1. LOCUS OFLOCUS OF
ACTIONACTION
““RECEPTORS”RECEPTORS”
BoundBound
TISSUE
RESERVOIRS


Free Bound
SYSTEMIC
CIRCULATION
Free
drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
Bound Drug Metabolites
Free
* Schematic representation of the interrelationship of the absorption, distribution,
binding and excretion of a drug and its concentration at its locus of action.

2. BIOTRANSFORMATIONBIOTRANSFORMATION

3. BIOTRANSFORMATIONBIOTRANSFORMATION
►DefinitionDefinition
►ObjectivesObjectives
►SitesSites
►TypesTypes
►Biochemical ReactionsBiochemical Reactions
►Pattern of Biochemical ReactionsPattern of Biochemical Reactions
►Factors Affecting BiotransformationFactors Affecting Biotransformation

4. DEFINITION -DEFINITION -
BIOTRANSFORMATIONBIOTRANSFORMATION
BIO derived from GREEK Word BIOS meaning lifeBIO derived from GREEK Word BIOS meaning life
Transformation meaning alteration /Transformation meaning alteration / changechange

5. AIMS AND OBJECTIVESAIMS AND OBJECTIVES
The mechanisms involved in theThe mechanisms involved in the
biotransformation / metabolism of drugs arebiotransformation / metabolism of drugs are
discussed.discussed.
Biotransformation causes: -Biotransformation causes: -
1.1. Conversion ofConversion of PRODRUGPRODRUG toto ACTIVEACTIVE
DRUGDRUG
2.2. Conversion ofConversion of DrugDrug toto Inactive FormInactive Form
3.3. Conversion of aConversion of a DrugDrug to ato a ToxicToxic MetaboliteMetabolite

6. AIMS AND OBJECTIVESAIMS AND OBJECTIVES
A clinician must be well informed about theseA clinician must be well informed about these
processes to treat the patients without exposingprocesses to treat the patients without exposing
them to the harmful effects of drugs.them to the harmful effects of drugs.

7. BIOTRANSFORMATIONBIOTRANSFORMATION
Drugs are eliminated by biotransformation andDrugs are eliminated by biotransformation and
excretion intoexcretion into URINEURINE oror BILEBILE..
Major site of drugs biotransformation isMajor site of drugs biotransformation is
LIVERLIVER..

8. PRODRUGPRODRUG
► Chloral hydrateChloral hydrate
► PhenacetinPhenacetin
► 6- Mercaptopurine6- Mercaptopurine
► CortisoneCortisone
► PrednisonePrednisone
► Tal – AmpicillinTal – Ampicillin
Piv – AmpicillinPiv – Ampicillin
Bac – AmpicillinBac – Ampicillin
► ChlorazepateChlorazepate
► EnalaprilEnalapril
ACTIVE DRUGACTIVE DRUG
TrichloroethanolTrichloroethanol
ParacetamolParacetamol
6- Mercaptopurine6- Mercaptopurine
ribonucleotideribonucleotide
HydrocortisoneHydrocortisone
PrednisolonePrednisolone
AmpicillinAmpicillin
AmpicillinAmpicillin
AmpicillinAmpicillin
DesmethyldiazepamDesmethyldiazepam
(Nordazepam)(Nordazepam)
EnalaprilatEnalaprilat

9. ADVANTAGES OF ADMINISTRATION OF AADVANTAGES OF ADMINISTRATION OF A
PRODRUGPRODRUG
► To make a drug tasteless and more stable e.g.To make a drug tasteless and more stable e.g.
Propoxyphene hydrocloride (bitter and unstable)Propoxyphene hydrocloride (bitter and unstable) 
Propoxyphene Naphsylate (tasteless & stable).Propoxyphene Naphsylate (tasteless & stable).
► To make the drug more palatable e.g. ChloramphenicolTo make the drug more palatable e.g. Chloramphenicol
Palmitate is given instead of Chloramphenicol.Palmitate is given instead of Chloramphenicol.
► To improve the rate of absorption of a drug e.g.To improve the rate of absorption of a drug e.g.
Tal – Ampicillin, Piv – Ampicillin & Bac – Ampicillin areTal – Ampicillin, Piv – Ampicillin & Bac – Ampicillin are
given instead of Ampicillin.given instead of Ampicillin.

