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VetMed Pharmacology4

VetMed Pharmacology - Metabolism

Importance of Pharm Metabolism influences plasma drug concentrations facilitates improved excretion has a protective effect influence efficacy and side effects influenced by co-administration of multiple pharms influenced by disease
Goals of Pharm Metabolism pharmaceutical inactivation enhanced pharm excretion convert "pro-drugs" to a biologically active form metabolized to a highly toxic metabolite(s)
Biotransformation Variables species breed sex, repro status genetics stress and physiology diet age disease processes weight time of day hormonal/endocrine status absorption (PO vs. IV) induction of metabolism pathways by exogenous pharms or toxins inhibition of biochem
Objective of Phase I Metabolism small chemical groups associated with a given pharm are biochemically transformed into a more polar form that increases their aqueous solubility
Effects of Phase I Metabolism decreases pharm bio activity decreases volume of distribution enhances probability of being excreted creates chemical "handles" for Phase II
Types of Phase I Non-Synthetic Biotransformation Reactions P450-dependent oxidation reactions P450 independent oxidation reactions Non-microsomal oxidation reactions Reduction reactions Hydrolysis reactions
Microsomal Mixed-Function Oxidases the major enzyme systems responsible for pharm metabolization
P450 Independent Hydrolysis Reaction common metabolic pathway for esters and amines
Phase II Metabolism not required Phase I metabolite is synthetically conjugated to a relatively large MW moiety
Effects of Phase II Metabolism increases MW which increases aqueous solubility increases polarity which increases aqueous solubility inactivates "parent" pharm
Results of Phase II Metabolism decreased distribution of synthetic metabolites throughout body decreased passive diffusion across biliary tree decreased passive diffusion out of urinary filtrate
Glucuronidation most common Phase II conjugation reaction
Glucuronyl Transferase enzyme involved in glucuronidation deficient in cats, mammalian fetuses, early-age neonates
Anatomical Locations of Phase I Metabolism Reactions liver (primary) kidney lung
"Pro-drug" Metabolism pharm given is inactive and then metabolized to a biologically active form
Toxic Metabolite the metabolite is more toxic than the parent pharm
Induction of Cytochrome P450 Enzyme phenobarbital increases activity of cP450, thus increasing the rate of metabolism of the substrate (i.e. Warfarin)
Microsomal Mixed-Function Enzyme Systems only class of enzyme systems that can be induced
Created by: 26509889