BIOTRANSFORMATION_presentation_2023 Sayan Ghosh.pptx

Sayan Ghosh

1. BIOTRANSFORMATION SAYAN GHOSH SONA GHOSH SOUBIRANJAN GHOSH SOUMI HAZRA MAIMUN HOSSAIN JUNAEID IFTAR PASHMIN KAUR SNEHA KHAMRUI SNEHA KHARE AZMUDA KHATUN ( SRIMS & SH ) Definition Consequences Phases classification Phases I & II details description First pass metabolism OVERVIEW

2. DEFINATION: Biotransformation means enzyme catalysed biochemical transformation of drugs within living organisms. Non polar lipid soluble polar water soluble so that they are easily excreted. ( streptomycin , neostigmine not undergoes biotransformation due to highly polar drugs) SITE: Liver (primary) & Kidney,Intestine,Lungs (secondary).

3. Active drug to inactive drug/Metabolites eg: Phenobarbitone 4-Hydroxyphenobarbitone (active drug) (inactive metabolite) Active drug to Active/Toxic metabolites eg: Diazepam Oxazepam (active) (Active) Inactive to Active drug eg: Levodopa Dopamine (pro drug) (Active) CONSEQUENCES

4. Biotransformation reactions can be classified into two phases Phase I/Nonsynthetic/Functionalisation reactions Degradative reactions,mainly microsomal . By generating functional Groups(-SH,-OH,COOH) --- metabolites may active or inactive. Phase II/Synthetic/conjugation reactions These reactions are catalysed by Mitrochondrial,microsomal or cytoplsmic enzymes. Metabolite formed is usually polar, water soluble and conjugated.

5. PHASE I 1.OXIDATION Process of addition of oxygen or removal of hydrogen. Eg: Codeine Morphine 2.REDUCTION Addition of hydrogen or removal of oxygen Eg: Cortisone Hydrocortisone 3.HYDROLYSIS Addition of water Eg: Acetylcholine + Water choline + acetic acid 4.CYCLIZATION Proguanil Cycloguanil (Chain) (Ring) Opening of ring structure eg: Barbiturates,phenytoin 5.DECYCLIZATION

6. PHASE II   1.GLUCURONIDE CONJUGATION Drug + UDPGA UGT Drug + UDP glucuronide Microsomal conjugation( by UDP glucuronyl transferase ) Eg: Morphine, Paracetamol etc 2.ACETYLATION   Non microsomal conjugation (by N-Acetyl transferase ) Acetyl CoA = cofactor Eg: Isoniazid, Hydralazine etc NAT 3.SULPHATE COJUGATION R-OH + PAPS + ADP   Non microsomal conjugation (by sulfotransferase ) Phenolic,alcholic compounds undergo this Conjugation Eg: Chloramphenicol, Aspirin etc SULT 4.METHYL CONJUGATION R- R-NH-   MT Non microsomal conjugation (by O-methyl transferase ) Amines and phenols undergo this reaction Eg: Methyldopa, Adrenaline etc 5.GLYCINE CONJUGATION Acyl-CoA derivatives of carboxylic acid Drugs couples with glycine Non microsomal conjugation(by glycine transferase ) Eg: Nicotinic acid, Salicylates etc 6.GLUTATHIONE CONJUGATION Non microsomal conjugation(by glutathione -s-transferase ) Quinine, epoxide undergoes this reaction Eg: Sulfobromopthalin, Paracetamol etc 7.RIBONUCLEOSIDE/NUCLEOTIDE SYNTHESIS Purines and pyrimidines undergo this reaction Used in Cancer Chemotherapy

7. :FIRST PASS METABOLISM: DEFINATION : Metabolism of a drug during its passage from the site of absorption into the systemic circulation. SIGNIFICANCE OF FIRST PASS METABOLISM (Pre-systemic metabolism): Oral dose is higher than parenteral or sublingual dose. Oral bioavailability is apparently increased in liver disease (like cirrhosis). Concurrent administration of another drug competing may increase the bioavailability (eg: Propranolol & Chlorpromazine ) HIGH FIRST PASS METABOLISM LOW FIRST PASS METABOLISM Lidocaine, Isoprenaline (not orally) Pindolol, Theophylline Glyceryl trinitrate, Salbutamol (high oral dose)

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