Arterial blood gas and acid base balance

Buffer system : in the body, more than 13,000 mEq of acids are produced daily in the metabolism
(organic acids, inorganic acids, and CO2)

Most of these acids are eliminated by the lungs ( Coq) and the rest is excreted by the kidneys (titrable

BUFFER S

1. PROTEIN BUFER IN BLOOD PLASMA

a. Made up of amino acids which contain positively charged amino groups and negatively
charged carboxyl groups
b. The charged region of these molecules can bind hydrogen (H+) and hydroxyl ions (OH)
c. 2/3 of the buffering power of the blood and most of the buffering in cells
2. Hemoglobin
a. Principal protein inside of RBC
b. During the conversion of CO2 into HC)3, hydrogen ions liberated in the reaction are
buffered by hemoglobin, which is reduced by the dissociation if oxygen
3. Phosphate buffer system
a. Exchange of sodium in the urine hydrogen ion filtrate
4. Bicarbonate-carbonic acid buffer
a. Most extracellular blood buffer
b. Importance:

i.
ii. Changes in CO2 modify the ventilation (respiratory rate)
iii. HCO3 concentration can be altered by the kidneys

Organs for the regulation of acid-base balance

1. Lungs

• Control of CO2 concentration

• Rapid and sensitive in adjusting blood pH nut short term only

2. Kidneys

• Reclaims HCO3 from the glomerular filtrate by excretion of acids

• Slow in response but compensation is complete and long term

HENDERSON- HASSELBACH EQUATIN

• It expresses acid-base relationship and relates the pH of a solution to the dissociation properties
of the weak acid
• Bicarbonate to carbonate ration (20:1)
•
 •
• Where:
o pKa = 6.1 (combine hydration and dissociation constants for CO2 in blood)
o Conjugate base= bicarbonate
o Weak acid= carbonic acid

Parameters in assessment of Acid-base Balance

pH measurement:

• Normal pH: 7.35 – 7.45

• Acidosis: <7.35
• Alkalosis: >7.45

Evaluation of ventilation

• Normal PCO2: 35-45 mmHg

• Respiratory alkalosis: < 35 mmHg
• Respiratory Acidosis: >45 mmHg

Increase of heparin = increase pCO2 (12-15%)

Total CO2 = dissolved CO2 = H2co3 = HCO3

Increased pCO2: use of elicit drugs (barbiturates, morphine and alcoholism)

Evaluation of metabolic process

• Normal HCO3: 21-28 mEq/L

• Metabolic acidosis: <21 mEq/L
• Metabolic alkalosis: >28 mEq/L

Evaluate degree of oxygenation

• Normal PO2: 81-100 mmHG (adequate oxygenation)

• Mild Hypoxemia: 61 – 80 mmHg
• Moderate Hypoxemia: 41-60 mmHg
• Severe: 40 mmHg or less
• Note: healthy persons in higher altitudes will show lower ranges of arterial pO2 because of the
naturally lower partial pressure of oxygen in the atmosphere
• pO2: 60-70% lower in venous blood after oxygen is released in the capillary tissues
• The degree of association or dissociation of oxygen with hgb is determined by PO2 and the
affinity of hgb for O2
• Low PO2: seen in MI, interstitial pneumonia, severe congestive failure
FOUR BASIC ABNORMAL STATES

1. Metabolic acidosis
a. Is caused by bicarbonate deficiency
b. Seen in DKA, lactic acidosis (alcoholism), renal failure, diarrhea
c. Causes greater potassium efflux than respiratory acidosis
d. Causes: inorganic acids causes grater potassium efflux (H2SO4, HCL) and organic
acids (lactic acids, keto acids)
e. ELECTROLYTE IMBALANCE: hypokalemia and hyperchloremia
2. Metabolic alkalosis
a. Causes by bicarbonate excess
b. Seen in vomiting (chloride loss in the stomach)
c. Compensation is least effective (because hypoxemia stimulates ventilation)
d. ELECTROLYTE IMBALANCE: hypokalemia and hypochloremia
3. Respiratory acidosis
a. Due to excessive carbon dioxide accumulation
b. Seen in : chronic obstructive pulmonary disease, myasthenia gravis, CNS disease,
drug overdose, botulism, stroke, myxedema, pneumonia
c. HCo3 rises 1 mEq/L for each 10 mmHg rise in PCO2
d. ELECTROLYTE IMBALANCE: hypokalemia
4. Respiratory alkalosis
a. Due to excessive carbon dioxide loss
b. Observed during: anxiety, severe pain, aspirin overdosage, hepatic cirrhosis, gram-
negative sepsis, salicylate, and progesterone drugs
c. Compensation is most effective
d. HCO3 falls 2 mEq/L for each 10 mmHg fall in PCO2
ACTIVITY NO.16: ELECTROCHEMISTRY PRINCIPLES OF
BLOOD GAS ANALYSIS
BLOOD GAS ANALYZERS: pH, pCO2, and pO2
• Blood gas analyzers use electrodes as sensing
devices to measure pO2, pCO2, and pH.
• pO2= Amperometric
• pCO2 and pH= Potentiometric
Definition of terms
• Cathode- a site to which cations tend to travel
at which reduction occurs
• Reduction- the gain of electrons by a particle
• Anode- a site to which anions migrate at which
oxidation occurs.
• Oxidation-loss of electrons by a particle
• Electrochemical cell-formed when two opposite
electrodes are immersed in a liquid that will
conduct the current.
Measurement of pO2
• Clarke electrodes (pO2 electrodes)
o Measure the amount of current flow in
a circuit that is related to the amount of
O2 being reduced at the cathode
Sources of error:
• Primary source of error is associated with the
build up of protein material on the surface of
the membrane.
• Bacterial contamination within the measuring
chamber
• Incorrect calibration
Measurement of pH
• To measure how much force/energy/potential a
given ion possess:
• 2 electrodes: measuring electrode responsive to
the ion of interest
• Reference electrode
• Voltmeter- which measures the potential
difference between the 2 electrodes.
• The potential difference is related to the
concentration of the ion of interest by Nernst
equation:
• To measure pH, a glass membrane sensitive to
H is placed around an internal Ag-AgCl
electrode to form a measuring electrode.
• Potential=Unknown H and cH=proportional
• For the potential developed at the glass
membrane to be measured, a reference
electrode must be introduced into the solution
and both electrodes must be connected to a pH
(volt) meter
• The reference electrode provides a steady
reference voltage against which voltage
changes from measuring electrode are
compared. E.g., Calomel (Hg-HgCl), Ag-AgCl
(half cell)
Measurement of pH and pCO2
• The pH meter reflects the potential difference
between the 2 electrodes
Measurement of pCO2
• pCO2 is determined with a modified pH
electrode called Severinghaus electrode
• An outer semipermeable membrane that allows
CO2 to diffuse into a layer of electrolyte covers
the glass pH electrode
• The CO2 that diffuses across the membrane
reacts with the buffer, forming carbonic acid,
which then dissociates into bicarbonate plus H.
• The change in the activity of H is measured by
the pH electrode and related to pCO2
PRE ANALYTICAL CONSIDERATIONS
• Knowledgeable and well experienced
phlebotomist.
• The choice of artery- radial, brachial, femoral,
or temporal
• Venous sample- if pulmonary function or O2
transport is not being assessed
• Ideal collection device: 1- to 3-mL self filling,
plastic, disposable syringe.
• Lyophilized and liquid heparin are acceptable
• Once drawn, the blood in syringe must be
mixed thoroughly with heparin
• Other forms available: ammonium, zinc,
electrolyte balanced, and calcium titrated.
• Slow filling of the syringe may be caused by a
mismatch of syringe and needle sizes
• Needle sizes
• Transport time prior to analysis should be
minimal
• Oxygen and carbon dioxide levels in blood kept
at cool room temperature for 20-30 minutes or
less are minimally affected.
• The best practice in avoiding may of preanalytic
error is to analyze the sample as quickly as
possible.
INTERPRETATION OF RESULTS
• Instrument problem: Possible bubble in the
sample chamber or fibrin plug
• Possible sample handling problem: pO2 out of
line with previous results and current inspired
FiO2 levels
Thyroid Gland below 50 nanograms daily the thyroid can not
prodeuce adequate amounts of thyroid
-It consists of 2 lobes (one the either side of
hormones and thus hormone deficiency occurs.
trachea , it is located at the lower part of the
neck just below the larynx/voice box) which is
connected by the ISTHMUS(narrow bond)
Functions of Thyroid Hormones:
-aka: butterfly-shaped gland
-for tissue growth
-by 11 weeks of gestation, the gland begins to
-for mental development
produce measurable amounts of hormones
-for development of CNS
-The thyroid cells are organized into FOLLICLES.
-elevated heat production (when there is an
=Follicles: spheres of thyroid cells---
increased in body temperature thru the use of
Fndamental structural unit of the thyroid
chemical energy for metabolic processes which
gland.surrounding a core of viscous substance
is fueled mainly by fatty acids)
called COLLOID
-control of oxygen consumption
=Colloid: Major component is Thyroglobulin
-it influences carbohydrate and protein
-2 type of cells secreted in the thyroid gland:
metabolism
=FOLLICULAR CELLS (secrtes T3 and T4)
-for energy conservation
=PARAFOLLICULAR CELLS of C cells
(secretes calcitonin)
Major Thyroid Hormones:
-THYROGLOBULIN: a glycoprotein, is the matrix
for thyroid hormone synthesis, it is a from in 1. TRIIODOTHYRONINE (T3)
which hormone is stored in the gland.
-has the most active thyroid hormonal activity
Hormone:
-for diagnosing T3 thyrotoxicosis (Principal
1. Thyroid Hormone: application)
-Follicular cells produce teo iodine-containing -helpful in confirming the diagnosis of
hormones, thyroxine (T4) (tetraiodothyronine) hyperthyroidsim (better indicator of recovery
and triiodothyronine (T3)---Iodine is the most from hyperthyroidism and recognition of
important element in the biosynthesis of recurring of hyperthyroidism)
Thyroid hormone.
-reference value:
-the hypothalamic-pituitary-thyroid axiz (HPTA)
=adult: 60-160ug/dL or 0.9-2.46 nmol/L
is the neuroendocrine system that regulates the
production and secretion of thyroid hormones =Children: 1-14y/o:105- 245 nmol/L or
1.8-3.8 nmol/L
-TH affects the synthesis, degradation, and the
intermediate metabolism of adipose tissue and
other circulating lipids.
2. TETRAIODOTHYRONINE/ THYROXINE (T4)
-Differenet carrier proteins:
-it is the principal secretory product
=TBG: thyroxine binding globulin (70-75%)
-it has the major fraction of organic iodine in the
=TBPA: thyroxine binding prealbumin or circulation (amount of serum T4 is a good
TTR transthyretin (10-25%) indicator for the Thyroid Secretory Rate)
=TBA: thyroxine binding albumin (10%) -It is a prohormone for T3 producton
***Recommended minimum daily intake of -Reference value:
Iodine is 150 micrograms/dL, if Iodine intake is
 = Adult: 5.5-12.5 ug/dL or 71-161nmol/L Secondary Hyperthyroidism

