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Презентация на тему Biotransformation

12/22/2021CLEARANCE OF DRUGSDefinitionWhy needed?Either UnchangedMetabolitesPolarity of compounds
BIOTRANSFORMATIONDR. NASIR ALI AFSAR 12/22/2021CLEARANCE OF DRUGSDefinitionWhy needed?Either UnchangedMetabolitesPolarity of compounds 12/22/2021BIOTRANSFORMATIONDefinitionSitesLiverGITKidneysOthersLungsSkin 12/22/2021PhasesPhase I - Nonsyntheticmake polar by unmasking a functional group like -OH, 12/22/2021Nonsynthetic or Phase I Reactions: Site 12/22/2021	Oxidation			Reduction		Hydrolysishydroxylations	aromatic, aliphatic, nitrogendealkylations(N-, S-, P)deaminationsN-, S-, P- oxidationsS-replacementsepoxidationsothersazo reductionnitro reductiondisulfide reductionothersestersamidesoxidoreductasesoxidases 12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450 12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450 12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450 12/22/2021Enzyme InductionEnhance synthesis: Phenobarbital, SteroidsReduce rate of degradation: ‘Substrate Stabilization’Clotrimazole, Ethanol 12/22/2021Enzyme InhibitionBinding/Inactivation of heme iron: Imidazoles, MacrolidesInactivation of the enzyme protein: suicide inhibitors:Chloramphenicolcombination of above: Secobarbital 12/22/2021Synthetic or Phase II Reactions:Involves high energy intermediatesGlucuronidation, Acetylation, Methylation, Glutathione/ Glycine/ 12/22/2021Results of BiotransformationBiotransformed Drug or PoisonIn general -nonsynthetic reactionsprecede synthetic reactionscan produce 12/22/2021Clinical RelevanceIndividual DifferencesAge & SexGenetic FactorsDiet & Environmental factorsDrug interactionsDiseases 12/22/2021THANK  YOUREFERENCES 	Goodman & Gilman’s Pharmacological Basis of Therapeutics. Ed. 10
Слайды презентации

Слайд 2 12/22/2021
CLEARANCE OF DRUGS
Definition
Why needed?
Either
Unchanged
Metabolites
Polarity of compounds

12/22/2021CLEARANCE OF DRUGSDefinitionWhy needed?Either UnchangedMetabolitesPolarity of compounds

Слайд 3 12/22/2021
BIOTRANSFORMATION
Definition
Sites
Liver
GIT



Kidneys
Others
Lungs
Skin

12/22/2021BIOTRANSFORMATIONDefinitionSitesLiverGITKidneysOthersLungsSkin

Слайд 4 12/22/2021
Phases
Phase I - Nonsynthetic
make polar by unmasking a

12/22/2021PhasesPhase I - Nonsyntheticmake polar by unmasking a functional group like

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

Слайд 5 12/22/2021
Nonsynthetic or Phase I Reactions: Site

12/22/2021Nonsynthetic or Phase I Reactions: Site

Слайд 6 12/22/2021
Oxidation




Reduction



Hydrolysis
hydroxylations
aromatic, aliphatic, nitrogen
dealkylations(N-, S-, P)
deaminations
N-, S-, P- oxidations
S-replacements
epoxidations
others
azo

12/22/2021	Oxidation			Reduction		Hydrolysishydroxylations	aromatic, aliphatic, nitrogendealkylations(N-, S-, P)deaminationsN-, S-, P- oxidationsS-replacementsepoxidationsothersazo reductionnitro reductiondisulfide reductionothersestersamidesoxidoreductasesoxidases

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:


Слайд 7 12/22/2021
Nonsynthetic or Phase I Reactions: Cyt P450

12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450

Слайд 8 12/22/2021
Nonsynthetic or Phase I Reactions: Cyt P450

12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450

Слайд 9 12/22/2021
Nonsynthetic or Phase I Reactions: Cyt P450

12/22/2021Nonsynthetic or Phase I Reactions: Cyt P450

Слайд 10 12/22/2021
Enzyme Induction
Enhance synthesis:
Phenobarbital, Steroids
Reduce rate of degradation:

12/22/2021Enzyme InductionEnhance synthesis: Phenobarbital, SteroidsReduce rate of degradation: ‘Substrate Stabilization’Clotrimazole, Ethanol


‘Substrate Stabilization’
Clotrimazole, Ethanol


Слайд 11 12/22/2021
Enzyme Inhibition
Binding/Inactivation of heme iron:
Imidazoles, Macrolides
Inactivation of

12/22/2021Enzyme InhibitionBinding/Inactivation of heme iron: Imidazoles, MacrolidesInactivation of the enzyme protein: suicide inhibitors:Chloramphenicolcombination of above: Secobarbital

the enzyme protein: suicide inhibitors:
Chloramphenicol
combination of above:
Secobarbital


Слайд 12 12/22/2021
Synthetic or Phase II Reactions:
Involves high energy intermediates
Glucuronidation,

12/22/2021Synthetic or Phase II Reactions:Involves high energy intermediatesGlucuronidation, Acetylation, Methylation, Glutathione/

Acetylation, Methylation, Glutathione/ Glycine/ Sulfate/ Water Conjugation.
Transferases in microsomes

or cytosol
Role of nutrition in regulation of drug conjugation

Слайд 13 12/22/2021
Results of Biotransformation
Biotransformed Drug or Poison

In general -
nonsynthetic

12/22/2021Results of BiotransformationBiotransformed Drug or PoisonIn general -nonsynthetic reactionsprecede synthetic reactionscan

reactions
precede synthetic reactions
can produce active metabolites
synthetic reactions
produce inactive

metabolites

Drug or
Poison


Слайд 14 12/22/2021
Clinical Relevance
Individual Differences
Age & Sex
Genetic Factors
Diet & Environmental

12/22/2021Clinical RelevanceIndividual DifferencesAge & SexGenetic FactorsDiet & Environmental factorsDrug interactionsDiseases

factors
Drug interactions
Diseases


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