PHARMACOKINETICS 3 Flashcards
Include oxidation (especially by the cytochrome P45- group of enzymes also called mixed function oxidases), reduction, deamination and hydrolysis
Phase 1 metabolism
Refers to the loss of electrons, and an increase in oxidation state
Oxidation
Involves cytochrome P-450 mixed oxidase system
CYP-mediated
Refers to the addition of electrons and a decrease of oxidation state
Reduction
It involves splitting of large molecule involving water as solvent
Hydrolysis
Synthetic reactions that involve addition (conjugation) of subgroups to -OH, -NH 2, and -SH functions on the drug molecule.
Phase 2 Metabolism
(T/F) Phase 2 Metabolism convert the Phase I metabolites to more polar and water-soluble
products
True
The condensation of the drug or its primary metabolite with d-glucoronic acid
GLUCURONIDATION
(T/F) The human newborn is still not capable of sulfate conjugation
False (Capable)
It is the most common endogenous amine for conjugation with organic acids.
Glycine
(T/F) A newborn is not capable of acetylation.
True
It is only a minor pathway for conjugating drugs and xenobiotics
METHYLATION
Parts of Phase 1 Metabolism
Oxidation
Reduction
Hydrolysis
Phase II: GLUCORONIC ACID CONJUGATION Enzyme
GLUCORONOSYL TRANSFERASE
Phase II: SULFATE CONJUGATION Enzyme
SULFOTRANSFERASES
Phase II: GLUTATHIONE CONJUGATION Enzyme
GLUTATHIONE-S-TRANSFERASE
Phase II: ACETYLATION Enzyme
N-ACETYL TRANSFERASES
Phase II: METHYLATION Enzyme
METHYL TRANSFERASE
Phase II: Amino Acid Conjugation Enzyme
COENZYME A
(T/F) Alteration in the enzyme activity in liver microsomes resulting in a faster rate of metabolism
True
A drug that stimulates its own metabolism
AUTO-INDUCTION (Phenobarbital)
Induction where one enzyme inducer stimulate the rate of metabolism of another drug
FOREIGN-INDUCTION
May be due to substrate competition or due to direct inhibition of drug metabolizing enzyme
ENZYME INHIBITION
The final elimination of the drug substance
Excretion
Primary site of excretion
Kidney
Part of the kidney that is responsible for the removal of metabolic waste and the maintenance of water and electrolyte balance
Nephrons
Normal GFR
125mL/min (180 L/day
General term that incorporates all the
processes that may be involved in removing
a parent drug from the body
Drug Elimination
Collectively, they are responsible for the
elimination of over 90% of drugs
Renal excretion and metabolism
Involved in the elimination of less than 10%
of parent drugs.
Excretion of the parent drug into the bile
