Drug Metabolism | Drug Metabolism | Metabolism

Drug Metabolism

Lailaturrahmi 0811012047
Fakultas Farmasi Universitas Andalas

Definition
Drug metabolism is the chemical alteration of a drug by the body.

Effects of Drug Metabolism The drug is made more hydrophilic Metabolite is usually less active than parent drug (not always occurred) .

Location of Drug Metabolism Liver Lung Kidney Small intestine Colon Skin Adrenal gland .

In the liver. enzymes convert : ± prodrugs active metabolites ± active drugs inactive forms. which is the site of most drug metabolism.A vast majority of drugs pass through the liver. .

FirstFirst-pass effect/metabolism All orally administered drugs pass through the liver to the systemic circulation This term does not refer to hepatic metabolism only .

Drug Biotransformation Reactions Active drug to inactive metabolite ± Deamination (Amphetamine Phenylacetone) ± Hydroxilation (Phenobarbital Hydroxyphenobarbital) .

Active drug to active metabolite ± Demethylation (Codeine Morphine) ± Acetylation (Procainamide Nacetylprocainamide) ± Hydroxilation (Phenylbutazone Oxyphenbutazone) .

Inactive drug to active metabolite ± Hydrolysis (Hetacillin Ampicillin) ± Azoreduction (Sulfasalazine Sulfapyridine + 5-aminosalycilic acid) 5- Active drug to reactive metabolite ± Aromatic hydroxylation .

Pathway of Drug Biotransformation Phase I (asynthetic reactions) ± Oxidation ± Reduction ± Hydrolysis Phase II (synthetic reactions) ± Conjugation .

Hepatic Enzyme Involved in Metabolism Mixed function Oxidases Is responsible for reduction and oxidation of drugs and certain natural metabolites .

NADPH-cytochrome PNADPHP450 reductase. and cytochrome PP450 . reduction.Phase I reaction There are 3 common reactions : oxidation. O2. and hydrolysis Oxidation is the most common reaction The oxidation process involve NADPH.

sulphate. acetyl. glycine. methyl .Phase II reaction Involve conjugation of drug/phase I metabolites with endogenous substances Type of conjugation : glucoronide. glutathione.

Glucoronidation lucoronidation ± Conjugating agent : glucoronic acid ± High energy metabolite : uridine diphosphoglucoronic acid (UDPGA) ± Functional group combined with : -OH. COOH. -NH2. -SH .

.Sulfation ± Conjugating agent : sulfate ± High energy metabolite : 3'3'phosphoadenosine-5'phosphoadenosine-5'-phosphosulfate (PAPS) ± Functional group combined with : -OH. NH2.

Amino acid conjugation ± Conjugating agent : glycine ± High energy metabolite : Coenzyme A thioesters ± Functional group combined with : -COOH .

²NH2 .Acetylation ± Conjugating agent : Acetyl CoA ± High energy metabolite : Acetyl CoA ± Functional group combined with : ²OH.

²NH2 .Methylation ± Conjugating agent : CH3 from SSadenosylmethionine ± High energy metabolite : SSadenosylmethionine ± Functional group combined with : ²OH.

epoxides ± Functional group combined with : Aryl halides.Glutathione (mercapturine acid conjugation) ± Conjugating agent : Glutathione ± High energy metabolite : Arene oxides. arene oxides . epoxides.

Factor affecting drug metabolism Enzyme induction Enzyme inhibition Genetic polymorphism Age .

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