NAVLE Veterinary Pharmacology 5

Question 1

A 7-year-old intact male dog is being treated with ketoconazole for a systemic fungal infection. The owner also mentions the dog is on cyclosporine for immune-mediated thrombocytopenia. Which pharmacokinetic mechanism best explains the expected drug interaction between these two agents?

Accepted Answer

Ketoconazole inhibits CYP3A4, reducing cyclosporine metabolism and increasing its plasma concentration

Answer

Ketoconazole is a potent inhibitor of cytochrome P450 3A4 (CYP3A4), the primary enzyme responsible for cyclosporine metabolism. Inhibition of this enzyme markedly reduces cyclosporine clearance, leading to elevated plasma concentrations and potential nephrotoxicity and neurotoxicity. Clinicians sometimes exploit this interaction intentionally to reduce cyclosporine dosing costs, but it requires careful monitoring.

Question 2

A cat presents with acute rodenticide toxicosis from ingestion of brodifacoum. Vitamin K1 therapy is initiated. Which statement best describes the pharmacodynamic basis for why high doses and prolonged treatment (3–6 weeks) are required compared to warfarin toxicosis?

Accepted Answer

Brodifacoum undergoes extensive enterohepatic recirculation, maintaining toxic tissue concentrations long after ingestion

Answer

Brodifacoum is a long-acting anticoagulant rodenticide with extensive enterohepatic recirculation and high lipophilicity, resulting in a plasma half-life of weeks to months in companion animals. This prolonged tissue retention means that even after a single ingestion, the drug continues to inhibit vitamin K epoxide reductase for an extended period. Treatment with vitamin K1 must continue until all brodifacoum is eliminated, typically 3–6 weeks, verified by PT/aPTT testing 48–72 hours after cessation.

Question 3

A horse is prescribed rifampin as part of a combination regimen for Rhodococcus equi pneumonia. The foal is also receiving erythromycin. Three weeks into therapy, serum erythromycin levels are subtherapeutic despite appropriate dosing. What is the most likely mechanism?

Accepted Answer

Rifampin induces hepatic CYP3A4 and P-glycoprotein, markedly increasing erythromycin metabolism and efflux

Answer

Rifampin is a potent inducer of cytochrome P450 enzymes (particularly CYP3A4) and P-glycoprotein. Erythromycin is a CYP3A4 substrate and P-glycoprotein substrate. Rifampin induction increases both first-pass hepatic metabolism and intestinal P-gp-mediated efflux of erythromycin, dramatically reducing its systemic bioavailability and plasma concentrations. This interaction is clinically significant in R. equi treatment and may compromise efficacy; azithromycin is often preferred as an alternative macrolide in this context.

Question 4

A veterinarian prescribes phenobarbital to a 4-year-old epileptic dog. After 6 months of stable seizure control, breakthrough seizures occur despite unchanged dosing. Serum phenobarbital levels are now below therapeutic range. No drug interactions or compliance issues are identified. What pharmacokinetic phenomenon best explains this finding?

Accepted Answer

Phenobarbital induces its own hepatic metabolism (autoinduction) via CYP enzyme upregulation

Answer

Phenobarbital is a classic example of autoinduction — it induces the hepatic cytochrome P450 enzymes (particularly CYP2B and CYP3A) responsible for its own metabolism. With chronic administration, enzyme induction progressively accelerates phenobarbital clearance, causing serum levels to fall below therapeutic range even at a fixed dose. This typically occurs within weeks to months and necessitates dose escalation. Therapeutic drug monitoring is essential; target serum levels in dogs are 20–40 µg/mL.

Question 5

A 10 kg dog receives a constant rate infusion of lidocaine at 50 µg/kg/min for ventricular arrhythmia management post-cardiac surgery. After 8 hours, the dog develops muscle tremors and seizures. Serum lidocaine concentration is 8 µg/mL (toxic range >6 µg/mL in dogs). Which factor most likely contributed to lidocaine accumulation in this patient?

Accepted Answer

Reduced hepatic blood flow or hepatic dysfunction impairs lidocaine clearance, since it is a high-extraction drug

Answer

Lidocaine is a high hepatic extraction ratio drug (extraction ratio ~0.7 in dogs), meaning its clearance is primarily limited by hepatic blood flow rather than enzyme capacity. In post-surgical patients, reduced cardiac output, hepatic hypoperfusion, or overt hepatic dysfunction can dramatically reduce lidocaine clearance, leading to accumulation during CRI. This is distinct from low-extraction drugs where enzyme activity is the rate-limiting step. CNS toxicity (tremors, seizures) is the primary manifestation of lidocaine overdose in dogs.

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE Veterinary Pharmacology 5