Презентация на тему "Биотрансформации"

Содержание

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  BIOTRANSFORMATION

  3/7/2017 1 DR. NASIR ALI AFSAR

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  CLEARANCE OF DRUGS

  3/7/2017 2 Definition Why needed? Either Unchanged Metabolites Polarity of compounds

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  BIOTRANSFORMATION

  3/7/2017 3 Definition Sites Liver GIT Kidneys Others Lungs Skin

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  Phases

  3/7/2017 4 Phase I - Nonsynthetic make polar by unmasking a functional group like -OH, -NH2, -SH. oxidation-add O, remove H reduction-remove O, add H hydrolysis - add H2O Phase II - Synthetic make very polar Generally act in tandem

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  3/7/2017 5 Nonsynthetic or Phase I Reactions: Site

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  3/7/2017 6 Oxidation Reduction Hydrolysis hydroxylations aromatic, aliphatic, nitrogen dealkylations(N-, S-, P) deaminations N-, S-, P- oxidations S-replacements epoxidations others azo reduction nitro reduction disulfide reduction others esters amides oxidoreductases oxidases monoamine oxidases mixed function oxidases oxidoreductases reductases esterases amidases peptidases lipases Nonsynthetic or Phase I Reactions:

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  Nonsynthetic or Phase I Reactions: Cyt P450

  3/7/2017 7

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  3/7/2017 8 Nonsynthetic or Phase I Reactions: Cyt P450

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  3/7/2017 9 Nonsynthetic or Phase I Reactions: Cyt P450

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  Enzyme Induction

  3/7/2017 10 Enhance synthesis: Phenobarbital, Steroids Reduce rate of degradation: ‘Substrate Stabilization’ Clotrimazole, Ethanol

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  Enzyme Inhibition

  3/7/2017 11 Binding/Inactivation of heme iron: Imidazoles, Macrolides Inactivation of the enzyme protein: suicide inhibitors: Chloramphenicol combination of above: Secobarbital

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  Synthetic or Phase II Reactions:

  3/7/2017 12 Involves high energy intermediates Glucuronidation, Acetylation, Methylation, Glutathione/ Glycine/ Sulfate/ Water Conjugation. Transferases in microsomes or cytosol Role of nutrition in regulation of drug conjugation

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  3/7/2017 13 Results of Biotransformation Biotransformed Drug or Poison active inactive active inactive more potent TOXIC less potent In general - nonsynthetic reactions precede synthetic reactions can produce active metabolites synthetic reactions produce inactive metabolites Drug or Poison

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  Clinical Relevance

  3/7/2017 14 Individual Differences Age & Sex Genetic Factors Diet & Environmental factors Drug interactions Diseases

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  3/7/2017 15 THANK YOU REFERENCES Goodman & Gilman’s Pharmacological Basis of Therapeutics. Ed. 10 Pharmacology: by Range, Dale & Ritter. Ed. 4 Katzung’s Basic and Clinical Pharmacology. Ed. 8.