10. ► To reduce the toxicity of a drug e.g. Tal – Ampicillin,To reduce the toxicity of a drug e.g. Tal – Ampicillin,
Piv – Ampicillin & Bac – Ampicillin are given insteadPiv – Ampicillin & Bac – Ampicillin are given instead
of Ampicillin.of Ampicillin.
► To increase the concentration of a drug at its site ofTo increase the concentration of a drug at its site of
action e.g. Levodopa in place of Dopamine.action e.g. Levodopa in place of Dopamine.
► To increase the duration of action of a drug e.g.To increase the duration of action of a drug e.g.
PhenothiazinePhenothiazine  Fluphenazine (ester derivatives likeFluphenazine (ester derivatives like
Fluphenazine enanthate, Fluphenazine decanoate).Fluphenazine enanthate, Fluphenazine decanoate).

11. BIOTRANSFORMATIONBIOTRANSFORMATION
SITESSITES
Liver, GIT, Lungs, Skin, Kidneys, Adrenals, Blood.Liver, GIT, Lungs, Skin, Kidneys, Adrenals, Blood.
LiverLiver :-:- Meperidine, Pentazocine, Morphine, Nitroglycerine,Meperidine, Pentazocine, Morphine, Nitroglycerine,
Lignocaine, Propranolol, Paracetamol, PrazosinLignocaine, Propranolol, Paracetamol, Prazosin
GIT:-GIT:- Insulin. Catecholamines. Clonazepam, Chlorpromazine,Insulin. Catecholamines. Clonazepam, Chlorpromazine,
Tyramine & SalbutamolTyramine & Salbutamol
Lungs:-Lungs:- Prostanoids (prostaglandins & thromboxanes)Prostanoids (prostaglandins & thromboxanes)
Plasma:-Plasma:- Suxamethonium (succinylcholine)Suxamethonium (succinylcholine)
Procaine, Propanidid, Aspirin, ClofibrateProcaine, Propanidid, Aspirin, Clofibrate

12. FIRST-PASS EFFECTFIRST-PASS EFFECT OROR PRESYSTEMICPRESYSTEMIC
METABOLISMMETABOLISM

13. Drugs undergoing extensive first-pass effectDrugs undergoing extensive first-pass effect
►LignocaineLignocaine
►NitroglycerineNitroglycerine
► InsulinInsulin
►Sympathomimetic catecholaminesSympathomimetic catecholamines
►MorphineMorphine
►MeperidineMeperidine
►PentazocinePentazocine
►ChlorpromazineChlorpromazine
►ClonazepamClonazepam

14. BIOTRANSFORMATIONBIOTRANSFORMATION
REACTIONSREACTIONS
The kidney cannot efficiently eliminateThe kidney cannot efficiently eliminate
LipophilicLipophilic DrugsDrugs that readily cross cellthat readily cross cell
membrane and are reabsorbed in the distalmembrane and are reabsorbed in the distal
tubules.tubules.
The lipid soluble agents must, therefore,The lipid soluble agents must, therefore,
undergo biotransformation in the liver.undergo biotransformation in the liver.

15. BIOTRANSFORMATIONBIOTRANSFORMATION
Drug biotransformation reactions are classified as:Drug biotransformation reactions are classified as:
PHASE 1 REACTIONSPHASE 1 REACTIONS
OxidationOxidation
ReductionReduction
HydrolysisHydrolysis

16. BIOTRANSFORMATIONBIOTRANSFORMATION
PAHSE 2 REACTIONSPAHSE 2 REACTIONS
Conjugation ReactionsConjugation Reactions
 GlucuronidationGlucuronidation
 SulfationSulfation
 AcetylationAcetylation
Conjugates are generally Inactive and areConjugates are generally Inactive and are
excreted rapidly in urine and fecesexcreted rapidly in urine and feces