=Neonates/Children: 11.8-22.6ug/dL or -Overstimulation of the thyroid, Over production

152-292 nmol/L of thyroid stimulating hormone

-Due to lesions/injuries in the pituitary gland

DIAGNOSTIC SIGNIFICANCE -Causes:

Clinical Condition TT4 TT3 FT4 TSH =Carcinoma

1⁰ Hypothyroidism ↓ ↓ ↓ ↑ =TSH- secreting tumors

2⁰ Hypothyroidism ↓ ↓ ↓ ↑ =TRH- secreting tumors

1⁰ Hyperthyroidism ↑ ↑ ↑ ↓

2⁰ Hyperthyroidism ↑ ↑ ↑ ↑ Signs and Symptoms of hyperthyroidism

1⁰ Increased TBG ↑ ↑ N N -tachycardia- heart rate is over 100bpm

1⁰ Decreased TBG ↓ ↓ N N -tremors

-weight loss

FT4-used to differentiate drug induced TSH -heat intolerance

elevation and hypothyroidism -emotional lability- rapid changes in mood
TBG- helpful in the diagnosis of patients having -menstrual changes
elevated T3 and T4 levels, no correlation with
other Thyroid function test or not compatible
with the clinical findings Primary Hypothyroidism

-Primarily due to deficiency of elemental iodine

Primary Hyperthyroidism ( decreased T3 and T4, increased TSH)

-Hypermetabolic condition caused by excessive -caused by destruction of thyroid gland

production of thyroid hormones (due to the
presence of functioning parathyroid carcinoma)
-Graves’ disease- Autoimmune disease that leads
to generalized over activity of the thyroid
gland--- most common cause of thyrotoxicosis
-other causes:
=surgical removal of the gland
=use of radioactive iodine for
hyperthyroidism treatment

=characteristics: bulging eyes and pretibula =radiation exposure

myxedema- is the localized lesion of the skin
which results to deposition of hyaluronic acid
and eventually lead to bulging
=drugs (lithium)
-Hashimoto’s Disease (most common cause of
primary hypothyroidism)- Autoimmune disorder
in which the immune system creates antibodies
that damage the thyroid gland (enlargement of
thyroid gland--- Goither)

Secondary Hypothyroidism

-Due to pituitary destruction or pituitary

adenoma (decreased T3, T4, TSH)
2.Calcitonin:
-Produced by th C-cells (parafollicular) of the
thyroid and its production is stimulated by
hypercalcemia
-Lowers plasma Ca+2 level and promotes Ca+2
deposition in bones and urinary excretion of
calcium (opposes the effect of PTH which acts to
increase blood calcium level)
-It is a tumor maker for drtrcting residual
thyroid metastasis on medullary thyroid
carcinoma (MTC)
Parathyroid Glands
-Located at the posterior of the thyroid which
consists of tightly packed secretory cells covered
by thin connective tissue
-smallest endocrine gland in the body
Functions:
1. Primary role: its release is stimulated by
hypocalcemia and increase plasma calcium
levels--- regulates blood calcium, preserve
calcium and phosphate within the normal range
2. It promotes bone resorption
3. It increases renal reabsorption of calcium
4. It stimulates the conversion of inactive
VItamin D to activated Vitamin D3
5. Indirectly stimulates intestinal absorption of
calcium
Diagnostic Significance:
Primary Hyperparathyroidism
-80% of this condition is due to Parathyroid
adenoma
-Most common cause of hypercalcemia
-accompanied with phospahturia
-if it goes undetected, severe demineralization
may occur which causes osteitis fibrosa cystica
Secondary Hyperparathyroidism
-it develops in response to derease serum
calcium
-due to vitamin d deficiency- severe bone disease
-seen in chronic renal failure
Hypoparathyroidism
-due to accidental injury to the PTG-- surgery or
post-surgery causes
-other cause:
= autoimmune destruction
=persistent hypocalcemia
=deficiency of blood calcium causes neurons
and muscle fibers to depolarize and produce
action potentials spontaneously--- experience
twitches, spasms or tetani on their skeletal
muscle
3. Adrenal Glads
-has a pyramid-like shape located above the
kidneys
-its gland sits at top of kidney--- also referred as
suprarenal glands
-Inside the glands: Adrenal medulla and Adrenal
cortex
Structure of Adrenal Glands:
ADRENAL MEDULLA
-comes from neural crest origin and store and
secrtes catecholamines (epinephrine,
norepinephrine, dopamine)
ADRENAL CORTEX
-the outer region of the adrenal glands secreting
the steroid hormone
-major site of steroid hormone production
(Glucocorticoids, Mineralocorticoids, Sex
steroids)
-3 layers of the Adrenal Cortex:
 a. Zona glumerulosa (outermost layer) 10% -occurs as a result of excessive production of
-principal source of mineralocorticoid renin

b. Zona fasiculata (middlemost layer) 75% -increases plassma levels of aldosteron and
-site of glucocorticoid synthesis renin

c. Zona reticularis (innermost layer) 10% -symptoms: hypokalemia

-produces androstenedione and
dehydroepiandoserone--- these are
cosidered as weak androgens 3. Hypoaldosteronism

-due to destruction of the adrenal glands and

deficiency of glucocorticoid
Hormones of Adrenal Glands:
-symptoms: hyperkalemia and metabolic
1. Aldosterone
acidosis
-most potent mineralocorticoid
(electro-regulating hormone)--- regulate water
and electrolyte, maintains blood pressure 2. Cortisol
-it is the main determinant of renal excretion of -principal glucocorticoid
potassium
- influences the metabolism of glucose, protein
-it acts on renal tubular epithelium to increase and fats
retention of Na+ and Cl-, and excretion of K+
-has anti-inflammatory effect and
and H+ (promotes 1:1 exchange of Sodium with
immunosuppressive actions---valuable
Hydrogen or Potassium ion)
therapeutic agent for rheumatoid arthritis or
-the synthesis of this hormone is primarily SLE and Multiple sclerosis
controlled by the renin-angiotenisn-aldosterone
-it stimulates gluconeogenesis in the liver
system (RAAS)--- to increas BP level
resulting in hyperglycemia (anti-insulin effect)
-enzyme neede for synthesis: 28-hydroxysteroid
-negative feedback mechanism controls the
dehydrogenase
release of cortisol (CRH-hypothalamus;
ACTH-anterior pituitary)---only hormone that
inhibits ACTH when plasma level of cortisol is
Diagnostic Significance:
elevated
1. Primary Hyperaldosteronism (Conn’s disease)
-high levels in the morning (8:00- 10:00 AM)
-caused by aldosteron- secreting adrenal and lowest at night (10PM to 12MN)--- circadian
adenoma--- in this condition delivery of sodium rhythm (samples should be drawn at 8:00 AM)
is increased because sodium chloride
reabsorption in the collecting duct via the action
of aldostrone inhibits salt reabsorption in the Diagnostic Significance:
proximal tubules as a result of volume expansion
Hypercotisolism
-associated with increased plasma aldosterone
(Cushing’s Syndrome)
and low plasma renin
-excessive production of cortisol and ACTH,
-symptoms: hypertension, hypokalemia, mild
decreased aldosterone and renin
hypernatremia, and metabolic alkalosis
-also caused by overused of corticosteroids

-S/S: obesity but with thin extremities,

2. Secondary Hyperaldosteronism
hirsutism---excessive growth of hair in women,
hyperglycemia, thinning of the skin, poor wound
healing, hypertension, hypercholesterolemia, b. Norepinephrine (Noradrenaline/ Primary
low WBC(especially lymphocytes) Amine)

-Bufallo hump: -highest concentration is found in the brain

(CNS)

-it acts as a neurotransmitter in both CNS and

the Sympathetic nervous system--- this hormone
also breaks with Epinephrine in responding to
stress, however, it can cause vasoconstriction
which results to High blood pressure.

