Biotransformation of drug

biotransformation of drug(metabolism)
for b.pharma,m.pharma students.

1. Biotransformation of drug (METABOLISM) PRESENTED BY: Gayatri sati B.Pharm (VII sem) D.V.C.P. Lalpur (Rudrapur)

2. Biotransformation Biotransformation of drugs is defined as the chemical conversion of one form to another. The term is used synonymously with METABOLISM. METABOLISM: It is a general term used for chemical transformation of xenobiotics and endogenous nutrients ( e.g.-Protein, carbohydrate and fats) within or outside the body.

3. Need for drug biotransformation XENOBIOTICS: All chemical substances that are not nutrients for the body and enter the body though, ingestion, inhalation or absorption are called as XENOBIOTICs (Greek; Xeons=foreign) or EXOGENOUS COMPOUNDS .

4. Function of biotransformation Pharmacological inactivation T oxicological activation/ Bio activation Pharmacological activation Active Inactive Phenytoin P-Hydroxy phenytoin Amphetamine Phenyl acetone Activation Reactive intermediates Isoniazid Tissue acylating intermediate Paracetamol Imidoquinone of N- hydroxylated metabolite Inactive(Pro drug) Active Aspirin Salicylic acid Phenacetin Paracetamol

5. No change in pharmacological activity Change in pharmacological activity Active Active Digitoxin Digoxin Diazepam Temazepam Iproniazid (Antidepressant) Isoniazid (Antituberculer) Diazepam (Tranquilizer) Oxazepam (Anticonvulsant)

6. Drug metabolizing organs Decreasing order of drug metabolising ability of various organs is- Liver>Lungs>Kidney>Intestine>Placenta>Adrenals>Skin Brain, Testes, muscles, spleen etc. also metabolise drugs but to a small extent.

7. Drug Metabolizing enzyme The enzymes are broadly divided into two categories:- Microsomal enzyme Non-microsomal enzyme Microsomal enzyme:- A group of enzymes associated with a certain particulate fraction of liver homogenate. These are a mixed function oxidase system or mono- oygenases. These requires NADPH and oxygen. The 2 most impotent microsomal enzyme. NADPH cyctochrome P450 Reductase, Cut.P450

8. Non Microsomal enzyme: These are present in the cytoplasm and mitochondria of hepatic cells as well as in other tissues including plasma. Enzymes occurring in organelles/ sites other than endoplasmic reticulum are called Non-microsomal enzymes.

9. Phases of biotransformation Phase I Reaction :- Oxidative reaction Reductive reaction Hydrolytic reaction Phase II Reaction:- Sulfate conjugation Glucuronide conjugation Glutathione conjugation Amino acid conjugation

10. Oxidation Reactions Process of addition of oxygen or removal of hydrogen from a drug molecule. Hydroxylation Phenytoin Hydroxyphenytoin Dealkylation Codeine Morphine S-oxidation Cimetidine Cimetidine sulfoxide Deamination Amphetamine Benzylmethylketone

11. Reduction reactions Addition of hydrogen or removal of oxygen from a drug molecule. Nitro Reduction: Chloramphenicol arylamine Keto Reduction: Cortisone hydrocortisone

12. Hydrolysis Process where a drug molecule is split by the addition of a molecule of water. Both microsomal and non microsomal enzymes maybe involved. E.g .: Acetylcholine+H2O Choline+ acetic acid

13. Phase II reaction Glucuronide conjugation

14. Glutathione conjugation

15. Sulfate conjugation

16. Factors affecting metabolism of drugs Physiochemical properties of the drug Molecular size pKạ acid/base characteristics Lipophilicity Steric characteristics Chemical factor Enzyme induction Enzyme inhibition

17. Biological factor Species difference Genetic differences Sex differences Age differences Diet

18. References Brahmankar D.M,Jaiswal Sunil; Biopharmaceutics and pharmacokinetics-A treatise, third edition 2017(reprint),published by vallabh prakashan Delhi page no.140-194. Kulkarni S.K., Pawar, shedbalkar; Biopharmaceutics and pharmacokinetics, first edition 2012(reprint), published by CBS publishers new Delhi. Page no.94-131 Paradkar A nant, Bakliwal Sunil, Biopharmaceutics and pharmacokinetics, fourth edition 2013,published by nirali parkashan Delhi, page no.4.1-4.14 https://en.m.wikipedia.org>wiki>biotransformation

19. Thank you