20. TYPESTYPES
a.a. Non-enzymaticNon-enzymatic
b.b. EnzymaticEnzymatic
b. Enzymaticb. Enzymatic
a.a. MicrosomalMicrosomal
b.b. Non-microsomalNon-microsomal
BIOTRANSFORMATION

21. NON-ENZYMATICNON-ENZYMATIC
BIOTRANSFORMATIONBIOTRANSFORMATION
(HOFMANN ELIMINATION)(HOFMANN ELIMINATION)
Mustine HClMustine HCl (Mechlorthamine) Ethyleneimonium(Mechlorthamine) Ethyleneimonium
AtracuriumAtracurium Laudanosine & Quaternary acidLaudanosine & Quaternary acid
HexamineHexamine (at acidic pH of urine) Formaldehyde(at acidic pH of urine) Formaldehyde
ChlorazepateChlorazepate DesmethyldiazepamDesmethyldiazepam
(at acidic pH in the stomach)(at acidic pH in the stomach)

22. PHASE - I REACTIONSPHASE - I REACTIONS
(non-synthetic / catabolic)(non-synthetic / catabolic)
I.I.OXIDATIONOXIDATION:-:-
Microsomal Catalysed by Microsomal EnzymesMicrosomal Catalysed by Microsomal Enzymes
Non-Microsomal Catalysed by Non-Microsomal EnzymesNon-Microsomal Catalysed by Non-Microsomal Enzymes
A.A.MICROSOMAL OXIDATIONMICROSOMAL OXIDATION
 HYDROXYLATIONHYDROXYLATION
a.a. HYDROXYLATION OF AROMATIC RING.HYDROXYLATION OF AROMATIC RING.
PHENOBARBITONE P-HYDROXYPHENOBARBITONEPHENOBARBITONE P-HYDROXYPHENOBARBITONE
b.b. ALIPHATIC HYDROXYLATIONALIPHATIC HYDROXYLATION
MEPROBAMATE HYDRXYMEPROBAMATEMEPROBAMATE HYDRXYMEPROBAMATE
 N- DEALKYLATIONN- DEALKYLATION
MEPHOBARBITONE PHENOBARBITONEMEPHOBARBITONE PHENOBARBITONE

23.  O- DEALKYLATIONO- DEALKYLATION
CODEINE MORPHINECODEINE MORPHINE
 N-OXIDATIONN-OXIDATION
ANILINE NITROSOBENZENEANILINE NITROSOBENZENE
 SULFOXIDATIONSULFOXIDATION
CHLORPROMAZINE CHLORPROMAZINE SULFOXIDECHLORPROMAZINE CHLORPROMAZINE SULFOXIDE
 DEAMINATIONDEAMINATION
AMPHETAMINE PHENYLACETONEAMPHETAMINE PHENYLACETONE
 DESULFURATIONDESULFURATION
PARATHION PARAOXONPARATHION PARAOXON

24. B.B. NON -NON - MICROSOMALMICROSOMAL OXIDATIONOXIDATION
ETHANOLETHANOL ACETALDEHYDE ACETIC ACIDACETALDEHYDE ACETIC ACID
HYPOXANTHINEHYPOXANTHINE XANTHINE URIC ACIDXANTHINE URIC ACID
II.II. REDUCTIONREDUCTION
CHLORAMPHENICOLCHLORAMPHENICOL ARYLAMINEARYLAMINE
CHLORAL HYDRATECHLORAL HYDRATE TRICHLOROETHANOLTRICHLOROETHANOL
OO
III.III. HYDROLYSISHYDROLYSIS ((Drugs having ester linkageDrugs having ester linkage:-C—O—C):-C—O—C)
PROCAINEPROCAINE PABA+DIETHYLAMINOETHANOLPABA+DIETHYLAMINOETHANOL
ACETYLCHOLINEACETYLCHOLINE
SUXAMETHONIUMSUXAMETHONIUM
PropanididPropanidid