-MAJOR METABOLITE:
3-methoxy-4-hydroxyphenylglycol (MHPG)-
CSF and urine

Hypocortisolism

-due to destruction of adrenal cortex causes to Diagnostic Significance:

decreased cortisol production, aldosterone
Pheochromocytoma
deficiency, excess ACTH release
-tumor of the adrenala medulla or sympathetic
DISORDER: Addison’s Disease
ganglia
-Due to autoimmune adrenalitis,
-due to overproduction of
Tubercolosis, hemmorrhage, HIV-AIDS
catecholamines---commonly seen in 2 or 3
infections
decades of life
-S/S: hypotension, hyponatremia,
-S/S: hypertension, tachycardia, headache,
hyperkalemia, weight loss, and
tightness of chest, sweating.
hyperpigmentation

Pancreas

-Secretes hormones as an endocrine gland, and

digestive juices (amylase) to the digestive tract
as an exocrine gland.

Endocrine cells: islets of Langerhans

3. Catecholamines -Alpha cells: glucagon

-Produced in Chromaffin cells--- found in -Beta cells: insulin

adrenal medulla
-delta cells: simatostatin
a. Epinephrine (Adrenaline/Secondary amine)
-F cells: pancreatic polypeptide
-it is called the “FLIGHT OR FIGHT HOMONE”
---because it is release during physiologic
factors such as injuries, or in psychological
Hormones:
factors such as stress, anxiety
-it also spikes your blood sugar level by helping 1. Glucagon
convert glycogen to glucose in the liver
-it stimulates the conversion of stored glycogen
MAJOR METABOLITE: VANILLYLMANDELIC (stored in the liver) to glucose, which can be
ACID (VMA)--- major catecholamine metabolite releases into the bloodstream---Glycogenolysis
in urine derived largely from norepinephrine
-it promotes the production of glucose from
amino acid molecules---Gluconeogenesis

-It reduces glucose consumption by the liver so

that as much as glucose as possible can be
secreted into the bloodstream to maintain blood
glucose levels.

***prevent blood glucose levels from dropping

to low

-released during stress and fasting states

2. Insulin

-the primary hormone responsible for the entry

of glucose into the cell

-release is stimulated by hyperglycemia

-it promotes glycogenesis, lipogenesis and

glycolysis, decreases glycogenolysis

*** only hormone that decreases glucose levels

(hypoglycemic agent)---reciprocal relationship
with glucagon

Diagnostic Significance:

DM I DM II

Onset Most common Most common

in children/ with advancing
teens(below 20 age
y/o)

