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Drug metabolism ppt

Sameera Sam
Sameera Sam

The document provides an overview of drug metabolism. It discusses that drug metabolism is important as it converts lipophilic drugs to hydrophilic metabolites that can be readily excreted. The key sites of drug metabolism are the liver, GI tract, lungs and kidneys. Metabolism occurs via phase I and phase II reactions and can activate or deactivate drugs. Factors like enzymes, diet, disease and genetics influence an individual's metabolism. Understanding metabolism is important for drug efficacy, toxicity and interactions.

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WELCOME TO SEMINAR ON DRUG METABOLISM
SEMINAR ON DRUG METABOLISM UNDER THE GUIDANCE OF K.SRIKANTH GUPTA BY ASST.PROFESSOR SAMEERA PRIP M-PHARMACY -1YR (PHARMACEUTICS) UNDER THE CO-GUIDANCE OF 11CM1S0313 V.RAMA MOHAN GUPTA PRIP. PRINCIPAL & HOD PRIP
CONTENTS INTRODUCTION TO METABOLISM 1 2 DRUG METABOLISM INTRODUCTION 3 SITES OF DRUG METABOLISM 4 METHODS FOR STUDY OF DRUG METABOLISM 5 6
Drug metabolism ppt
INTRODUCTION TO METABOLISM Sum total of all the enzyme catalyzed reactions that occur in an organism.
METABOLIC PATHWAYS
TYPES OF METABOLISM
IMPORTANCE OF METABOLISM To obtain chemical energy To synthesize complex molecules To convert nutrient molecule into its precursor form for future use
Drug metabolism ppt
What is drug metabolism? Importance of drug metabolism? Why it is necessary? How it will takes place? Where it will takes place?(sites of drug metabolism) When it will takes place ?
WHY DRUG METABOLISM IMPORTANT? Drugs are mostly lipid soluble, easy to cross membranes, bind to plasma proteins & reabsorb from renal tubules Metabolism changes them to water soluble & easily excretable products; also become inactive or less active
Termination of drug action .Activation of prodrug .Bioactivation and toxication .Carcinogenesis Tetratogenesis
Termination of Drug Action Conversion of drug to active metabolite to active metabolite to inactive metabolite Parent compound inactive metabolite Atropine tropic acid & tropin propranolol hydroxyl propranolol
Inactive active parent compound metabolite Eg: Levodopa dopamine
Some Xenobiotics Are Metabolized to Carcinogenic Agents 3,4 Benzopyrene Aflatoxin N-Acetylaminofluorene Metabolites of these agents interact with DNA
Small Amounts of Acetaminophen is Converted to the Reactive Metabolite N-Acetyl benzo quinone imine bioactivation Bioactivation of acetaminophen; under certain conditions, the electrophile N-acetyl benzo quinone imine reacts with tissue macromolecules, causing liver necrosis
Some drugs that produce active or toxic metabolite Inactive drugs Active metabolite: (Pro-drugs) Cyclophophamide Phosphoramide musrard Prednisone prednisolone Active drug Active metabolite Amitriptyline Nortriptyline Diazepam Oxazepam Active drug Toxic metabolite Halothane Trifluoroacetic acid Paracetamol N-acetyl-p-benzo-quinone-imine
Thalidomide is a Teratogen (teratogenesis) THALIDOMIDE: Fetal malformations in humans, monkeys, and rats occur due to metabolism of the parent compound to a teratogen. This occurs very early in gestation
Drug metabolism ppt
Sites of drug metabolism Liver is the principal organ of drug metabolism Other sites are GI mucosa, lungs, skin and kidneys Every tissue has some ability to metabolize drugs Some drugs, after oral administration (clonazepam & propranolol) are extensively metabolized in GI or liver, before reaching systemic circulation or sit of action, called 1st pass effect, it reduces their bioavailability In the liver cells metabolic enzymes are located in the smooth microsomes of endoplasmic reticulum
CELLULAR SITES OF DRUG METABOLISM Cytosol Mitochondria Lysosomes Smooth endoplasmic reticulum (microsomes)
Phases of drug metabolism
Phases of drug metabolism(cont) Drug metabolism can be categorized to: Phase-I reactions: oxidations, reductions & hydrolysis Phase-II reactions: conjugations Glucuronide conjugation Aspirin Salicylic acid COOH COOH COOH OCOCH3 OH OH O OH HO Phase-I Phase-II O COOH
DRUG METABOLISING ENZYMES Microsomal enzymes Non microsomal enzymes
METHODS FOR THE STUDY OF DRUG METABOLISM 1. 2.