33. GDP

34. Hepatic microsomal enzymes
(oxidation, conjugation)
Extrahepatic microsomal enzymesExtrahepatic microsomal enzymes
(oxidation, conjugation)(oxidation, conjugation)
Hepatic non-microsomal enzymesHepatic non-microsomal enzymes
(acetylation, sulfation, GSH,(acetylation, sulfation, GSH,
alcohol/aldehyde dehydrogenase,alcohol/aldehyde dehydrogenase,
hydrolysis, ox/red)hydrolysis, ox/red)
Drug Metabolism

35. Microsomal Mixed Function Oxidase
System showing Cytochrome P-450
cycle in drug oxidations
COMPONENTS
Cytochrome P-450 (P-450-Fe3+
)
Cytochrome P-450 Reductase (P-450-Fe2+
)
NADPH
Flavoprotein
Molecular Oxygen
Membrane Lipid

36. Microsomal Mixed Function Oxidase
System showing Cytochrome P-450
cycle in drug oxidations
COMPONENTS
Cytochrome P-450 (P-450-Fe3+
)
Cytochrome P-450 Reductase (P-450-Fe2+
)
NADPH
Flavoprotein
Molecular Oxygen
Membrane Lipid
Drug Substrate
Figure 4-3. Cytochrome P-450
Cycle in drug oxidations (RH=par-
ent drug ROH = oxidized metabolite
Fp = flavoprotein, e = electron)

37. PHASE - II REACTIONS:PHASE - II REACTIONS:
(CONJUGATION / SYNTHETIC / ANABOLIC REACTIONS)(CONJUGATION / SYNTHETIC / ANABOLIC REACTIONS)
GLUCURONIDE CONJUGATION occurring with phenols, alcohols,GLUCURONIDE CONJUGATION occurring with phenols, alcohols,
carboxylic acids and compounds containing amino or sulphydryl groupscarboxylic acids and compounds containing amino or sulphydryl groups
Acetaminophen, Morphine, Digitoxin,Acetaminophen, Morphine, Digitoxin,
GLYCINE CONJUGATIONGLYCINE CONJUGATION
Salicylic acid, Aspirin, Benzoic AcidSalicylic acid, Aspirin, Benzoic Acid
SULPHATE CONJUGATION occurring withSULPHATE CONJUGATION occurring with
phenols, alcohols, and aromatic aminesphenols, alcohols, and aromatic amines
Methyldopa, ParacetamolMethyldopa, Paracetamol
ACETYLATIONACETYLATION
Sulfonamides, INH, DapsoneSulfonamides, INH, Dapsone
GLUTATHION CONJUGATIONGLUTATHION CONJUGATION
Ethacrynic Acid, N-acetyl-p-benzoquinoneimine– reactive phase 1Ethacrynic Acid, N-acetyl-p-benzoquinoneimine– reactive phase 1
metabolite of acetaminophenmetabolite of acetaminophen
METHYLATIONMETHYLATION
Histamine , Adrenaline ,Nor-adrenaline, DopamineHistamine , Adrenaline ,Nor-adrenaline, Dopamine

38. PHASE -II REACTIONSPHASE -II REACTIONS
Type ofType of
ConjugationConjugation
EndogenousEndogenous
ReactantReactant
TransferaseTransferase
(Location)(Location)
ExamplesExamples
GlucuronidationGlucuronidation UDP-glucuronic acidUDP-glucuronic acid UDP-glucuronylUDP-glucuronyl
transferasetransferase
(microsomes)(microsomes)
Morphine,Morphine,
acetaminohpenacetaminohpen
AcetylationAcetylation Acetyl – CoAAcetyl – CoA N-Acetyl transferaseN-Acetyl transferase
(cytosol)(cytosol)
Sulfonamides,Sulfonamides,
isoniazidisoniazid
GlutathioneGlutathione
conjugationconjugation
GlutathioneGlutathione GSH-S-transferaseGSH-S-transferase
(cytosol, microsomes(cytosol, microsomes
Ethacrynic acid,Ethacrynic acid,
paracetamolparacetamol
GlycineGlycine
conjugationconjugation
GlycineGlycine Acyl-CoA glycineAcyl-CoA glycine
transferasetransferase
(mitochondria)(mitochondria)
Salicylic acid,Salicylic acid,
benzonic acidbenzonic acid
SulfateSulfate
conjugationconjugation
Phosphoadenosyl-Phosphoadenosyl-
PhosphosulfatePhosphosulfate
SulfotransferaseSulfotransferase
(cytosol)(cytosol)
Acetaminophen,Acetaminophen,
methyldopamethyldopa
MethylationMethylation S-S-
AdenosylmethionineAdenosylmethionine
TransmethylaseTransmethylase
(cytosol)(cytosol)
Dopamine,Dopamine,
epinephrineepinephrine