Risk factors Genetic, Genetic,

autoimmune obesity,
sedentary
lifestyle, PCOS,
dyslipidemia,
hypertension

C-peptide levels Decreased or detectable

undetectable

symptomatology Develop Develop

abruptly gradually

medication Insulin Manage diet

absolute- and exercise,
parenteral oral agents
TOXICOLOGY
• is the study of the adverse effects of xenobiotics in Section 1. DRUGS OF ABUSE
humans. • almost all drugs of abuse are basic drugs ( amine
• Xenobiotics are chemicals and drugs that are not derivatives) which
normally found in or contain benzene rings; barbiturates ( acidic drugs)
produced by the body Nature of drug dependence:
4 MAJOR DISCIPLINES: 1. Psychological - is when a person develops an
1. mechanistic uncontrollable “craving”
2. descriptive for a drug.
3. forensic 2. Physiological - the body continually needs to have
4. clinical the drug, a person
experience sickness if drug is discontinued.
Mechanistic toxicology
• elucidates the cellular, molecular, and biochemical Six Categories of Drugs of abuse
effects of toxins 1. Opiates and Narcotic Drugs
• provide a basis for rational therapy design • are capable of analgesia, sedation, and
• to assess the degree of exposure in individuals. anesthesia
Descriptive toxicology • they are derived chemically from opium poppy
• uses the results from animal experiments to predict Naturally occuring opiates: opium, morphine,
what level of exposure will cause harm in humans codeine
Forensic toxicology Chemically modified opiates: heroin,
• concerned with the medicolegal consequences of hedromorphone, and oxycodone ( percodan)
toxin exposure.
Clinical toxicology A. Morphine
• is the study of interrelationships between toxin • is a metabolite of heroin, a powerful analgesic, for the
exposure and disease states. treatment of Acute Congestive Heart Failure
B. Opium
ROUTES OF EXPOSURE • psychologically addictive drugs; withdrawal causes
1. Ingestion- is most often observed in the clinical severe physiological symptoms
setting C. Codeine
2. inhalation • second most abundant component of opium, used as
3. Transdermal a strong painkiller and cough suppressant
Toxicity rating Lethal oral dose in Average adult TOXIC EFFECTS: respiratory acidosis, myoglobinuria,
Super toxic <5 mg/kg cardiopulmonary failure and pupillary constriction (
Extremely toxic 5-50 mg/kg pin-point pupils)
Very toxic 50-500 mg/kg
Moderately toxic 0.5-5 g/kg 2. Stimulants
Slightly toxic 5-15 g/kg • are taken to make one feel more energetic, strong, or
Practically >15 g/kg awake
nontoxic A. Amphetamine- used to treat ADHD and narcolepsy
B. Methamphetamine is the drug most commonly
Terminologies: produced in
1. Acute toxicity- single, short-term exposure to a clandestine labs. Also known as meth, blue, ice, and
substance crystal, white
2. Chronic toxicity- repeated exposure for extended powder
period of time. • originally used as nasal decongestant and bronchial
3. TD50- is the dose that would be predicted to produce inhaler
a toxic response in 50% of the population. • 3,4 methylenedioxymethamphetamine ( MDMA/
4. LD50- is the dose that would predict death in 50% of ecstasy): a derivative
the population of methamphetamine
5. ED 50- is the dose that would be predicted to be C. Cocaine
effective or have a therapeutic benefit in 50% of the • very powerful stimulant; enormously psychologically
population. addicting
• Cocaine hydrochloride is usually inhaled through the
nose
• used as a local anesthetic for nasopharyngeal surgery
• it crosses the placenta and mammary glands
• for single use, it can be detected in urine up to 3 days;
up to 20 days for chronic users
• URINE METABOLITE: Benzoylecgonine ( sensitive and
specific indicator)
• TOXIC EFFECTS: hypertension, arrythmias, seizures,
and MI
3. HALLUCINOGENS
Physiolgically active ingredients: cannabinoids
Most common Naturally occurring cannabinoids:
marijuana and hashish
A. MARIJUANA
Most active cannabinoid: THC ( tetrahydrocannabinol)
Principal psychoactive ingedient: delta-9-
tetrahydrocannabinol
Urinary metabolite: 11-nor-
deltatetrahydrocannabinol/ 11-hydroxydelta 9- THC
( THC-COOH)
• after a single use, TCH-COOH can be detected in urine
for 3-5 days; up
to 4 weeks for chronic users
B.HASHISH
• more potent form of marijuana made from the
flowering tops of the
plant
C. LSD- Lysergide ( Lysergic acid diethylamide)
• is an extremely potent hallucinogen with normal dose
of 30-50 mg, this
causes visual hallucinations, brilliant colors and the
perception that one
is wise.
• Most adverse reaction: Panic reaction - “Bad trip”
• Toxic effects: blurred or “undulating” vision and
synesthesia
4. DEPRESSANTS, HYPNOTICS, AND TRANQUILIZERS
A. ALCOHOL ( DEPRESSANT)- most abused substance
B. BARBITURATES ( sedative hypnotic) - physiologically
active
depressants, resulting in a physical & mental state
similar to alcoholinduced intoxication
• are condensation products of urea and malonic acid
• they increase gamma aminonutyric acid ( GABA)
activity in the brain
Commonly abused barbiturates: secobarbital,
pentobarbital, phenobarbital, thiopental
Toxic effects: Cheyne-Stokes respiration, depression,
cyanosis, areflexia, stupor, coma
C. BENZODIAPINES- are used for treatment of cocaine
addiction
a. Valium/Diazepam- a tranquilizer drug designed to
relieve anxiety
b. Rohypnol- “ roofies”
• It is used in the short-term treatment of insomnia, as
a premedication in surgical procedures and for inducing
anesthesia.
• “ date-rape drug”
5. CLUB DRUGS
A. MDMA ( 3-4 methylenedioxymethamphetamine)
• love drug/ ecstasy
• increases brain chemicals: dopamine, norepinephrine,
serotonin
B. GHB( gamma hydroxybutyrate)- used for their
hypnotic or depressant effects.
• used as general anesthetic and as a treatment for
cataplexy, narcolepsy,
and alcoholism.
C. Ketamine - anesthetic and animal tranquilizer; causes
anterograde
Amnesia
6. ATHLETIC PERFORMANCE ENHANCERS
A. anabolic steroids
• promotes cell growth resulting in growth of muscle
tissue and
sometimes bone size and strength
THERAPEUTIC DRUG MONITORING
 It involves the analysis, assessment and
evaluation of circulating concentrations of drugs
in serum, plasma or whole blood.
Purpose: Ensures that a given drug produces maximal
therapeutic benefit and minimal side effects, to achieve
a constant serum level of drug that will be therapeutic
 Quantitative procedure – with narrow
therapeutic index
 Factors: age, gender, genetics, diet
  Mixed Function Oxidase (MFO) system –
biochemical pathway responsible for the
greatest portion of drug metabolism.
Routes of administration
- Intravenous – associated with 100%
bioavailability
- Intramuscular
- Subcutaneous
- Inhalation
- suppository
- transcutaneous
- Oral – most common and least invasive
(bioavailability = 70%)
Indications for TDM:
1. Adverse effects of overdosing and under-dosing
2. The margin of safety is narrow.
3. There is a poor relationship between the dose of drug
and circulating concentrations but a good correlation
between circulating concentrations and therapeutic and
toxic effects.
4. There is a change in the patient’s physiologic state
that may unpredictably affect circulating drug
concentrations.
5. An unfavourable drug interaction occurs or is
anticipated.
6. Monitoring patient compliance
5 pharmacological parameters that determine serum
drug concentration
1. Liberation – release of drugs
2. Absorption – tablets and capsules (requires
dissolution before being absorbed) liquid
are rapidly absorbed
 Most drugs are absorbed by passive
diffusion
3. Distribution – delivery of drug to different
tissues
4. Metabolism – chemical modification of the
drug by the cells
5. Excretion – drugs and its metabolise are
excreted to the body
Terminologies
 Bioavailable fraction – is the fraction of the dose
that reaches the blood
 Half-life – the time required to reduce a drug
level to half of its initial value
 Peak concentration – the highest concentration
of a drug obtained in the dosing interval
 Drawn 1 hour after an orally
administered dose
 Accurate timing of specimen collection
is the single most important factor in
TDM
 Trough concentration – is the lowest
concentration of a drug obtained in the dosing
interval
 Sample are drawn right before the next
dose is given
 Drugs that are absorbed at slower rate
may require several hours before drug
concentration can be evaluated
1. Cardioactive drugs
- used to treat congestive heart failure and
- Net effect: slow down electrical conduction
Classifications:
- Class I – rapid sodium channel blockers
(Quinidine Procainamide Lidocaine Phenytoin)
- Class II – beta adrenergic blockers (Propranolol)
- Class III – potassium channel blockers
(Amiodarone)
- Class IV – calcium channel blockers (Verapamil)
Cardiotrioics
1. Lidocaine/xylocaine
- Administered by continuous IV infusion after a
loading dose
- Can’t be administered orally due to almost
complete hepatic removal of the absorbed drug
- It is used to correct ventricular arrhythmia for
treatment of acute myocardial infraction
- It is a local anaesthetic
- Toxic effects: convulsions, coma, respiratory
depression, bradycardia, hypotension
- Decreases blood pressure
2. Quinidine
- A naturally occurring drug for the treatment of
supraventricular and ventricular arrhythmia
 - Common formulation: quinidine sulfate and
quinidine gluconate
- Administered orally
- Toxic effects: Cinchonism- vertigo, tinnitus,
headache, visual disturbances and
disorientation
3. Procainamide
- for supraventricular or ventricular arrhythmias
- Metabolite : n-acetylprocainamide
- Toxic effects: Reversible lupus-like syndrome w/
elevated ANA titers, urticaria, rash,
agranulocytosis and nephrotic syndrome
4. Propranolol
- Antagonizes effects of epinephrine on the heart,
arteries and arterioles of skeletal muscles and
on the bronchus - causes vasodilation
- used for treatment of hypertension and angina
- supresses the conversion of T4 and T3
- toxic effects: bradycardia, arterial insufficiency,
platelet disorder, pharyngitis
5. Amiodarone/cordarone
- for life-threatening ventricular arrhythmias
- It is a iodine containing drug which can cause
hyperthyroidism or hypothyroidism
- Toxic effects: bradycardia, hepatitis,
photodermatitis, and thyroid dysfuction
6. Verapamil
- angina, hypertension, supraventricular
arrhythmias
- toxic effects: nephrotoxicity and ototoxicity
Digital glycosides – for heart failure
1. Digoxin
- Inhibits membrane Na+ -K + -ATPase - -
Decreases K+ and Mg+ and increases Ca+
(cardiac contractility- inotropic effect)
- Rapid onset of action : 1-2 h after oral
administration
- Peak serum level: 8 hours after oral dose
- Toxic effects: nausea, vomiting, visual
disturbances, premature ventricular
contractions and atrioventricular node blockage.
2. Digitoxin
- Active metabolite: Digoxin
- Slower onset of action (1-4 hours oral)
Antibiotics
1. Aminoglycosides
- Examples: Gentamicin, tobramycin, amikacin
and kanamycin
- Treatment of gram (-) bacterial infections
- Administered IM or IV
- It requires trough and peak measurements
- Elimination: renal filtration
- Toxic effects: nephrotoxicity and ototoxicity
2. Vancomycin
- Effective against gram (+) cocci & bacilli
- Administered by IV infusion
- Toxic side effects occur in the therapeutic range
(5 – 10 μg/mL)
- Trough levels are monitored
- Toxic effects: “red-man syndrome”,
nephrotoxicity and ototoxicity
- Elimination: renal filtration and excretion
Anti-seizure drugs
1. Phenobarbital
- Slow-acting barbiturate that controls several
types of seizures
- Used for treating withdrawal symptoms in
infants-mother who are addicted to opiate or
barbiturate
- Used to treat cases of congenital
hyperbilirubinemia
- -Only trough levels are evaluated unless there is
toxicity
- Toxic effects: Nystagmus, ataxia, stupor,
respiratory depression, hypotension and coma
2. Phenytoin (Dilantin)
- It controls seizures (tonic-clonic, simple partial
seizures), a short-term prophylactic agent in
brain injury
- It decreases sodium and calcium influx into
hyperexcitable neurons
- IV administered
- Toxicity is seen at the level of the therapeutic
range
- Elimination: hepatic pathway( zero-order
kinetics)
- Major toxicity: initiation of seizures Other
- Toxic effects: hirsutism, gingival hyperplasia, Vit.
D & folate deficiency
3. Valproic acid (Depakene)
- used for treatment of petit mal and absence
seizure
- orally
- therapeutic level: 50-100 ug/mL
- elimination: hepatic metabolism
- Toxic level: > 120 µg/mL - nausea,
lethargy and weight gain > 200 µg/mL -
pancreatitis, hallucinations, hyperammonemia
(hepatic dysfunction)
4. Carbamazepine (Tegretol)
- used for the treatment of various seizure
disorders and trigeminal neuralgia (tic
douloureux)
- chemically related to imipramine (TCA)
 - elimination: hepatic elimination
- toxic effects: hematologic dyscrasias, aplastic
anemia, irregular pulse and ataxia
5. Primidone
- - for generalized tonic clonic, simple partial and
complex partial seizures
- Metabolites: Phenobarbital and
phenylethylmalonamide
6. Ethosuximide (Zerontonin)
- for treatment of petit mal (absence) seizures
- toxic effects: GI disturbances, ataxia, SLE,
aplastic anaemia and pancytopenia
ANTI-ASTHMA DRUGS/bronchodilator
1. Theophylline
- It belongs to the methylated xanthine class
- For the relaxation of bronchial smooth muscle
- Drug for primary apnea of prematurity
- Its action is inhibitory to the release of
histamine and other proinflamatory agents
- Its crosses the placenta
- The best predicator of toxicity is the blood level
of the drug and not the early signs or symptoms
of toxicity
- Elimination: renal filtration and hepatic
metabolism
- Toxic effects: Gi bleeding, seizures, tachycardia
and syncope
ANTI-INFLAMMATORY DRUGS
1. Corticosteroids
- Block the cyclo-oxygenase pathway
- Anti-inflammatory
- Toxicity: Fluid retention, weight gain,
osteoporosis, gastrointestinal bleeding and
mental changes
NSAIDS/ nonsteroidal anti-inflammatory drugs
1. Acetylsalicylic acid (Aspirin)
- Commonly used analgesic, antipyretic and
antiinflammatory drug
- decreases thromboxane and prostaglandin
formation through inhibition of cyclooxygenase
- Direct stimulator of the respiratory system and
an inhibitor of the Kreb’s cycle
- Acute aspirin intoxication is a common cause of
fatal drug poisoning in children
- Toxic effect: mixed acid-base balance
disturbance (metabolic acidosis and respiratory
alkalosis), hypoglycaemia, reye’s syndrome
2. Acetaminophen /Paracetamol
- Inhibitor of prostaglandin metabolism
- It is commonly used as an analgesic and
antipyretic drug
- Overdose of this drug leads to hepatoxicity
- Metabolite: glucoronide and sulfate conjugates
- Toxic effects: cyanosis due to
methemoglobinemia, CNS depression and
seizures
IMMUNOSUPPRESSIVES
1. Cyclosporine
- It inhibits the cellular immune response by
blocking production of interleukin 2
- Used for suppression of acute graft-versus-host
disease (GVHD)
- Drug of choice for maintenance of kidney, liver,
heart and heart-lung allografts
- It has a marked affinity with RBC; RBC
cyclosporine is temperature dependent
2. Tacrolimus(prograf/FK-506)
- Currently used in transplant surgery to prevent
organ rejection
- 100x more power full than Cyclosporine
- Elevated levels are observed in cholestasis
- Elimination: hepatic metabolism
- Toxic effect: thrombus formation,
nephrotoxicity and neurotoxicity
3. Rapamycin (Sirolimus)
- Similar to tacrolimus
- major side effects are lipid abnormalities and
thrombocytopenia
4. Mycophenolate mofetil
- Rapidly converted in the liver into its active
form, mycophenolic acid (MPA)
- A lymphocyte proliferation inhibitor
- It decreases renal allograft rejection
5. Leflunamide (LFM)
- Inhibits lymphocyte proliferation
- for treatment of rheumatoid arthritis
Psychoactive drugs
1. Lithium (as Lithium citrate or Lithium carbonate)
- Orally
- used for the treatment of manic depression
- the drug of choice for prevention of chronic
cluster headache
- it inhibits the effect of ADH on the kidney
- *1.2 – 2.0 mmol/L – apathy, lethargy, speech
difficulties
- * > 2.0 mmol/L – seizures, muscle rigidity and
coma Others: Renal toxicity & hypothyroidism
2. TRICYCLIC ANTIDEPRESSANTS
- Examples:imipramine, amitriptyline, doxepin,
desipramine and nortriptyline
- Orally
- Block reuptake of adrenergic and dopaminergic
neurotransmitters
- Used for the treatment of depression, insomnia,
extreme apathy and loss of libido
 - Major metabolite: desipramine
- Toxic effect: drowsiness, blurred vision,
memory loss, seizue, cardiac arrhythmia,
parkinsonian syndrome, and unconsciousness
3. Fluoxetine (Prozac)
- Blocks the re-uptake of serotonin in central
serotonergic pathways
- Used to treat obsessive- compulsive disorder
- Side effects: attempted suicide, decreased
libido and sexual function
CHEMOTHERAPEUTIC AGENTS
1. Methotrexate
- - Inhibits DNA synthesis by blocking
dihydrofolate reductase
- used for the treatment of Psoriasis, Refractory
rheumatoid arthritis and Malignant neoplastic
diseases
- toxic effect: Hematologic effects (leucopenia,
thrombocytopenia), GI effects (ulceration),
cirrhosis
2. Busulfan
- An alkylating agent used for the treatment of
leukemias and lymphomas prior to BM
transplantation
- Depresses granulocyte formation; used in the
treatment of myelocytic leukemias
- Over dosage may cause hepatic occlusive
disease
Endocrine system
• Is a network of ductless glands that secrete
hormones directly into the blood
• It is regulated by means of control of hormone
synthesis rather than degradation