METhODS USED In STUDy OF METABOLISM
Drug metabolism ppt
FACTORS AFFECTING DRUG METABOLISM
physico chemical properteis of drug:
chemical factors:
ENZYME INDUCTION8 ENZYME INDUCTION 8 Enzyme Induction - increased enzyme protein levels in the cell Phenobarbital type induction by many drugs Polycyclic hydrocarbon type induction by polycyclic hydrocarbons such as 3,4-benzopyrene and 3- methylcholanthrene
Drug metabolism ppt
CORRELATION BETWEEN SLEEPING TIME AND PLASMA T1/2 IN CHRONIC PENTOBARBITAL PRETREATED RABBITS
Consequences of Induction Increased rate of metabolism Decrease in drug plasma concentration Enhanced oral first pass metabolism Reduced bioavailability If metabolite is active or reactive, increased drug effects or toxicity
Therapeutic Implications of Induction Most drugs can exhibit decreased efficacy due to rapid metabolism but drugs with active metabolites can display increased drug effect and/or toxicity due to enzyme induction Dosing rates may need to be increased to maintain effective plasma concentrations
Enzyme inhibition Product metabolism Repression
Consequences of Inhibition Increase in the plasma concentration of parent drug Reduction in metabolite concentration Exaggerated and prolonged pharmacological effects Increased liklihood of drug-induced toxicity
Therapeutic implications of Inhibition May occur rapidly with no warning Particularly effects drug prescribing for patients on multidrug regimens Knowledge of the CYP450 metabolic pathway provides basis for predicting and understanding inhibition Esp drug drug interaction
Enzyme inhibitors &drugs affected by them Inhibitor Drugs affected MAO Barbiturates,Tyramine Coumarins Phenytoin Allopurinol 6-mercaptopurin PAS Phenytoin Hexobarbitol
ENVIRONMENTAL CHEMICALS DDT Polycyclic aromatic hydrocarbons-enzyme induction effect Organo phosphate insecticides Heavy metals-Mercury,Cobalt,Arsenic(enzyme inhibition effect) Temperature Atmospheric pressure
SPECIES VARIATION
Ethnic variations in the N-Acetylation of Isoniazid Ethnic group % of slow % of rapid acetylators acetylators Whiters 45 55 (USA,Canada) Blacks(USA) 48 52 Latin Americans 67 33 American Indians 79 21 Japanes 87 13 Eskimos 98 05
AGE Neonates Children Elderly
DIET Charcoal broiled foods (contain polycyclic hydrocarbons that increase certain enzyme protein in cells) Grapefruit juice (the active component is the furancoumarin 6,7-dihydroxybergamottin which inhibits a certain a group of microsomal enzymes)
State of health Hepatitis Liver cancer Cardiac insufficiency
CONCLUSION: Final conclusion of this study is enzymes will play a major role In drug metabolism especially cyp 450 .Lack of these enzymes will sometimes makes the drug low efficient
CASE STUDY A37-year-old woman visited her dentist for removal of her wisdom teeth. The teeth were found to be impacted, and removal necessitated extensive surgery. Following completion of the procedure on one side of the mouth, the patient was given a prescription for acetaminophen 300 mg with codeine 30 mg (combination product) for the relief of pain. The patient took the prescription as prescribed for approximately 2 days, but little pain relief was achieved. She called the dentist to get a prescription for another analgesic. What is a possible explanation for this lack of efficacy?
