Metabolism (Biotransformation)

The Topic PHARMACOKINETICS & METABOLISM gives you detail information about (1st pass metabolism of drug, organs & enzymes involed in drug metabolism, All Phases of Drug) & All you need to know about BIO-TRANSFORMATION.

1. DEPARTMENT OF PHARMACOLOGY Topic Name : Pharmacokinetics Sub Topic Name : Metabolism

2. METABOLISM. [Biotransformation) 1 】 Defination 2 】 Organs & Enzymes involved in drug Metabolism 3 】 First pass Metabolism of Durg 4 】 Phases of Drug Metabolism 5 】 Factors Affecting Drug Metabolism

3. Biotransformation of Drug is defined as the conversion from one chemical from to another. The terms is used synonymously with Metabolism The Drug which are enter the through ingestion inhalation or absorption are called as xenobiotics (Greek: xenos =foreign) or exogenous compound DEFINITION

4. ORGANS : 1] Liver. 2] Lungs. 3] Kidney 4] Intestine 4] Plasenta 5] Adrenals 6] Skin 1) Liver is primary site for Metabolism of almost all drug because a large variety of Enzymes in large amount in Liver are present 2) Metabolism by organs other than liver called as extrahepatic Metabolism 3) The decreasing order of Drug Metabolism Ability of various Organs I.e Liver > Lungs > Kidney > Intestine > Plasenta > Adrenals > Skin 4) Brain , testes , Muscle , Spleen etc also metabolites drug to a Small extent https://www.google.co.in/search?q=diagram+for+the+Metabolism+on+the+basis+of+introduction&client=ms-android-xiaomi&prmd=inv&source=lnms&tbm=isch&sa=X&ved=0ahUKEwism92M_azXAhVENY8KHZ6fDSEQ_AUIEigB&biw=360&bih=564 https://www.google.co Organs Involved in Drug Metabolisum

5. Enzymes involved in Drug Metabolisum These Enzymes are broadly divided into 2 categories microsomal and non microsomal 1 】 Microsomal 2 】 Non Microsomal Enzymes MICROSOMAL : 1) Catalyze a majority of Drug Biotransformation reaction 2) A large variety of microsomal Enzymes Catalyze a number of oxidation reduction & hydrolytic & glucarunidation reaction IMPORTANT CHARACTER : * The impact nature of lipid memberane bound Enzymes of the microsomal is essential for it's selectively towards lipid soluble substance * A number of lipid soluble substance can interact non specifically with the microsomal Enzymes

6. NON MICROSOMAL ENZYMES : 1) Present in soluble from of the cytoplasm & those attached to the mitochondria but not the endoplasmic reticulum 2) Non specific that Catalyze few oxidation reaction hydrolytic reaction Nd Conjugation reaction other than Glucarunidation Example : Oxidases, perioxidases, dehydrogenase Esterase

7. FIRST PASS METABOLISM 1) This refers.to Metabolism of a drug during its passage from the site of adsorption into the systemic circulation. 2) All orally admistered drug are exposed to the drug Metabolism Enzymes in the esenssial wall liver 3) presystem Metabolism of limited magnitude can also occur in the skin and in Lungs . Attribute of Drug With High First pass Metabolism : * Oral dose is comsiderally higher than sublingual or parental dose * There is marked individual variation in the oral dose due to difference in the extent of First pass Metabolism * Oral bioavailability is apparently increase in patient with sever liver disease * Oral bioavailability of a drug is increase if another drug competing with it in First pass Metabolism is given concurrently Example : Chlorpromazine & Propranolol

8. PHASES OF DRUG METABOLISM R.T Williams divided the pathways of Metabolism reaction two genernal category phase 1 and phase 2 reaction . PHASE I : 1) Oxidation Reaction 2) Reduction Reaction 3) Hydrolytic Reaction A 】 OXIDATION REACTION : Oxidation reaction increase hydrophilicity of xenobiotics by introduction polar functional group such as -oH such a polar metabolites can thus rapidly undergoes phase II reaction or is excretable by the kidney . Oxidation of xenobiotics is nonspecifically catalysed by a number of Enzymes located in the micromes . RH +O + NADPH + H ------------> ROH + H2O + NADPH Since NADPH reduced NADP + * + + + 2