Hormones

• Are chemical signals produced by specialized

cells secreted into the blood stream and carried
to a target tissue
• They are regulated by the metabolic activity
either positive or negative feedback mechanism

Major functions:

• To maintain the constancy of chemical

composition of the ECF and ICF
CLASSIFICATION OF HORMONES ACCORDING TO
• Controls metabolism
COMPOSITION OR STRUCTURE:
• Growth
• Fertility A. PEPTIDES AND PROTEINS
• Response to stress
• Are synthesized and stored within the cell in the
Feedback mechanism: form of secretory granules and are cleaved as
needed
1. Positive Feedback mechanism
• They cannot cross the cell membrane due to
• A system in which an increased in the product their large molecular size
results to elevation of the activity of the system • They are water soluble and not bound to carrier
and the production rate protein

1. Glycoproteins : FSH, HCG, TSH, erythropoietin

2. Polypeptides: ACTH, ADH, GH, angiotensin,

calcitonin, cholecystokinin, gastrin, glycagon,
insulin, melanocyte- stimulating hormone, oxytocin,
PTH, prolactin, somatostatin
2. Negative feedback system
B. STEROIDS
• Is a system in which an increased in the product
results to decreased activity of the system and • They are produced by the adrenal glands,
the production rate ovaries, testes and placenta
• They are water insoluble and circulate
bound to a carrier protein
• Examples: aldosterone, cortisol, estradiol,
progesterone, testosterone, and activated
vitamin D3

C. AMINES

• They are derived from an amino acid and they

are intermediary between steroid and protein
hormones
 • Examples: epinephrine, norepinephrine, • Elevated fatty acids
triiodothyronine, and thyroxine
INCREASED GH:
ENDOCIRNE GLANDS
• Acromegaly/ gigantism
1. Pineal Gland • Chronic malnutrition
• Renal diseases
• Located at the mid brain
• Cirrhosis
• Secretes melatonin that decreases melanin of
• Sepsis
the skin
• Secretions are controlled by nerve stimuli DECREASED GH:
2. Pituitary Gland • Hyperglycemia
• Obesity
• “master gland”
• Hypothyroidism
• Located in a small cavity in the sphenoid bone
• Dwarfism
of the skull called the turcica or Turkish saddle
ACROMEGALY
A. Anterior Pituitary Gland (adenohypophysis)
• Results from pathologic autonomous GH excess
• It is the “true endocrine gland”
caused by a pituitary tumor
• The hormones secreted by this anterior lobe are
• Results in increased width of bone rather than
either peptides or glycoproteins
length and usually affects the hand, feet and
• It regulates the release and production of
jaw
hormones such as prolactin, GH, gonadotropins
• It may also result to generalized organomegaly
(FSH and LH), TSH and ACTH
and coarsening of the facial features with
HORMONES SECRETE BY THE ANTERIOR PITUITARY hyperglycemia
GLAND
DWARFISM
1. Growth Hormone (Somatotropin)
• Congenital or acquired, idiopathic-damage to
• Is the most abundant of all pituitary hormones the pituitary gland or hypothalamus deficiency
• Structurally related to prolactin and human of other pituitary hormones
placental lactogen • IN CHILDREN: familial or may be due to tumors
• Its release is controlled by GH-RH; secretion is (craniopharyngiomas)
inhibited by SOMATOSTATIN • IN ADULT: it is result of structural or functional
• Its overall metabolic effect is to metabolize fat abnormalities of the pituitary
stores while conserving glucose
DIAGNIOSTIC TEST:
• Major stimulus: deep sleep
1. for GH Deficiency
Physiologic stimuli
a) Screening test: physical activity test (exercise
• Stress
test)
• Fasting
b) Confirmatory test: insulin Tolerance Test- Gold
• High protein diet
Standard
Pharmacological stimuli • Interpretation: failure of GH to rise
greater than 5 ng/ml (adults) and
• Sex steroids greater than 10 ng/ml (child) is
• Apomorphine confirmed GH deficient
• Levodopa
2. For Acromegaly
GH Suppressors:

• Glucocorticoids
 a) Screening test: Somatomedin C or Insulin- Like FEMALES
Growth Factor 1 (IGF-1)
• aids in the growth and maturation of ovarian
b) Confirmatory test: Glucose Suppression Test
follicles
(OGTT-75g glucose)
• promotes secretion of estrogen (promotes
2. THYROID STIMULATING HORMONE development of breast, uterus and vagina) by
maturing follicles (in the presence of LH)
• Aka Thyrotropin
• Elevated FSH in females is a diagnosis of a
• It is composed of 2 mono-covalently linked to
premature menopause
alpha and beta subunits
LUTEINIZING HORMONES
Functions:
plays an important role in sexual development or
• It is the main stimulus for the uptake of iodide
functioning
by thyroid gland
• Promotes release of stored thyroid hormone MALES

DIAGNOSTIC METHODS FOR TSH • responsible for production of testosterone by

Leydig cells of the testes
• IRMA (immunoradiometric assay)
• Causes the testes to produce testosterone that
o Hypothyroidism- TSH is elevated
is important for the production of sperms
• LATS (Long Acting Thyroid Stimulating
Substance) FEMALES
o Detectable in the serum of thyrotoxic
• necessary for ovulation and the final follicular
patients which imitates the biologic
growth
action of TSH
• cause release of ova from ovarian follicles
3. Gonadotropins • LH in women helps control the menstrual cycle
and it also triggers of an egg from ovary.
• secreted by gonadotropic cells and control the
• Increased of LH and FSH after menopausal is
functional activity of gonads
due to the lack of estrogen
GONADS (produces gametes)
DIAGNOSTIC METHODS FOR GONADOTROPINS
• For males: testes
• Commercial RIA (serum, plasma, urine samples)
o LH and FSH is regulated by testosterone
• Because of the episodic Circadian Rhythm of
and inhibin
Gonadotropins the clinical evaluation requires
• For females: ovary
determinations in: pooled blood samples,
o LH and FSH is regulated by estrogen and
multiple serial blood samples and Times sample
inhibin
of urine.
LH and FSH are present in both men and women at all
4. Prolactin or Leuteotropin
ages. These are important in diagnosing fertility and
menstrual cycle disorders in women • a pituitary lactogenic hormone, a stress
hormone
FOLLICLE STIMULATING HORMONE
• same amino acid sequence with GH
MALES • MAJOR INHIBITOR: Dopamine
• functions in the initiation and maintenance of
• Stimulates testicular growth
lactation
• aids in spermatogenesis
• highest serum level (during sleep:4am-8am,
• Production of ABP(androgen binding protein)
8pm-10pm), lowest at 10am to 12nn-- affected
by the Stercoli cells
by circadian rhythm
• INCREASED in conditions such as: pituitary
adenoma, infertility, amenorrhea, galactorrhea,
 acromegaly, renal failure, polycystic ovary
syndrome, cirrhosis, primary and secondary
hypothyroidism
• effect of Prolactin in males is less understood
and may be a cause of deficiency in male sex
hormone
• Diagnostic method: RIA
5. Adrenocorticotropic Hormone
• is a single-chain peptide without disulfide bonds
• acts primary on the adrenal cortex stimulating
its growth and the secretion of corticosteroids
• controls the secretion of hormones from the
adrenal cortex
• Regulated by corticotropin-releasing hormone
from the hypothalamus
• stress can also trigger its release
CLINICAL IMPORTANT HORMONES OF THE POSTERIOR
PITUITARY GLAND
1. Antidiuretic Hormone(ADH)/ Arginine
Vasopressin(AVP)- acts on the distal convoluted tubules
and the tubules in the kidney
Functions:
• major function: to maintain osmotic
homeostasis by regulating water balance (it
decreases production of urine by reabsorption
of water by the renal tubules which maintain
water homeostasis)
• it increases blood pressure (decrease in blood
volume/blood pressure will likewise stimulate
the production of ADH)
• it is a potent pessor agent and effects blood
clotting (by promoting factor 7 release from
hepatocytes and factor 8 (Vonweilbrand’s
factor) released from endothelium)
DIAGNOSTIC SIGNIFICANCE OF ADH
1. Hypothalamic Diabetes Insipidus
• aka Neurogenic, Central or Cranial, Diabetes
insipidus
• a deficiency of ADH with normal ADH receptor
(failure of pituitary gland to secrete ADH---
there is a large volume of urine secreted per
day 2 to 3 L/day)
• Associated with neoplastic disease, surgery,
head trauma, hypoxia, granulomatous disease,
infections and autoimmune diseases
2. Nephrogenic Diabetes Insipidus
• characterized by having a normal ADH but
abnormal ADH receptor
• either congenital or acquired
• it is due to failure of the kidneys to respond to
normal or elevated ADH levels
3. Psychogenic or primary Polydypsia
• caused by Chronic and excessive intake of water
suppresses AVP secretion
• hypothalamic disease affecting the thirst-center
of the brain causes hypotonic polyuria---
excretion of large volume of urine exceeds
50mg/kg per hour in older children and adults,
urine with an osmolality lesser than 300mos/kg
5. SIADH (Syndrome of Inappropriate Antidiuretic
Hormone)
• Plasma AVP concentrations are increased
without known stimuli
• characterized by decreased urine volume, low
plasma osmolality, and normal or elevated
sodium levels or other electrolytes
• Result
o malignancy
o acute and chronic disease of the CNS
o Side effects of drugs
6. Oxytocin
• during childbirth: causes contraction of uterine
muscles (FERGUSSON REFLEX -neuroendocrine
reflex, fetal distention of the cervix stimulates a
series of neuroendocrine response leads to
production of oxytocin) and in milk-letdown by
forcing milk into ducts from milk glands
• plays a role in the homeostasis as a placental
site following delivery
• Synthetic preparation: to increase weak uterine
contractions during labor and to aid lactation
Thyroid Gland (thyroid Function test : TSH)

