBITS DA RELEASE while DA BLOCKADE CREATES
IMBALANCE WITH HIGHER SEROTONERGIC ACTIVITY
 Dopamine pathways are responsible for: pleasure, motor function, compulsion,
perseveration
 Serotonin pathways are responsible for: mood, memory processing, sleep, cognition
 Mescortical pathway mediates negative and cognitive symptoms
 Mesolimbic pathway mediates positive symptoms
 Nigrostriatal pathway controls movement
 Tuberoinfundibular pathway controls prolactin release

Typical antipsychotics

 MOA:
- blocks DA2 receptors in mesolimbic dopamine pathway
- blocks DA receptors in nigrostriatal pathway and causes Parkinson’s symptoms
(akinesia/bradykinesia, rigidity and tremors)
- DA blockade in pituitary causes prolactin release with milk production and amenorrhea
- DA blockade in basal ganglia (striatum) results in movement disorders
- Relieves positive symptoms but increases negative symptoms (neuroleptic induced
syndrome caused by dopamine-serotonin imbalance)

 Potency vs affinity
- POTENCY IS PROPORTIONAL TO D2 AFFINTY
- Haloperidol, thiothixene high potency w high affinity for D2 receptors
- Chlorpromazine and thioridazine low potency from low affinity for D2 receptors

 Phenothiazines
1. Chlorpromazine
- Blocks D2 receptors greater than 5-HT2A receptors
- Alpha receptor blocker
- Muscarinic receptor blocker
- H1 receptor blocker
- CNS depressor (sedation)
- Decreases seizures

2. Thioridazine
- Pigmentary retinopathy
- Cardiac arrhythmias and QT prolongation