Pharmaceutical Chemistry and Pharmacology Flashcards

A pharmacist is asked about the mechanism of vancomycin. How does vancomycin inhibit bacterial cell wall synthesis?

Answer: Binds D-Ala-D-Ala terminus of peptidoglycan precursors, preventing transglycosylation and transpeptidation

Vancomycin binds the D-Ala-D-Ala terminus of the lipid II peptidoglycan precursor, sterically blocking both transglycosylase and transpeptidase reactions. This prevents cross-linking of the peptidoglycan cell wall. VRE resistance arises from substituting D-Lac for D-Ala, reducing vancomycin binding affinity 1,000-fold.

Which pharmacological property determines if a drug will be excreted in the urine as the parent compound or as metabolites?

Answer: Lipophilicity and extent of hepatic metabolism — hydrophilic drugs are excreted unchanged; lipophilic drugs require metabolic conversion

Lipophilic drugs are extensively metabolized in the liver (phase I and II reactions) to more hydrophilic metabolites before renal/biliary excretion. Hydrophilic drugs are filtered by the glomerulus or secreted by transporters and excreted largely unchanged. This determines the need for dose adjustment in hepatic vs. renal failure.

A pharmacist reviews a patient's medication for potential QT prolongation risk. Which combination creates the highest risk for torsades de pointes?

Answer: Amiodarone + azithromycin + hypokalemia

QT prolongation risk is additive with multiple QT-prolonging drugs. Amiodarone (class III antiarrhythmic) + azithromycin (macrolide) combined with hypokalemia (which prolongs QT) represents extremely high torsades risk. Torsades de pointes can degenerate into ventricular fibrillation.

A patient develops increased phenytoin toxicity after starting isoniazid. What is the pharmacokinetic mechanism?

Answer: Isoniazid inhibits CYP2C9, reducing phenytoin metabolism and increasing phenytoin levels

Isoniazid is a CYP2C9 (and CYP2C19) inhibitor. Since phenytoin is primarily metabolized by CYP2C9, isoniazid inhibition reduces phenytoin clearance, causing drug accumulation and toxicity (nystagmus, ataxia, diplopia). This is a clinically significant TB/epilepsy co-treatment interaction.

What is the volume of distribution (Vd) and what does a very large Vd indicate?

Answer: Vd = dose / plasma concentration at time 0; large Vd indicates extensive tissue distribution and low plasma levels

Vd = Dose / C0 (plasma concentration at time 0). A large Vd (>1 L/kg) indicates the drug distributes extensively into tissues, with relatively little remaining in plasma. Drugs with large Vd (e.g., chloroquine, amiodarone) are not readily dialyzed. Small Vd drugs remain mostly in blood.

A pharmacist is explaining prodrugs. Codeine is a prodrug — what active metabolite is responsible for its analgesic effect?

Answer: Morphine — via CYP2D6 O-demethylation

Codeine is O-demethylated by CYP2D6 to morphine, which is responsible for the analgesic (and respiratory depressant) effect. Poor metabolizers of CYP2D6 receive little analgesia from codeine; ultra-rapid metabolizers produce excessive morphine, risking respiratory depression. This explains codeine's variable and unpredictable effect.