Describe completely the thyroid stimulating hormone

- TSH is a glycoprotein consisting of 2 monovalently linked alpha and beta sub units
- Alpha sub units – LH and FSH and hCG
- It is the beta subunit that carries specific information to the bindings receptors for expression of
hormonal activities
- The alpha subunit has the same amono acid sequences as LH, FSH and human chorionic
gonadotropin (hCG)
- TSH controls thyroid cell growth and hormone production by binding to a specific TSH receptor
- TSH binding activates both the cyclic AMP and the phosphoinositol pathways for signal
transduction

The major actions of TSH include the following

A. Changes in thy roid cell morphology

- TSH rapidly induces pseudopods at the follicular cell-colloid border, accelerating thyroglobulin
resorption. Colloid content is diminished as intracellular colloid droplets are formed and
lysosome formation is stimulated, increasing thyroglobulin hydrolysis and thyroid hormone
release.

B. Cell growth Individual thyroid cells increase in size; vascularity is increased, and over a period of time,
thyroid enlargement, or goiter develops

C. Iodine metabolism – TSH stimulates all phases of iodide metabolism, from increased iodide uptake
and transport to increased iodide uptake and transport to increased secretion of thyroid hormones and
thyroglobulin itself.

- TSH stimulates the synthesis and secretion of the two thyroid hormones, Triadothryronine (T3) and
thyroxine (T4)

- Thyrotropin- releasing hormone (TRH) from the hypothalamus controls TSH secretion

Apart from ELISA, describe other methods for determining TSH level in blood
- RIAs, a small amount of a TSH tracer, to which a radioactive molecule has been linked.

- Competes for binding to first antibody (eg. a rabbit antihuman TSH polyclonal antibody). Then
antibody bound TSH, both in the sample and the tracer, is separated from the free tracer in the
supernatant using one of several techniques: a second antibody directed against first (eg, goat
antirabbit immunoglobulin antibody), polyethylene glycol, or staphylococcal protein A. RIAs, the
concentration of TSH in the sample is inversely proportionate to tracer activity. In general, TSH
RIAs are less sensitive and less widely employed than IMAs.
- Third-generation TSH chemiluminometric assays, with detection limits of 0.01 mU/L are less
likely to give false-negative results and can more accurately distinguish between euthyroidism
and hyperthyroidism
Differentiate primary hypothyroidism from secondary hypothyroidism. What are the clinical
manifestations of Hypothyroidism

- Hypothyroidism – defined as a low free t4 level with a normal or high TSH, hypothyroidism is a
clinical syndrome resulting from a deficiency slowing down of metabolic processes.

Primary– thyroid gland dysfunction

Secondary – Pituitary dysfunction (anterior pituitary gland – stimulates TSH (T3 & T4)

Tertiary – Hypothalamus dysfunction (Thyroid releasing hormone)

Condition
Primary - Chronic lymphocyte thyroiditis
(Hashimoto’s thyroiditis)
- Treatment for toxic goiter –
subtotal
- Thyroidectomy or radioactive
iodine
- excessive iodine intake
- subacute thyroiditis
Secondary Hypopituitarism
Tertiary Hypothalamic dysfunction
Comments
- TPOAb or TgAb positive in 80-
90% of cases
- History and physical exam
(neck star) are key to diagnosis
- History and urinary iodine
measurement useful usually
transient
Cased by adenoma radiation
therapy, or destruction of
pituitary
Rare

TSH T3 T4
PRIMARY INCREASED DECREASED DECREASED
SECONDARY DECREASED DECREASED DECREASED

Clinical manifestations of hypothryroidism

- Hyponatremia – occurs due to inappropriate levels of ADH

- Myopathy and elevated levels of creatinine kinase
- Anemia as a result of decreased demand for oxygen carrying capacity
- Hyperlipidemia most notably when the TSH is greater than 10mU/L

What is LATS? What is the clinical significance of this substance?

- Long- acting thyroid stimulator (LATS), distinct from pituitary thyrotropin (TSH), is found in the
serum of some patients with graves disease
- High leels of LATS are frequent associated with pretibial myxedemia but the relation of LATS to
the opthalmopathy of graves disease is less clear
- Although serum LATS level correlate with several parameters of thyroid activity in thyrotoxicosis
the role of this abnormal stimulator in the pathogenesis of graves disease remains uncertain
 - Demonstration that LATS is an immunoglobulin G (IgG) and evidence that the distribution of
thyroid0stimulating activity in the polypeptide chains of the IgG parallels antigen-binding activity
in known antibodies has led to speculation that LATS is an antibody to thyroid antigen(s)

Describe in detail how T3 and rT3 are formed from the deiodination of thyroixine

- Thyroid cells are organized into follicles

- Thyroid follicles (capillary – entry of idodine/ individual follicular cells/ apical membrane/
basolateral membrane – entry of nutrients inside the thyroid follicles)
- Follicles are spheres of thyroid cells surrounding a core of viscous substance called colloid

PRODUCTION: *Iodide form the diet reabsorbed from the GIT will travel through the bloodstream and
will reach the thyroid follicles

*the follicular cell take up the iodie through the basolateral membrane using the sodium iodide
symporter. This is an example of secondary active transport since it uses a sodium gradient to pump the
iodide ions inside the cell. Iodide is now then oxidized via the enzyme thyroperoxidase into iodine
thyroglobulin(backbone of T3 and T4) on the other hand is produced by the follicular cells into the
colloid.

*iodine will bind to tyrosine residues on the thyroglobulin. Each tyrosine can bind 1 iodine ion to form
T1, or 2 iodine ions to form T2

*The joining of two T2 molecules will form T4(thyroxine/tetraiodothronine. The joining of T1 molecule
and a T2 molecule will form T3 or triiodothyronine. Remember that these T3 and T4 are still attached to
a thyroglobulin backbone and can be stored inside the follicles. When the body will already need it. It
will now form a vesicle and will combine to lysosome and undergoes endocytosis. This process is needed
to break down the thyroglobulin backbone, the T4 is released into the blood stream and will need a
carrier protein called thyroxine binding globulin

Describe other methods which are employed for the measurement of T3 and T4 in blood

- T3 uptake (T3-UP) test is a classical method of adjusting a total T4 measurement of alterations in

binding problem
- A T3-UP result is a relative measurement of the unoccupied binding sites of all circulating
proteins, It was originally performed by saturating available binding sites with radiolabeled T3,
then measuring the unbound T3 by absorbing it onto a resin (hence the term T3 resin uptake)

Low Free T4 Normal Free T4 High Free T4

Low TSH Secondary Subclinical Hyperthyroidism
hypothyroidism hyperthyroidism
Severe nonthyroidal Nonthyroidal illness
illness
Normal TSK Secondary Normal Artifact
hypothyroidism Pituitary
Severe nonthyroidal hyperthyroidism
illness Laboratory draw
within 6 hours of
thyroxine dose
High TSH Primary Subclinical Test artifact
hypothyroidism hypothyroidism Pituitary
hyperthyroidism
Thyroid hormone
resistance
CREATINE KINASE
CREATINE KINASE
• MW: 82,000
• in muscle cells: involved in
the storage of high energy
creatine phosphate
TISSUE SOURCE
•Greatest in striated muscle,
brain tissue & heart tissue
•Smaller quantities: bladder,
placenta, GIT, Thyroid, uterus,
kidney, lung, prostate, spleen &
pancreas
STRUCTURE
•Dimer w/ 2 sub-units: B (brain) & M (muscle)
•Each sub-unit w/ a MW of ~ 40,000
•Three isoenzymes:
CK – BB (brain type) CK1
CK – MB (hybrid type) CK2
CK – MM (muscle type) CK3
•All three isoenzymes are found in the cell
cytosol
•CK1 : Brain, prostate, gut, lung,
bladder, uterus, placenta & thyroid
•CK2 : present in varying degrees in
heart muscle (25 – 46% of CK activity)
: minor degree in skeletal muscle
•CK3 : predominates in skeletal &
cardiac muscle
MACROMOLECULAR FORMS