Drug metabolism ppt
REFERENCES SATYANARAYANA BIOCHEMISTRY J.L.JAIN FUNDAMENTALS OF BIOCHEMISTRY HERPERS BIOCHEMISTRY MARTINS PHYSICAL PHARMACY INTERNET BRAHMANKER-BIOPHARMACEUTICS VENKATESHWARLU-BIOPHARMACEUTICS http://www.hospitalist.net/highligh.htm DR.A.V.S.S.RAMA RAO A TEXT BOOK OF BIOCHEMISTRY LIPPINCOTT-MODERN PHARMACOLOGY WITH CLINICAL APPLICATIONS GOODMAN GILMAN-PRINCIPLES OF PHARMACOLOGY
Drug metabolism ppt
Drug metabolism ppt

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Drug metabolism ppt

  • 1. WELCOME TO SEMINAR ON DRUG METABOLISM
  • 2. SEMINAR ON DRUG METABOLISM UNDER THE GUIDANCE OF K.SRIKANTH GUPTA BY ASST.PROFESSOR SAMEERA PRIP M-PHARMACY -1YR (PHARMACEUTICS) UNDER THE CO-GUIDANCE OF 11CM1S0313 V.RAMA MOHAN GUPTA PRIP. PRINCIPAL & HOD PRIP
  • 3. CONTENTS INTRODUCTION TO METABOLISM 1 2 DRUG METABOLISM INTRODUCTION 3 SITES OF DRUG METABOLISM 4 METHODS FOR STUDY OF DRUG METABOLISM 5 6
  • 5. INTRODUCTION TO METABOLISM Sum total of all the enzyme catalyzed reactions that occur in an organism.
  • 8. IMPORTANCE OF METABOLISM To obtain chemical energy To synthesize complex molecules To convert nutrient molecule into its precursor form for future use
  • 10. What is drug metabolism? Importance of drug metabolism? Why it is necessary? How it will takes place? Where it will takes place?(sites of drug metabolism) When it will takes place ?
  • 11. WHY DRUG METABOLISM IMPORTANT? Drugs are mostly lipid soluble, easy to cross membranes, bind to plasma proteins & reabsorb from renal tubules Metabolism changes them to water soluble & easily excretable products; also become inactive or less active
  • 12. Termination of drug action .Activation of prodrug .Bioactivation and toxication .Carcinogenesis Tetratogenesis
  • 13. Termination of Drug Action Conversion of drug to active metabolite to active metabolite to inactive metabolite Parent compound inactive metabolite Atropine tropic acid & tropin propranolol hydroxyl propranolol
  • 14. Inactive active parent compound metabolite Eg: Levodopa dopamine
  • 15. Some Xenobiotics Are Metabolized to Carcinogenic Agents 3,4 Benzopyrene Aflatoxin N-Acetylaminofluorene Metabolites of these agents interact with DNA
  • 16. Small Amounts of Acetaminophen is Converted to the Reactive Metabolite N-Acetyl benzo quinone imine bioactivation Bioactivation of acetaminophen; under certain conditions, the electrophile N-acetyl benzo quinone imine reacts with tissue macromolecules, causing liver necrosis
  • 17. Some drugs that produce active or toxic metabolite Inactive drugs Active metabolite: (Pro-drugs) Cyclophophamide Phosphoramide musrard Prednisone prednisolone Active drug Active metabolite Amitriptyline Nortriptyline Diazepam Oxazepam Active drug Toxic metabolite Halothane Trifluoroacetic acid Paracetamol N-acetyl-p-benzo-quinone-imine
  • 18. Thalidomide is a Teratogen (teratogenesis) THALIDOMIDE: Fetal malformations in humans, monkeys, and rats occur due to metabolism of the parent compound to a teratogen. This occurs very early in gestation
  • 20. Sites of drug metabolism Liver is the principal organ of drug metabolism Other sites are GI mucosa, lungs, skin and kidneys Every tissue has some ability to metabolize drugs Some drugs, after oral administration (clonazepam & propranolol) are extensively metabolized in GI or liver, before reaching systemic circulation or sit of action, called 1st pass effect, it reduces their bioavailability In the liver cells metabolic enzymes are located in the smooth microsomes of endoplasmic reticulum
  • 21. CELLULAR SITES OF DRUG METABOLISM Cytosol Mitochondria Lysosomes Smooth endoplasmic reticulum (microsomes)
  • 22. Phases of drug metabolism
  • 23. Phases of drug metabolism(cont) Drug metabolism can be categorized to: Phase-I reactions: oxidations, reductions & hydrolysis Phase-II reactions: conjugations Glucuronide conjugation Aspirin Salicylic acid COOH COOH COOH OCOCH3 OH OH O OH HO Phase-I Phase-II O COOH
  • 24. DRUG METABOLISING ENZYMES Microsomal enzymes Non microsomal enzymes
  • 25. METHODS FOR THE STUDY OF DRUG METABOLISM 1. 2.