39. DRUG BIOTRANSFORMATIONDRUG BIOTRANSFORMATION
► Pattern of ReactionsPattern of Reactions
Phase-I Reaction is often followed by Phase-II Reaction.Phase-I Reaction is often followed by Phase-II Reaction.
Drug or its metabolite produced from Phase-I Reaction is conjugated with an endogenousDrug or its metabolite produced from Phase-I Reaction is conjugated with an endogenous
substrate during Phase-II Reaction.substrate during Phase-II Reaction.
Phase-I Reaction (Drug or its Metabolite) Phase-II ReactionPhase-I Reaction (Drug or its Metabolite) Phase-II Reaction (Conjugation)(Conjugation)

40. ExceptionsExceptions
► In some cases Phase-II reaction may precede phase-I reaction. e.g.In some cases Phase-II reaction may precede phase-I reaction. e.g.
IsoniazidIsoniazid
Phase-II reaction (acetylation) take place first and is then followed byPhase-II reaction (acetylation) take place first and is then followed by
phase-I reaction (Hydrolysis) as under:-phase-I reaction (Hydrolysis) as under:-
Phase-II Phase-IPhase-II Phase-I
Acetylation HydrolysisAcetylation Hydrolysis
DRUG BIOTRANSFORMATIONDRUG BIOTRANSFORMATION
INHINH N-acetyl INHN-acetyl INH Isonicotinic acid + acetylhydazineIsonicotinic acid + acetylhydazine

42. EFFECTS OF PHASE-I REACTIONS ON THEEFFECTS OF PHASE-I REACTIONS ON THE
SOLUBILITY AND ACTIVITY OF A DRUGSOLUBILITY AND ACTIVITY OF A DRUG
a.a. Lipid solubility of drugs partially converted into water solubility.Lipid solubility of drugs partially converted into water solubility.
b.b. Sometimes water solubility may be decreasedSometimes water solubility may be decreased
(diazepam desmethyldiazepam)(diazepam desmethyldiazepam)
c.c. A drug may be inactivated, activity may be increased or activity may beA drug may be inactivated, activity may be increased or activity may be
totally modified producing a highly toxic/ reactive / carcinogenictotally modified producing a highly toxic/ reactive / carcinogenic
product.product.
► Parathion is converted into highly toxic paraoxon.Parathion is converted into highly toxic paraoxon.
► Acetaminophen (Paracetamol) is converted intoAcetaminophen (Paracetamol) is converted into
highly toxic product (N-acetyl-p-highly toxic product (N-acetyl-p-
benzoquinoneimine).benzoquinoneimine).
► Diazepam converted to Oxazepam witch is moreDiazepam converted to Oxazepam witch is more
active.active.
d. On biotransformation, a drug may yield more than one active/ inactive
metabolites, some of them having longer half-life than that of the parent
drug. Diazepam NordazepamDiazepam Nordazepam

