Module 1 ADME (ME) Flashcards
drug metabolism transformations
active drug -> inactive drug
active druge -> active metabolite
active drug -> toxic metabolite
prodrug -> active drug (uses metabolism to activate)
unexcretable drug -> excretable metabolite
organs of metabolism
liver kidneys GI tract lungs skin other
metabolism
- drugs must be unbound in plasma
- generation of polar and/or hydrophilic inactive metabolites (excretable)
- Biotransformation reactions
biotransformation reactions
phase 1: oxidation/reduction
phase 2: conjugation/hydrolysis
Phase 1 biotransformation CYP450
95% of all oxidative reactions 75% of all drugs addition of hydroxyl group to drug - rapid excretion into urine - if not excreted goes to phase 2
CYP450
enzyme family-subfamily- specific enzyme
- substrate specificity: specific to certain drugs for breakdown
phase 1 alcohol dehydrogenase
oxidized alcohols to aldehyde derivatives
phase 1 and MAO
oxidized amines
phase 2 biotransformation
results in large polar conjugates
- rapidly excreted in urine or feces
CYP450 induction
increased transcription or translation
dec. degradation
induction by another drug or autoinduction
- increases metabolism
CYP450 inhibition
incidental or deliberate
competitive inhibition
irreversible inhibition
irreversible inhibition
body must create more enzymes to metabolize drug and excrete
factors affecting metabolism
genetics - slow or fast acetylator Race/ethnicity Age and gender diet - grapefruit disease states - liver disease, cardiac disease
excretion
either unchanged or as metabolites
organs:
- lungs: polar compounds, anes. drugs
- renal: glomerular filtration, active tubular secretion
- feces: unabsorbed orally admin. drugs, or drugs excreted via bile
