Block I - Kinetics - M Flashcards
How liver metabolizes drug
Oral drug -> stomach/GI -> hepatic portal system (liver) -> systemic circulation. Reduced amount of active drug (decreased bioavailability) due to: metabolism (phase I and phase II CYP450 modify drugs to be more polar for increase excretion), intestinal/biliary excretion (decreased bioavailability in intestine/bile, respectively).
Prodrug
Needs to be metabolically activated by CYP450.
Metabolite (inactive, active, toxic)
CYP metabolism causes drug to be: inactive - produce no biological action, active - produces biological action, toxic - conversion of drug into form that is toxic
Phase 1 reaction
Increase drugs polarity for increased excretion.
Phase 2 reaction
Conjugation: make more polar and hydrophilic to be excreted.
Induction
Increase enzymes needed to metabolize drugs (lowers plasma conc of drug = lower effect of drugs).
Inhibition
Decrease activity of drug metabolism (highter plasma conc of drug = potentially dangerous for pt).
CYP450 function
Acts to catalyze phase 1 reactions by adding polar groups to drug for increased elimination by kidney.
Inhibiting CYP450, et al
Grapefruit juice inhibits CYP34A, increases plasma conc of simvastatin = increased drug effect
Inducing CYP450, et al
Increase CYP450 isozyme leading to increased biotransformation = higher metabolism = lower plasma conc = decreased drug effect.
Liver function and CYP450
Decreased liver function is the equivalent of inhibiting CYP450. Giving pt inhibitors will further decrease ability for liver to metabolize drugs.
Conjugation and helping elimination
After phase 1, drug may be too lipophilic and retained by kidney tubules. Conjugation (phase 2) makes compound more polar and hydrophilic allowing drug to be excreted by kidney or in bile.