44. Effects of Phase – II Reactions on DrugsEffects of Phase – II Reactions on Drugs
aa. Generally. Generally Lipid solubility of drugs isLipid solubility of drugs is totally converted intototally converted into
water solubilitywater solubility..
b.b. Drugs areDrugs are generally inactivatedgenerally inactivated..
c.c. Sometimes drug is activated e.g.Sometimes drug is activated e.g.
Minoxidil is converted into active Minoxidil -o- sulphate.Minoxidil is converted into active Minoxidil -o- sulphate.
Morphine converted into active Morphine-6-glucuronide.Morphine converted into active Morphine-6-glucuronide.
dd. Conjugates may be secreted into the bile by an active transport. Conjugates may be secreted into the bile by an active transport
process;process; may be split up by the intestinal bacteriamay be split up by the intestinal bacteria causingcausing
release and reabsorption of active drug, thus establishingrelease and reabsorption of active drug, thus establishing
entero-hepatic circulation of the active drug prolonging itsentero-hepatic circulation of the active drug prolonging its
duration of actionduration of action
e.g. Doxycyline, oral contraceptive combined-pill.e.g. Doxycyline, oral contraceptive combined-pill.

45. FACTORS MODIFYINGFACTORS MODIFYING
BIOTRANSFORMATIONBIOTRANSFORMATION
►AGE.AGE.
 Chloramphenicol causes “Chloramphenicol causes “Gray Baby SyndromeGray Baby Syndrome””
 Diazepam produces ”Diazepam produces ”Floppy Baby syndromeFloppy Baby syndrome””
► ROUTE OF ADMINISTRATION.ROUTE OF ADMINISTRATION.
 11stst
Pass Effect:-Pass Effect:-
► LignocaineLignocaine
► NitroglycerineNitroglycerine
► InsulinInsulin
► Sympathomimetic catecholaminesSympathomimetic catecholamines
► MorphineMorphine
► MeperidineMeperidine
► PentazocinePentazocine
► ChlorpromazineChlorpromazine
► ClonazepamClonazepam

46. GENETIC FACTORS.GENETIC FACTORS.
 Atypical pseudocholinesterase:-Atypical pseudocholinesterase:- SuccinylcholineSuccinylcholine
(Suxamethonium) is hydrolysed by pseudocholinesterase.(Suxamethonium) is hydrolysed by pseudocholinesterase.
Genetically abnormal pseudocholinesterase Apnoea.Genetically abnormal pseudocholinesterase Apnoea.
 Acetylation status:Acetylation status: Slow & Fast acetylators Inherited as anSlow & Fast acetylators Inherited as an
autosomal recessive trait Slow acetylator phenotype – about 50autosomal recessive trait Slow acetylator phenotype – about 50
% 0f blacks & white in the USA Much less common in Asians &% 0f blacks & white in the USA Much less common in Asians &
eskimoseskimos
 Genetically determined defects in the CYP dependent oxidativeGenetically determined defects in the CYP dependent oxidative
metabolism of:metabolism of:
Debrisoquin, Phenacetin, Phenformin (extensive metabolizersDebrisoquin, Phenacetin, Phenformin (extensive metabolizers
and poor metabolizers)and poor metabolizers)
 Hydroxylation of anticonvulsant Mephenytoin:Hydroxylation of anticonvulsant Mephenytoin: PoorPoor
hydroxylators & Fast hydroxylatorshydroxylators & Fast hydroxylators

47. ► PATHOLOGICAL STATES OF:PATHOLOGICAL STATES OF:
► LIVER:-LIVER:- acute & chronic liver diseases, CA of liver depressacute & chronic liver diseases, CA of liver depress
metabolism of chloramphnical & diazepam increasing their plasmametabolism of chloramphnical & diazepam increasing their plasma
half-life.half-life.
► CVS:-CVS:- CCF decreases hepatic perfusion decreasing the clearance ofCCF decreases hepatic perfusion decreasing the clearance of
lidocaine.lidocaine.
► LUNGS:-LUNGS:- In pulmonary diseases, metabolism of procainamide andIn pulmonary diseases, metabolism of procainamide and
aminopyirne is depressed.aminopyirne is depressed.
► ENDOCRINES:-ENDOCRINES:- Hypothyroidism decreases the metabolism ofHypothyroidism decreases the metabolism of
digoxin, methimazole, practolol increasing their plasma half-life,digoxin, methimazole, practolol increasing their plasma half-life,
reverse happens in hyperthyroridism.reverse happens in hyperthyroridism.
► NUTRITIONAL STATUS:NUTRITIONAL STATUS:
► STARVATIONSTARVATION
► MALNUTRITIONMALNUTRITION
► SPECIESSPECIES (Phenylbutazone, Pethidine, Barbiturates)(Phenylbutazone, Pethidine, Barbiturates)
► SEXSEX (Hexobarbitone, BDZs, Oestrogens,(Hexobarbitone, BDZs, Oestrogens,
Salicylates)Salicylates)