9. Cytochrome P-450 oxidase reduces Cycle

10. Others Oxidation Reaction : 1) Oxidation of aromatic carbon atom 2) Oxidation of olefinc (C=C) bonds. 3) Oxidation of benzylic allylic carbon atom 4) Oxidation of aliphatic carbon atom 5) Oxidation of alicyclic carbon atom B 】 REDUCTIVE REACTION : A number of reductive reaction are extract opposite to Oxidation Sum Reductive reaction are as follows : 1) Reduction of carbonyl function 2) Reduction of alcohol and C=C bonds 3) Reduction of N- compound

11. C 】 HYDROLYTIC REACTION : * These reaction differ from oxidation and Reductive reaction * The reaction does not involve change in the state of oxidation of the substance Sum Hydrolytic Reaction are as follows : 1) Hydrolysis of amides 2) Hydrolytic of ester and ethers 3) Hydrolytic cleavage of non aromatic heterocycles 4) Hydrolytic deologenation 5) Miscellaneous Hydrolytic Reaction

12. PHASE II : PHASE II : The two phase II reaction viz acetylation and methylation that do not generate polar product that do not generate polar product also termination the pharmacology activity of xenobiotics Thus ,phase II reaction are the real drug detoxication pathways Reaction involved in phase II Reaction : 1) Conjugation with glucuronic acid 2) Conjugation with sulfate moieties 3) Conjugation with alfa-amino acids 4) Conjugation with glutathione 5) Acetylation Reaction 6) Methylation Reaction 7) Miscellaneous Conjugation reaction

13. FACTORS AFFECTING DRUG METABOLISM : Physiochemical properties of the drug Chemical Factors a] Induction of Drug Metabolism Enzymes b] Induction of Drug Metabolism Enzymes C] Environmental chemical 3. Biological Factors a] Species Differences b] Strain Difference C] Sex difference d] Age e] Altered physiologic Factors F] Temporal Factors

14. REFERENCE 1] Tripathi K.D : Essentials of medical Pharmacology, Jaypee brothers, medical publishers , New delhi. 2] Barar F S.K.: Essential of pharmacotherapeutic, S.Chand & Co. ,New Delhi.

15. https://www.google.co.in/search?client=ms-android-xiaomi&biw=360&bih=269&tbm=isch&sa=1&ei=AfMBWq-tI52SvQSQ2J_gCA&q=organs+and+enzymes+involved+in+drug+metabolism+diagram&oq=organs+and+enzymes+involved+in+drug+metabolisum++diagram&gs_l=mobile-gws-img.1.0.30i10k1.4618.59451.0.60691.106.86.3.1.1.0.795.26241.0j9j41j19j8j4j2.83.0....0...1.1j4.64.mobile-gws-img..43.41.13337.3..0j41j0i67k1j0i5i30k1j0i24k1.0.ssKh0PWGjVM

16. REFERENCE

17. https://www.google.co.in/search?client=ms-android-xiaomi&biw=360&bih=269&tbm=isch&sa=1&ei=AfMBWq-tI52SvQSQ2J_gCA&q=organs+and+enzymes+involved+in+drug+metabolism+diagram&oq=organs+and+enzymes+involved+in+drug+metabolisum++diagram&gs_l=mobile-gws-img.1.0.30i10k1.4618.59451.0.60691.106.86.3.1.1.0.795.26241.0j9j41j19j8j4j2.83.0....0...1.1j4.64.mobile-gws-img..43.41.13337.3..0j41j0i67k1j0i5i30k1j0i24k1.0.ssKh0PWGjVM