Unit 1- Metabolism Flashcards
What happens without metabolism?
Absorbed compounds retained longer, prolonged drug activity, tissue drug accumulation, potential toxicity
Major organ for drug transformation
Hepatic biotransformation and biliary excretion
Factors affecting liver metabolism
Biological properties and enzymes present, hepatic perfusion, drug accessibility to hepatic metabolic sites, physiochemical properties of the drug
Phase I Hepatic Metabolism
Makes lipid soluble drugs more water soluble, can inactivate, activate, or change toxicity
Phase II Hepatic Metabolism
Inactivates drugs
Other metabolic organs
Kidney, lungs, skin, GI
Cytochrome P450 Enzymes
Located in smooth ER, adds oxygen onto the substrate
Oxidation
Addition of oxygen across a double bond or to a carbon chain, causing loss of an electron
Hydrolysis
Splitting a drug molecule and adding water molecules
Reduction
Adding a hydrogen, gaining an electron
Prodrug
Inactive form of a drug that is activated
Glucoronidation
Addition of glucoronide conjugates that makes molecules water soluble
Polymorphisms in CYP
Extremely rapid metabolism of a drug or toxic effects from decreased metabolism
Cat Phase II Metabolism
Low concentrations of glucoronyl transferases prolongs clearance of drugs
Cat Phase I Metabolism
Deficiency in phase I demethylation and hydroxylation
Acetamenophan in Cats
Excess shunted back to phase I metabolism, producing oxygen radicals that cause liver and RBC damage
Sulfate Conjugating System
Alternative pathway to glucoronylation
Acetylation
Less common route of xenobiotics, deficiency in dogs can change dosing of parent drugs
Factors affecting metabolism
Activity of enzymes, hepatic blood flow, species, age, nutrition, tissue storage, health
Flavonoids
Found in grapefruit, inhibits CYP in small intestine
Ginkgo biloba
Induces CYP
Young animal metabolism
Lower oxidative enzymes, liver enzymes developed at 3 months
Hyperthyroid metabolism
Increased metabolic rate
Hypothyroid metabolism
Decreased drug metabolism
Drug interactions
Expect interactions when introducing multiple drugs metabolized by the liver
CYP Induction
Protective mechanism that facilitates excretion of toxic compounds, however toxic metabolites will accumulate in the liver
Type of Inhibitors
Reversible, quasireversible, and irreversible
Drug induced metabolism inhibition
Can decrease dosage needed and prevent metabolism to toxic metabolites