1) Macro CK Type1
-CK1 associated with IgG or
-CK3 w/ IgA
2) Macro CK Type 2
- Oligomeric CK-Mt
Diagnostic Significance

Pronounced Elevation (5 Mild or Moderate

or more times normal) Elevations (2 to 4 time
normal)
-Duchenne’s muscular -Severe exercise, trauma,
dystrophy surgical procedure
-polymyositis -dilirium tremens, alcoholic
-Dermatomyositis myopathy
-Myocardial Infarct -pulmonary infarction
-hypothyroidism
11 July 2020 | 42
CK ISOENZYMES-Tissue localization and sources of
elevation
ISOENZYME TISSUE CONDITION

CK-MM Heart Myocardial Infarction

Skeletal Muscle Skeletal Muscle Disorder

Muscular dystrophy

Polymyositis

hypothyroidism

malginant hyperthermia

physical activity, IM injection

CK ISOENZYMES-Tissue localization and sources of
elevation
ISOENZYME TISSUE CONDITION

CK-MB Heart Myocardial Infarction, Myocardial

Injury
Skeletal Muscle Ischemia, Angina

Inflammatory heart dse, Cardiac

surgery
Duchenne type muscular
dystrophy
polymyositis, Malignant
hyperthermia
Reye's Syndrome

Rocky Mountain Spotted fever,

Carbon monoxide poisoning
•DISEASES of the HEART

-CK level: sensitive indicator of AMI

(Total CK & CK-2)
-CK-MB levels begin to rise w/in 4 – 8
hrs., peak at 12 – 24 hrs. & return to
normal levels w/in 48 – 72 hrs.
-Elevation of Total CK: Cardiac trauma ff.
heart surgery (including transplantation)
CK ISOENZYMES-Tissue localization and sources of
elevation
ISOENZYME TISSUE CONDITION

CK-BB Brain CNS shock

Bladder Anoxic encephalopathy

Lung Cerebrovascular accident, seizure

Prostate Placental or uterine trauma

Uterus Carcinoma

Colon Reye's syndrome

Stomach Carbon monoxide poisoning

Thyroid Malignant hyperthermia
Acute and chronic renal failure
 METHODS of DETERMINATION

1. TANZER-GILBARG ASSAY
FORWARD REACTION: (Opt. pH: 9.0, 340 nm)
CK Creatine-PO4+ADP
Creatine + ATP

PK
ADP + PEP Pyruvate + ATP
 LDH
Pyruvate +NADH + H Lactate+ NAD
2. Method by Oliver – Rosalki:
utilizes the reverse reaction
•Most commonly performed
method
•The rate of NADPH formation is
a measure of the CK activity
• REVERSE REACTION: (Opt. pH: 6.8)
CK
Creatine PO4 +ADP Creatine + ATP

HK
ATP +Glucose ADP+ G-6-PO4
 G6PD
Glucose-6-PO4 + NADP
6-Phosphogluconate + NADPH + H
NOTES TO REMEMBER
1. Hemolysis may elevate CK activity
2. Serum should be stored in a dark place because CK is
inactivated by light
3. because of the effect of muscular activity and muscle mass
on CK levels, it should be noted that peopla who are physically
well trained tend to have elevated baseline levels
4. patients who are bedridden for prolonged periods may have
decreased CK activity
ACID PHOSPHATASE
E.C. 3.1.3.2
ACID PHOSPHATASE (E.C. 3.1.3.2)

• ACP belongs to the same group of phosphatase enzymes as ALP

• a hydrolase
• Functions at an optimal pH of approx. 5.0

TISSUE SOURCES:
• Prostate, bone, liver, spleen, kidney, erythrocytes, and platelets
ISOENZYMES
BAND 1 Prostatic ACP ( Inhibited by tartrate)

BANDS 2 and 4 Granulocytes

BAND 3 Platelets, RBCs & Monocytes ( major form in

plasma)
Red cell ACP- inhibited by cupric sulfate and 2%
formaldehyde)
BAND 5 Bone - osteoclasts ( resistant to tartrate inhibition)
ACP ELEVATION:
❖ Prostatic isoenzyme
•Prostatic Cancer: ACP is inferior to
PSA
•Prostatic hyperplasia & prostatic
infarction
•Urinary tract obstruction, carcinoid
tumors of rectum & prostatic
massage, prostatic manipulations
•Medico-legal:
❑ suspected rape
❑ACP in semen: first 12 hrs up to
4 days
❖Bone isoenzyme
•Active osteoclast-mediated bone
resorption
•Gaucher’s cells
•Hairy cell leukemia
 MEASUREMENT OF
ACP ACTIVITY
METHODS SUBSTRATE END-PRODUCTS

1. Gutman & Phenylphosphate Inorganic PO4

Gutman
2. Shinowara PNPP p-nitrophenol
3. Babson, Read & Alpha-naphthyl PO4 Alpha-naphthol
Phillips

4. Roy and Hillman Thymolphthalein Free thymolphthalein

monophosphate
NOTES TO REMEMBER:

1. Serum must be free from hemolysis

2. Serum ACP decreases within 1-2 hours if
left at room temperature.
3. If not assayed immediately: serum
should be frozen or acidified to a pH
lower than 6.5
CHLORIDE
 CHLORIDE
• Major extracellular anion
• Represents the largest fraction of the plasma total
inorganic anion concentration (~154 mmol/L)
•It is the only anion to serve as an enzyme activator

• In RBCs : 45 – 54 mmol/L
• In tissue cells : ~1.0mmol/L
Chloride’s role in electrical neutrality
1. Na+ is reabsorbed along w/ Clin the PCT & LH
• chloride acts as the rate limiting component

2. Chloride shift
DIAGNOSTIC SIGNIFICANCE:
1. HYPOCHLOREMIA- decrease plasma concentration of Chloride
• vomiting
• diabetic ketoacidosis
• aldosterone dificiency
• salt-losing renal disease( Pyelonephritis)
• elevated serum bicarbonate ( metabolic alkalosis)
2. HYPERCHLOREMIA- increase plasma concentration of Chloride
• occurs when there is an excess loss of bicarbonate ( metabolic
acidosis)
• dehydration
• renal tubular acidosis
Determination:
SPECIMEN:
• serum/plasma ( Lithium heparin)
• Chloride is stable in serum for 1 day at RT, 3 months frozen
• WB ( check for the instrument's operation manual)
• hemolysis does not cause a significant change in serum/ plasma
• 24- hour urine
• sweat
METHODS:
1. ISE- most commonly used
2. Amperometric- coulometric titration- uses silver ions which
combine

Ag2 + 2 Cl- Ag Cl 2

3. Mercurimetric titration ( Schales and Schales Method)

Indicator: diphenylcarbazone
End product: Hg Cl2
4. Whitehorn Titration Method
• done using spectrophotometric reading
reagent: diphenylcarbazone
end product: reddish complex
Activity No. 12: DETERMINATION OF CHLORIDE
Colorimetric Method Based on the Modification of Skeggs and
Hochestrasser
Principle:

Hg(SCN)2 + 2Cl- ____________> HgCl2 + 2SCN

3SCN - + Fe3+ ___________ > 4 Fe(SCN)2 red complex
REAGENT COMPOSITION:

1. Chloride reagent: it is POISONOUS. It contains mercury and methanol

2. Chloride calibrator: 100 mEq/L
TRACE METALS
TRACE ELEMENTS
1. ESSENTIAL TRACE ELEMENTS
• if a deficiency impairs a biochemical or functional process and
replacement of element corrects impairment

2. NON-ESSENTIAL TRACE ELEMENTS

• of medical importance because many of them toxic
IRON
• Most abundant trace element in the body
• 40 to 50 mg iron/ kg body weight
• important in the metabolism such as collagen, tyrosine and catecholamines.

• DISTRIBUTION:
• hemoglobin in RBCs
• Ferritin and hemosiderin as iron stores
• body tissues- myoglobin and non-heme enzymes
• Iron bound to transferrin
DIAGNOSTIC SIGNIFICANCE:
IRON DEFICIENCY:
Due to:
• Increased blood loss
• decreased dietary intake
• decreased release from ferritin

IRON DEPLETION: Iron storage: decreased or absent

common causes: Blood loss due to GIT bleeding, Chronic drug ingestion,
parasite infestation, impaired absorption of iron and renal failure
Iron deficiency anemia- most advanced stage of iron deficiency
IRON OVERLOAD
• aka hemochromatosis (HH)
CAUSES:
• Hereditary HH- Primary iron overload ( affects liver function, often
leads to hyperpigmentation of the skin)
• cardiac arrythmia
• cirrhosis
• hypothyroidism
• impotence
• liver cancer
TREATMENT:
• therapeutic phlebotomy
• administration of chelators ( deferoxamine)
Secondary iron overload ( not genetic)
• excessive dietary, medicinal, or transfusion iron intake
• metabolic dysfunction

HEMOSIDEROSIS- increased serum iron and TIBC or transferrin, in the

absence of demonstrable tissue damage
Analytical methods for iron
1. Direct measurements
• quantitative, specific, & sensitive
• involve invasive procedures

