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Pharmacokinetics

QuestionAnswer
Km [S] at Vmax, low Km => high affinity
Noncompetitive inhibitor -Does not resemble substrate -Does not bind to active site -Cannot be overcome by increased [S] -Decreases Vmax, no effect on Km -Decreases efficacy of substrate
Competitive inhibitor -Resembles substrate -Binds to active site -Can be overcome by increased [S] -Decreases Km, no effect on Vmax -Decreases potency of substrate
Volume of Distribution (Vd) = (Amount of drug in body)/(Concentration of drug in plasma) Low Vd => distributes in blood Med Vd => distributes in extracellular space/body water High Vd => distributes in tissues
Clearance = (rate of elimination)/(plasma concentration) = Vd x Ke
Loading dose = Cp x Vd/F Not affected by renal/hepatic dysfunction
Maintenance dose = Cp x Cl/F Decreased by renal/hepatic dysfunction
Zero-order elimination Constant amount of drug eliminated over time, regardless of concentration Phenytoin, Ethanol, Aspirin
First-order elimination Elimination rate proportional to concentration, constant fraction of drug eliminated per unit time (exponential decay)
Weak acids Trapped in basic environments, treat overdose w/ bicarb Phenobarbitol, MTX, TCAs, aspirin HB + OH- --> B- + H2O
Weak bases Trapped in acidic environment, treat overdose w/ ammonium chloride Amphetamines BOH + H+ --> B+ + H2O
Phase I metabolism Reduction, oxidation, hydrolysis Yields slightly polar, water-soluble metabolites, often still active CyP450 Lost first by elderly patients
Phase II metabolism Acetylation, glucuronidation, sulfation Yields very polar, inactive metabolites for renal excretion Conjugation, separate from P450
Therapeutic index = median LD50/median ED50
Created by: zacharykr
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