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INTESTINAL WALL
TYRAMINE
ISOPRENALINE
STILBESTROL
TESTOSTERONE
PROGESTERONE
CHLORPROMAZINE
LEVODOPA
ALFAMETHYLDOPA
FIRST PASS METABOLISM CONTINUED
LIVER LUNGS
NITRATES ISOPRENALINE
OPIOIDS NICOTINE
Β –BLOCKERS (LIPID SOLUBLE)
LIGNOCAINE
CLARITHROMYCIN
SAQUINAVIR
VORICONAZOLE
VERAPAMIL
TCAD’s
SIGNIFICANCE OF PLASMA PROTEIN BINDING
• SERVES AS A TEMPORARY DRUG RESERVOIR
• PHARMACOLOGICALLY INACTIVE. ONLY FREE FORM IS
ACTIVE
• NOT METABOLISED IN LIVER
• NOT FILTERED BY KIDNEY, BUT IS SECRETED FROM
PLASMA TO RENAL TUBULAR LUMEN
• DRUG-DRUG INTERACTIONS WITH HIGHLY PROTEIN
BOUND DRUGS
SIGNIFICANCE OF PLASMA PROTEIN BINDING
CONTINUED
• HIGHLY PROTEIN BOUND DRUGS ARE
DIFFICULT TO DIALYSE
• HIGH PROTEIN BOUND DRUG HAS POOR
ENTRY INTO CSF
• CAN DETERMINE HALF LIFE OF DRUG
EXAMPLES OF PLASMA PROTEIN BINDING
HIGH BINDING LOW BINDING
WARFARIN SODIUM REGULAR INSULIN
PHENYTOIN HEPARIN
CARBAMAZEPINE METRONIDAZOLE
SODIUM VALPROATE DIGOXIN
PIROXICAM PENICILLIN-G
SULFADOXINE CHLORTHIAZIDE
CISPLATIN VANCOMYCIN
QUININE
CONTINUED HIGH PROTEIN BINDING
SALICYLATES AZITHROMYCIN
INDOMETHACIN CLINDAMYCIN
MEFLOQUINE PHENYLBUTAZONE
DAPSONE TOLBUTAMIDE
CHLORPROPAMIDE
CHLORTHALIDONE
AMIODARONE
TEICOPLANIN
DRUG IDIOSYNCRASY EXAMPLES
• CHLORAMPHENICOL APLASTIC ANEMIA
• SUCCINYLCHOLINE + HALOTHANE MALIGNANT
HYPERTHERMIA
• CHLORPROMAZINE CHOLESTATIC JAUNDICE
• THIAZIDE DIURETICS ERECTILE DYSFUNCTION
• VANCOMYCIN RED MAN SYNDROME
• ASPIRIN INDUCED LATE ONSET ASTHMA
EXAMPLES OF PHARMACOGENETICS
• INH SLOW AND FAST ACETYLATORS (AR)
• SUCCINYLCHOLINE PROLONGED APNOEA DUE TO
ATYPICAL PSEUDOCHOLINE ESTERASE(AR)
• HEMOLYTIC ANEMIA IN G6PD DEFICIENCY (AR)
• PHENYTOIN SLOW HYDROLYSIS (AR)
• BARBITURATES CAUSING ACUTE PORPHYRIA (AD)
COMPARISON BETWEEN TOLERANCE AND TACHYPHYLAXIS
TOLERANCE TACHYPHYLAXIS
• DEFINITION • DEFINITION
• MOA: DOWNREGULATION • DEPLETION OF
OF RECEPTORS NEUROTRANSMITTER NOR-
ADRENALINE FROM
POSTGANGLIONIC
SYMPATHETIC NERVE
ENDINGS
• TAKES TIME TO DEVELOP
• CAN BE PRODUCED ACUTELY
COMPARISON BETWEEN TOLERANCE AND
TACHYPHYLAXIS
TOLERANCE TACHYLPHYAXIS
• HAS CLINICAL SIGNIFICANCE • HAS NO CLINICAL
SIGNIFICANCE
• E.G’s: β2 AGONISTS, • INDIRECT
NITRATES, ALCOHOL, BDZ’s, SYMPATHOMIMETICS
BARBITURATES, OPIOIDS (TYRAMINE,
AMPHETAMINE,
EPHEDRINE)
ANTIOXIDANTS
DRUGS MINERALS
• ACEI’s MELATONIN • MANGANESE
• ARB’s • SELENIUM
• CARVEDILOL ADENOSINE • COPPER
• NICOTINAMIDE
• NEBIVOLOL
• SELIGILINE
DRUGS AS ANTIOXIDANTS
CONTINUED
• CHLOROQUINE
• TRIMETAZIDINE
• DESFERRIOXAMINE
• ALLOPURINOL
• LACTOFERRIN
OTHER ANTIOXIDANTS
VITAMINS FOOD SUBSTANCES
• BETACAROTENE ( • ISOFLAVONES
VIT A) (SOYABEAN)