2. Indirect method
• Colorimetric
• AAS
ZINC
• is the second most abundant trace metal in the body
• known to be a cofactor for almost 300 enzymes
• absorption mainly occurs in the small intestine and especially in the
jejunum
• used for the treatment of Wilson's disease
• DISTRIBUTION: muscle- 60%, skeleton- 30%, other tissues- 10%
Factors increasing zinc
absorption
• animal proteins and amino
acids in a meal
• intake of calcium
• unsaturated fatty acids
Factors decreasing zinc
absorption
• intake of iron
• taking zinc on an empty stomach
• presence of copper at high levels
• age
DIAGNOSTIC SIGNIFICANCE
ZINC DEFICIENCY
• Diabetes mellitus
• Alcohol abuse
• Malabsorption syndrom
• Liver and kidney disease
• acrodermatitis enteropathica ( Zn malabsorption in infants)
If symptoms of acrodermatitis enteropathica
progress:
• growth retardation
• diarrhes
• impared T-cell immunity
• insufficient wound healing
• infections
• delayed testicular development in adolescence
• earl death
Zn deficiency in adolescents:
• slow growth or weight loss
• altered taste
• delayed puberty
• dwarfism
• impaired dark adaptation
• alopecia
• emotional instability
• tremors
in SEVERE CASES: lymphopenia and death
Zn high doses may lead to:
• GIT symptoms
• decrease in heme synthesis
• hyperglycemia
Analytical methods
CONSIDERATIONS:
• diurnal variation
• postprandial variation
• RBC has 10x more zinc than plasma

Reference method: AAS

COPPER
• Copper is the third most abundant trace metal in the body
• important cofactor for several metalloenzymes
• for the reduction of iron in heme synthesis.
• cellular synthesis
• DNA and RNA reproduction
• sequestration of free radicals
Intake and Excretion of copper
DIAGNOSTIC SIGNIFICANCE
COPPER DEFICIENCY
• Premature infants and undernourished children
• Contributing factor in adults w/ osteoporosis & CVD
• Menke’s disease or “kinky hair syndrome”
• Diminished copper conc. in hair
• Decrease in ceruloplasmin
Signs of copper deficiency:
• neutropenia and hypochromic anemia in the early stages,
• osteoporosis and various bone and joint abnormalities
• decreased pigmentation of the skin and general pallor
• neurologic abnormalities(hypotonia, apnea, psychomotor
retardation)
COPPER TOXICITY
• An increased tissue and serum levels of copper
• Because of its redox potential, copper is an irritant to epithelia and
mucous membranes and can cause hepatic and renal damage with
hemolysis

WILSON'S DISEASE
• is a genetically determined copper accumulation disease that causes
copper deposits in tissues (liver, brain & cornea)
MANIFESTATIONS OF WILSON'S
DSE
• Neurologic disorders
• liver dysfunction
• KayserFleischer rings in the
cornea
TREATMENT:
zinc acetate or chelation therapy
Diagnostic steps in the Dx of Wilson's Dse
• Serum ceruloplasmin levels
• direct measurement of free copper

LABORATORY EVALUATION OF COPPER STATUS

• AAS- method of choice
• colorimetric methods

LABORATORY DETERMINATION OF CERULOPLASMIN:

• photometric
• immunochemical
 ULTRA-TRACE ELEMENTS
Element Function Deficiency Toxicity

CHROMIUM enhances insulin action; • insulin resisitance skin ulcers, renal and
for glucose and lipid hepatic necrosis
metabolism • Hyperlipidemia

• impaired glucose
tolerance ( DM Type
2)

COBALT hemoglobin synthesis • anemia heart failure

component of Vitamin • growth depression hypothyroidism
B12
ELEMENT FUNCTION DEFICIENCY TOXICITY
FLUORIDE Prevents dental carries dental carries

MANGANESE bone and connective skeletal defects psychiatric disorders

tissue function parknson's disease

MOLYBDENUM DNA metabolism Growth depression anemia

cretinism thyrotoxicosis
goiter

SELENIUM • prevents oxidative keshan disease hair and nail loss, liver
damage of lipid failure
• Cofactor in
glutathione
peroxidase and
iodothyronine
deiodinase
TOXICOLOGY
Toxicology
• is the study of the adverse effects of xenobiotics in humans.
• Xenobiotics are chemicals and drugs that are not normally found in or
produced by the body
4 MAJOR DISCIPLINES:
1. mechanistic
2. descriptive
3. forensic
4. clinical
Mechanistic toxicology

• elucidates the cellular, molecular, and biochemical effects of toxins

• provide a basis for rational therapy design
• to assess the degree of exposure in individuals.
Descriptive toxicology
• uses the results from animal experiments to predict what level of
exposure will cause harm in humans

Forensic toxicology
• concerned with the medicolegal consequences of toxin exposure.

Clinical toxicology
• is the study of interrelationships between toxin exposure and disease
states.
ROUTES OF EXPOSURE
1. Ingestion- is most often
observed in the clinical setting
2. inhalation
3. Transdermal
Terminologies:
1. Acute toxicity- single, short-term exposure to a substance
2. Chronic toxicity- repeated exposure for extended period of time.
3. TD50- is the dose that would be predicted to produce a toxic
response in 50% of the population.
4. LD50- is the dose that would predict death in 50% of the population
5. ED 50- is the dose that would be predicted to be effective or have a
therapeutic benefit in 50% of the population.
Section 1. DRUGS OF ABUSE
• almost all drugs of abuse are basic drugs ( amine derivatives) which
contain benzene rings; barbiturates ( acidic drugs)

Nature of drug dependence:

1. Psychological - is when a person develops an uncontrollable “craving”
for a drug.
2. physiological - the body continually needs to have the drug, a person
experience sickness if drug is discontinued.
Six Categories of Drugs of abuse
1. Opiates and Narcotic Drugs
• are capable of analgesia, sedation, and
anesthesia
• they are derived chemically from opium poppy
Naturally occuring opiates: opium, morphine,
codeine
Chemically modified opiates: heroin,
hedromorphone, and oxycodone ( percodan)
A. Morphine
• is a metabolite of heroin, a powerful analgesic, for the
treatment of Acute Congestive Heart Failure
B. Opium
• psychologically addictive drugs; withdrawal causes
severe physiological symptoms
C. Codeine
• second most abundant component of opium, used as
a strong painkiller and cough suppressant
TOXIC EFFECTS: respiratory acidosis, myoglobinuria,
cardiopulmonary failure and pupillary constriction (
pin-point pupils)
2. Stimulants
• are taken to make one feel more energetic, strong, or awake

A. Amphetamine- used to treat ADHD and narcolepsy

B. Methamphetamine is the drug most commonly produced in

clandestine labs. Also known as meth, blue, ice, and crystal, white
powder
• originally used as nasal decongestant and bronchial inhaler
• 3,4 methylenedioxymethamphetamine ( MDMA/ ecstasy): a derivative
of methamphetamine
C. Cocaine
• very powerful stimulant; enormously psychologically addicting
• Cocaine hydrochloride is usually inhaled through the nose
• used as a local anesthetic for nasopharyngeal surgery
• it crosses the placenta and mammary glands
• for single use, it can be detected in urine up to 3 days; up to 20 days
for chronic users
• URINE METABOLITE: Benzoylecgonine ( sensitive and specific
indicator)
• TOXIC EFFECTS: hypertension, arrythmias, seizures, and MI
3. HALLUCINOGENS
Physiolgically active ingredients: cannabinoids
Most common Naturally occurring cannabinoids: marijuana and hashish
A. MARIJUANA
Most active cannabinoid: THC ( tetrahydrocannabinol)
Principal psychoactive ingedient: delta-9-tetrahydrocannabinol
Urinary metabolite: 11-nor- deltatetrahydrocannabinol/ 11-hydroxy-
delta 9- THC ( THC-COOH)
• after a single use, TCH-COOH can be detected in urine for 3-5 days; up
to 4 weeks for chronic users
B.HASHISH
• more potent form of marijuana made from the flowering tops of the
plant

C. LSD- Lysergide ( Lysergic acid diethylamide)

• is an extremely potent hallucinogen with normal dose of 30-50 mg, this
causes visual hallucinations, brilliant colors and the perception that one
is wise.
• Most adverse reaction: Panic reaction - “Bad trip”
• Toxic effects: blurred or “undulating” vision and synesthesia
4. DEPRESSANTS, HYPNOTICS, AND TRANQUILIZERS

A. ALCOHOL ( DEPRESSANT)- most abused substance

B. BARBITURATES ( sedative hypnotic) - physiologically active

depressants, resulting in a physical & mental state similar to alcohol-
induced intoxication
• are condensation products of urea and malonic acid
• they increase gamma aminonutyric acid ( GABA) activity in the brain
Commonly abused barbiturates: secobarbital, pentobarbital,
phenobarbital, thiopental

Toxic effects: Cheyne-Stokes respiration, depression, cyanosis,

areflexia, stupor, coma
C. BENZODIAPINES- are used for treatment of cocaine addiction

a. Valium/Diazepam- a tranquilizer drug designed to relieve anxiety

b. Rohypnol- “ roofies”
• It is used in the short-term treatment of insomnia, as a pre-
medication in surgical procedures and for inducing anesthesia.
• “ date-rape drug”
5. CLUB DRUGS

A. MDMA ( 3-4 methylenedioxymethamphetamine)

• love drug/ ecstasy
• increases brain chemicals: dopamine, norepinephrine, serotonin

B. GHB( gamma hydroxybutyrate)- used for their hypnotic or depressant

effects.
• used as general anesthetic and as a treatment for cataplexy, narcolepsy,
and alcoholism.
C. Ketamine - anesthetic and animal tranquilizer; causes anterograde
amnesia

6. ATHLETIC PERFORMANCE ENHANCERS

A. anabolic steroids
• promotes cell growth resulting in growth of muscle tissue and
sometimes bone size and strength