Antimicrobial and Chemotherapeutic Agents Flashcards

A patient is prescribed penicillin for a gram-positive bacterial infection. What is the primary mechanism by which this antibiotic exerts its bactericidal effect?

Answer: Inhibition of transpeptidase, preventing peptidoglycan cell wall cross-linking.

Penicillins are beta-lactam antibiotics that work by irreversibly inhibiting the transpeptidase enzyme (also known as a penicillin-binding protein). This enzyme is crucial for the final step in peptidoglycan synthesis, which involves cross-linking the peptide chains to form a rigid cell wall. By blocking this process, penicillins weaken the cell wall, leading to cell lysis and bacterial death.

A 68-year-old male with a history of atrial fibrillation, well-controlled on warfarin, is diagnosed with oropharyngeal candidiasis and is prescribed a course of oral fluconazole. What is the most significant potential interaction the pharmacist should be concerned about?

Answer: Inhibition of warfarin metabolism, leading to a supratherapeutic INR and increased risk of bleeding.

Fluconazole is a potent inhibitor of the cytochrome P450 enzyme CYP2C9, which is the primary enzyme responsible for metabolizing the more active S-isomer of warfarin. By inhibiting this enzyme, fluconazole decreases the clearance of warfarin, leading to higher plasma concentrations, an elevated International Normalized Ratio (INR), and a significantly increased risk of serious bleeding.

Which of the following statements most accurately describes the mechanism of action of acyclovir in treating a herpes simplex virus (HSV) infection?

Answer: It is a guanosine analog that, after phosphorylation by viral thymidine kinase, inhibits viral DNA polymerase and causes chain termination.

Acyclovir is a prodrug that is selectively activated in cells infected with herpes viruses. The viral enzyme thymidine kinase monophosphorylates acyclovir. Host cell kinases then convert it to acyclovir triphosphate, which competitively inhibits the viral DNA polymerase and is also incorporated into the growing viral DNA chain, causing chain termination. This specificity for the viral enzyme accounts for its selective toxicity.

A patient undergoing chemotherapy with a regimen that includes cisplatin is closely monitored for adverse effects. Which of the following is a well-known and often dose-limiting toxicity of this agent?

Answer: Nephrotoxicity

Cisplatin is a heavy metal compound notorious for causing significant, cumulative, and dose-limiting nephrotoxicity. It accumulates in the renal tubules, leading to direct cellular damage, acute kidney injury, and electrolyte wasting. Management includes aggressive pre- and post-treatment hydration to mitigate this effect. Cardiotoxicity is associated with doxorubicin, pulmonary fibrosis with bleomycin, and hemorrhagic cystitis with cyclophosphamide.

A patient is admitted with a severe skin and soft tissue infection. Cultures grow Staphylococcus aureus that is resistant to oxacillin. This resistance is conferred by the mecA gene. What is the primary mechanism of resistance in this organism?

Answer: Alteration of the drug's target site, the penicillin-binding protein (PBP).

Methicillin-resistant Staphylococcus aureus (MRSA) resistance is primarily due to the acquisition of the mecA gene. This gene encodes for a novel penicillin-binding protein, PBP2a. PBP2a has a very low affinity for all beta-lactam antibiotics, allowing the bacteria to continue synthesizing its cell wall even in the presence of these drugs, rendering them ineffective.

Metronidazole is a unique antimicrobial agent prescribed for a variety of infections. Its spectrum of activity is primarily limited to which of the following classes of organisms?

Answer: Anaerobic bacteria and certain protozoa

Metronidazole is a prodrug that requires reductive activation of its nitro group, a process that can only occur in the low-redox-potential environment found within anaerobic organisms. Therefore, its spectrum is limited to obligate anaerobic bacteria (e.g., Bacteroides, Clostridium) and certain protozoa (e.g., Trichomonas, Giardia, Entamoeba). It has no clinically significant activity against aerobic bacteria.