• VITAMIN C • LYCOPENE (TOMATO)
• CURCUMINOIDS
• VITAMIN E
(TURMERIC)
• SPIRULINA (BLUE-
GREEN ALGAE)
SCHEDULE DRUGS
• SCHEDULE I : NOT USED CLINICALLY
E.G’s: LSD, HEROIN, MARIJUANA
COMPETITIVE NON-COMPETITIVE
• REVERSIBLE • IRREVERSIBLE
• SURMOUNTABLE • UNSURMOUNTABLE
• MAX RESPONSE OF AGONIST • MAX RESPONSE OF AGONIST
IS OBTAINED IN IS NOT OBTAINED IN THE
PRESENCE OF ANTAGONIST PRESENCE OF ANTAGONIST
• SHIFT TO THE RIGHT • SHIFT TO THE RIGHT
• PARALLEL • NOT PARALLEL
COMPARISON BETWEEN COMPETITIVE AND NON-COMPETITIVE
ANTAGONISM
COMPETITIVE NON-COMPETITIVE
• D-TC AND • PAPAVERINE /
NEOSTIGMINE ACETYLCHOLINE
• CHOL/ANTICHOL • PHENOXYBENZ/α -
• MORPHINE/NALOXONE RECEPTORS
• HIST/ANTIHISTAMINE • OP COMPS AND
CHOLINE ESTERASE
PHARMACOPOEIA
OFFICIAL BOOK CONTAINING DRUGS
PRESENT IN THE COUNTRY
IP (INDIAN PHARMACOPOEIA)
BP (BRITISH PHARMACOPOIEA)
USP (UNITED STATES PHARMACOPOIEA)
ESSENTIAL DRUG LIST CRITERIA (WHO)
• STANDARD QUALITY
• COST EFFECTIVE
• GOOD BIOAVAILABILITY
• LONG SHELF LIFE
• AVAILABLE 24 HRS
• WITHIN REACH (PROXIMITY)
• MEET MAJORITY OF PEOPLES NEEDS
• USED FOR MOST PREVALENT DISEASES
• COMMON INTERNATIONAL NON- PROPRIETARY NAMES
• INVESTIGATED IN HUMANS AND ANIMALS
FORMULAE FOR CHILD DOSE
YOUNG’S: AGE (YRS)
------------------ X ADULT DOSE
AGE + 12
CLARK’s: WT (LBS)
--------------- X ADULT DOSE
150
NON-MICROSOMAL:
Chloralhydrate ----- Trichloroethanol
CONTINUED BIOTRANSFORMATION EXAMPLES
• HYDROLYSIS: MICROSOMAL:
Pethidine ----- Pethidinic acid
NON-MICROSOMAL:
Ester local anaesthetics (Procaine etc.) ------PABA
Atropine ---- Tropic acid
Hydrolysis of β lactam ring
PHARMACOKINETICS
FIRST ORDER ZERO ORDER
• FRACTION OF DRUG • FIXED AMOUNT OF DRUG
ELIMINATED PER UNIT TIME ELIMINATED PER UNIT TIME
• INDEPENDENT OF DOSE • DOSE DEPENDENT
• DOES NOT ACCUMULATE • DRUG ACCUMULATES
• ENZYMES ARE INTACT • ENZYMES ARE SATURATED
• GRAPH PLOTTED IS A STRAIGHT • GRAPH PLOTTED IS A
LINE HYPERBOLA
PHARMACOKINETICS
FIRST ORDER ZERO ORDER
• ALSO CALLED • ALSO CALLED ZERO
LINEAR/EXPONEN ORDER KINETICS
TIAL KINETICS
• HALF LIFE CAN BE • CANNOT
DETERMINED DETERMINE HALF
LIFE
DRUGS HAVING LOW THERAPEUTIC INDEX (NEED
TDM)
ANTIEPILEPTICS (EXCEPT BENZODIAZEPINES
AMINOGLYCOSIDES
WARFARIN
ANTICANCER DRUGS
THEOPHYLLINE
HEAVY METALS
ANTIARRYTHMICS
PHENOTHIAZINES
DRUGS HAVING LOW THERAPEUTIC INDEX
(NEED TDM)
CARDIAC GLYCOSIDES
ORAL HYPPOGLYCEMICS
CLINDAMYCIN
CHLORAMPHENICOL
VANCOMYCIN
FLUROQUINOLONES
TRICYCLIC ANTIDEPRESSANTS (TCAD’S)
COMPARISON BETWEEN SIDE EFFECT, TOXIC EFFECT
AND ADVERSE EFFECT
SIDE EFFECT TOXIC EFFECT ADVERSE EFFECT
• INTRACELLULAR RECEPTORS:
NUCLEAR Estrogen, Thyroid hormone, Vit D, VitA
CYTOPLASMIC ACTH, Progestogen, Androgen