48.  DRUG INTERACTIONS:DRUG INTERACTIONS:
Enzyme inductionEnzyme induction
Enzyme inhibitionEnzyme inhibition
Competitive substrate inhibitionCompetitive substrate inhibition

49. Enzyme InductionEnzyme Induction
Enzyme InducersEnzyme Inducers
PHENOBARBITONEPHENOBARBITONE
PHENYLBUTAZONEPHENYLBUTAZONE
PHENYTOINPHENYTOIN
MEPROBAMATEMEPROBAMATE
RIFAMPICINRIFAMPICIN
CARBAMAZEPINECARBAMAZEPINE
Ch. alcoholismCh. alcoholism
BENZOBENZO αα pyrene in Tobacco smokepyrene in Tobacco smoke
ClofibrateClofibrate
DEXAMETHASONEDEXAMETHASONE
Chronic AlcoholismChronic Alcoholism
WarfarinWarfarin

50. ENZYME INHIBITORSENZYME INHIBITORS
TypesTypes
• Competitive inhibitorsCompetitive inhibitors quinidinequinidine
• Reversible non - Competitive inhibitorsReversible non - Competitive inhibitors –– KETOCONAZOLEKETOCONAZOLE
• Suicide inhibitors- GestodeneSuicide inhibitors- Gestodene
CIMETIDINECIMETIDINE
KETOCONAZOLEKETOCONAZOLE
ERYTHOMYCINERYTHOMYCIN
CHLORAMPHENICOLCHLORAMPHENICOL
ISONIAZIDISONIAZID
PROPYLTHIOURACILPROPYLTHIOURACIL
ALLOBARBITONEALLOBARBITONE Suicide inhibitorsSuicide inhibitors
SECOBARBITONESECOBARBITONE
SPIRONOLACTONESPIRONOLACTONE
Inhibitors of intestinal P-gycoprotein (P-gp)Inhibitors of intestinal P-gycoprotein (P-gp)
VerapamilVerapamil
Certain components of grape fruit juiceCertain components of grape fruit juice
Drugs expelled by P-gp are digoxin, cyclosporineDrugs expelled by P-gp are digoxin, cyclosporine

51. Competitive substrate inhibitionCompetitive substrate inhibition
►Sulphonamides inhibit the metabolism ofSulphonamides inhibit the metabolism of
PhenytoinPhenytoin
►Phenylbutazone & coumarins inhibit thePhenylbutazone & coumarins inhibit the
metabolism of tolbutamide.metabolism of tolbutamide.

52. ►CIRCADIAN RHYTHMCIRCADIAN RHYTHM
►ENVIRONMENTAL FACTORS: Smoking,ENVIRONMENTAL FACTORS: Smoking,
Alcoholism, Exposure to Pesticides.Alcoholism, Exposure to Pesticides.
►CLIMATE & ALTITUDECLIMATE & ALTITUDE

53. BIOTRANSFORMATIONBIOTRANSFORMATION
BIOTRANSFORMATIONBIOTRANSFORMATION usually results inusually results in
the loss of Pharmacological activity, but therethe loss of Pharmacological activity, but there
are exceptions.are exceptions.
PRODRUGPRODRUG →→ ACTIVE DRUGACTIVE DRUG
DRUGDRUG →→ MORE ACTIVE COMPOUNDMORE ACTIVE COMPOUND
DRUGDRUG →→ TOXIC COMPOUNDTOXIC COMPOUND