  • 26. METhODS USED In STUDy OF METABOLISM
  • 31. ENZYME INDUCTION8 ENZYME INDUCTION 8 Enzyme Induction - increased enzyme protein levels in the cell Phenobarbital type induction by many drugs Polycyclic hydrocarbon type induction by polycyclic hydrocarbons such as 3,4-benzopyrene and 3- methylcholanthrene
  • 33. CORRELATION BETWEEN SLEEPING TIME AND PLASMA T1/2 IN CHRONIC PENTOBARBITAL PRETREATED RABBITS
  • 34. Consequences of Induction Increased rate of metabolism Decrease in drug plasma concentration Enhanced oral first pass metabolism Reduced bioavailability If metabolite is active or reactive, increased drug effects or toxicity
  • 35. Therapeutic Implications of Induction Most drugs can exhibit decreased efficacy due to rapid metabolism but drugs with active metabolites can display increased drug effect and/or toxicity due to enzyme induction Dosing rates may need to be increased to maintain effective plasma concentrations
  • 36. Enzyme inhibition Product metabolism Repression
  • 37. Consequences of Inhibition Increase in the plasma concentration of parent drug Reduction in metabolite concentration Exaggerated and prolonged pharmacological effects Increased liklihood of drug-induced toxicity
  • 38. Therapeutic implications of Inhibition May occur rapidly with no warning Particularly effects drug prescribing for patients on multidrug regimens Knowledge of the CYP450 metabolic pathway provides basis for predicting and understanding inhibition Esp drug drug interaction
  • 39. Enzyme inhibitors &drugs affected by them Inhibitor Drugs affected MAO Barbiturates,Tyramine Coumarins Phenytoin Allopurinol 6-mercaptopurin PAS Phenytoin Hexobarbitol
  • 40. ENVIRONMENTAL CHEMICALS DDT Polycyclic aromatic hydrocarbons-enzyme induction effect Organo phosphate insecticides Heavy metals-Mercury,Cobalt,Arsenic(enzyme inhibition effect) Temperature Atmospheric pressure
  • 42. Ethnic variations in the N-Acetylation of Isoniazid Ethnic group % of slow % of rapid acetylators acetylators Whiters 45 55 (USA,Canada) Blacks(USA) 48 52 Latin Americans 67 33 American Indians 79 21 Japanes 87 13 Eskimos 98 05
  • 44. DIET Charcoal broiled foods (contain polycyclic hydrocarbons that increase certain enzyme protein in cells) Grapefruit juice (the active component is the furancoumarin 6,7-dihydroxybergamottin which inhibits a certain a group of microsomal enzymes)
  • 45. State of health Hepatitis Liver cancer Cardiac insufficiency
  • 46. CONCLUSION: Final conclusion of this study is enzymes will play a major role In drug metabolism especially cyp 450 .Lack of these enzymes will sometimes makes the drug low efficient
  • 47. CASE STUDY A37-year-old woman visited her dentist for removal of her wisdom teeth. The teeth were found to be impacted, and removal necessitated extensive surgery. Following completion of the procedure on one side of the mouth, the patient was given a prescription for acetaminophen 300 mg with codeine 30 mg (combination product) for the relief of pain. The patient took the prescription as prescribed for approximately 2 days, but little pain relief was achieved. She called the dentist to get a prescription for another analgesic. What is a possible explanation for this lack of efficacy?
  • 49. REFERENCES SATYANARAYANA BIOCHEMISTRY J.L.JAIN FUNDAMENTALS OF BIOCHEMISTRY HERPERS BIOCHEMISTRY MARTINS PHYSICAL PHARMACY INTERNET BRAHMANKER-BIOPHARMACEUTICS VENKATESHWARLU-BIOPHARMACEUTICS http://www.hospitalist.net/highligh.htm DR.A.V.S.S.RAMA RAO A TEXT BOOK OF BIOCHEMISTRY LIPPINCOTT-MODERN PHARMACOLOGY WITH CLINICAL APPLICATIONS GOODMAN GILMAN-PRINCIPLES OF PHARMACOLOGY