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drug metabolism- Biopharmaceutics

drug metabolism- Biopharmaceutics

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  • 1. WELCOME TO SEMINAR ONDRUG METABOLISM
  • 2. SEMINAR ON DRUG METABOLISM UNDER THE GUIDANCE OF K.SRIKANTH GUPTABY ASST.PROFESSORSAMEERA PRIPM-PHARMACY -1YR(PHARMACEUTICS) UNDER THE CO-GUIDANCE OF11CM1S0313 V.RAMA MOHAN GUPTAPRIP. PRINCIPAL & HOD PRIP
  • 3. CONTENTSINTRODUCTION TO METABOLISM 1 2 DRUG METABOLISM INTRODUCTION 3 SITES OF DRUG METABOLISM4 METHODS FOR STUDY OF DRUG METABOLISM56
  • 4. INTRODUCTION TO METABOLISMSum total of all the enzyme –catalyzed reactions that occur in an organism.
  • 5. METABOLIC PATHWAYS
  • 6. TYPES OF METABOLISM
  • 7. IMPORTANCE OF METABOLISM To obtain chemical energy To synthesize complex molecules To convert nutrient molecule into its precursor form for future use
  • 8. •What is drug metabolism?•Importance of drug metabolism? Why it isnecessary?•How it will takes place?•Where it will takes place?(sites of drug metabolism)•When it will takes place ?
  • 9. 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
  • 10.  Termination of drug action .Activation of prodrug .Bioactivation and toxication .Carcinogenesis Tetratogenesis
  • 11. 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 
  • 12.  Inactive active parent compound metaboliteEg: Levodopa dopamine
  • 13. Some Xenobiotics Are Metabolized to Carcinogenic Agents• 3,4 Benzopyrene• Aflatoxin• N-Acetylaminofluorene Metabolites of these agents interact with DNA
  • 14. Small Amounts of Acetaminophen is Converted to the Reactive Metabolite N-Acetyl benzo quinone imine bioactivationBioactivation of acetaminophen; under certain conditions, the electrophile N-acetyl benzo quinone imine reacts with tissue macromolecules, causing liver necrosis
  • 15. Some drugs that produce active or toxic metaboliteInactive drugs Active metabolite:(Pro-drugs)Cyclophophamide Phosphoramide musrardPrednisone prednisoloneActive drug Active metaboliteAmitriptyline NortriptylineDiazepam OxazepamActive drug Toxic metaboliteHalothane Trifluoroacetic acidParacetamol N-acetyl-p-benzo-quinone-imine
  • 16. 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
  • 17. 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
  • 18. CELLULAR SITES OF DRUG METABOLISMCytosol MitochondriaLysosomesSmooth endoplasmic reticulum (microsomes)
  • 19. Phases of drug metabolism
  • 20. 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
  • 21. DRUG METABOLISING ENZYMESMicrosomal enzymesNon microsomal enzymes
  • 22. METHODS FOR THE STUDY OF DRUG METABOLISM 1. 2.
  • 23. METhODS USED In STUDy OF METABOLISM
  • 24. FACTORS AFFECTING DRUG METABOLISM
  • 25. physico chemical properteis of drug:
  • 26. chemical factors:
  • 27. ENZYME INDUCTION8 ENZYME INDUCTION 8• Enzyme Induction - increased enzyme protein levels in thecell •Phenobarbital type induction by many drugs •Polycyclic hydrocarbon type induction by polycyclic hydrocarbons such as 3,4-benzopyrene and 3- methylcholanthrene
  • 28. CORRELATION BETWEEN SLEEPING TIME AND PLASMAT1/2 IN CHRONIC PENTOBARBITAL PRETREATED RABBITS
  • 29. 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
  • 30. 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
  • 31. Enzyme inhibition Product metabolism Repression
  • 32. 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
  • 33. 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
  • 34. Enzyme inhibitors &drugs affected by themInhibitor Drugs affectedMAO Barbiturates,TyramineCoumarins PhenytoinAllopurinol 6-mercaptopurinPAS Phenytoin Hexobarbitol
  • 35. ENVIRONMENTAL CHEMICALSDDTPolycyclic aromatic hydrocarbons-enzyme induction effectOrgano phosphate insecticidesHeavy metals-Mercury,Cobalt,Arsenic(enzyme inhibition effect)TemperatureAtmospheric pressure
  • 36. SPECIES VARIATION
  • 37. Ethnic variations in the N-Acetylation of IsoniazidEthnic group % of slow % of rapid acetylators acetylatorsWhiters 45 55(USA,Canada)Blacks(USA) 48 52Latin Americans 67 33American Indians 79 21Japanes 87 13Eskimos 98 05
  • 38. AGENeonatesChildrenElderly
  • 39. 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)
  • 40. State of health Hepatitis Liver cancer Cardiac insufficiency
  • 41. 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
  • 42. 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?
  • 43. REFERENCES SATYANARAYANA BIOCHEMISTRY J.L.JAIN FUNDAMENTALS OF BIOCHEMISTRY HERPER’S BIOCHEMISTRY MARTIN’S 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