NAVLE Veterinary Pharmacology 6

Question 1

A 4-year-old Greyhound is prescribed phenobarbital for epilepsy. Compared to a Labrador Retriever of the same weight, which pharmacokinetic difference most significantly affects dosing in Greyhounds?

Accepted Answer

Greyhounds have a lower volume of distribution for lipophilic drugs due to minimal body fat, resulting in higher plasma concentrations

Answer

Greyhounds have exceptionally low body fat (1–3% vs. 15–25% in mixed breeds). Phenobarbital is a lipophilic drug that distributes into adipose tissue. With minimal fat stores, the volume of distribution is reduced, leading to higher peak plasma concentrations at standard mg/kg doses. This means Greyhounds are at greater risk for toxicity and often require lower initial doses. Hepatic clearance differences exist for some drugs (e.g., propofol, thiopental) but are not the primary concern with phenobarbital dosing.

Question 2

A cow in early lactation is treated with systemic flunixin meglumine (2.2 mg/kg IV) for acute coliform mastitis. Which mechanism best explains why this NSAID may paradoxically worsen endotoxemia outcomes despite reducing fever?

Accepted Answer

Blockade of prostacyclin (PGI2) synthesis removes a protective vasodilatory signal in splanchnic vasculature, worsening gut ischemia

Answer

In endotoxemia, prostacyclin (PGI2) serves a protective role in maintaining splanchnic blood flow through vasodilation. Flunixin inhibits both COX-1 and COX-2, blocking PGI2 synthesis. Loss of this protective vasodilation in the gut vasculature worsens mucosal ischemia and intestinal barrier failure, potentially allowing greater endotoxin translocation. While fever reduction is clinically desirable, the trade-off in severe endotoxemia is impaired splanchnic perfusion. This explains why outcome data on NSAID use in severe bovine endotoxemia is mixed and dose timing matters.

Question 3

A veterinarian administers a drug that causes dose-dependent sinus bradycardia in a horse. Atropine is given but produces no improvement. Which drug class most likely caused this atropine-resistant bradycardia?

Accepted Answer

Calcium channel blocker (e.g., diltiazem)

Answer

Calcium channel blockers such as diltiazem decrease SA node automaticity and AV node conduction by blocking L-type calcium channels — a mechanism entirely independent of muscarinic receptors. Atropine works by blocking vagal (parasympathetic) tone via muscarinic receptor antagonism. Because diltiazem's bradycardic effect does not rely on acetylcholine-mediated vagal input, atropine cannot reverse it. Alpha-2 agonists (e.g., detomidine) cause bradycardia primarily through increased vagal tone and are at least partially responsive to atropine. Opioids cause mild bradycardia that is vagally mediated and atropine-responsive. Digoxin toxicity may respond partially to atropine for its vagomimetic effects.

Question 4

A dog with a confirmed MDR1 (ABCB1) mutation (homozygous mutant) requires antiparasitic treatment for generalized demodicosis. Which drug combination poses the GREATEST risk of neurotoxicity in this patient?

Accepted Answer

Ivermectin + ketoconazole

Answer

Ivermectin is a P-glycoprotein (P-gp) substrate; in MDR1-mutant dogs, reduced P-gp function allows accumulation of ivermectin in the CNS. Ketoconazole is a potent CYP3A4 and P-glycoprotein inhibitor. Co-administration of ketoconazole with ivermectin in a P-gp-deficient dog compounds the risk dramatically: ivermectin is already not being effluxed from the CNS, and ketoconazole further inhibits any residual P-gp activity and slows ivermectin hepatic metabolism. This combination has caused fatal neurotoxicity. Milbemycin + spinosad is approved for use in MDR1-mutant dogs at label doses. Selamectin has a wide safety margin even in MDR1-mutant dogs. Doramectin carries risk in MDR1 dogs, but the combination with doxycycline does not add a pharmacokinetic interaction that amplifies CNS accumulation.

Question 5

A 6-year-old DSH cat with hyperthyroidism is started on methimazole. Two weeks later, the owner reports the cat is scratching its face intensely and has developed facial excoriations. Which statement BEST explains the pathophysiology and recommended management?

Accepted Answer

Facial pruritus is a known idiosyncratic drug reaction in cats, likely immune-mediated; discontinue methimazole and consider carbimazole or alternative definitive therapy

Answer

Facial pruritus and self-excoriation is a well-documented idiosyncratic adverse effect of methimazole in cats, occurring in approximately 2–3% of treated cats, typically within the first 1–3 months of therapy. The mechanism is thought to be immune-mediated. This reaction is an indication to discontinue methimazole immediately, as continued use can lead to more severe reactions including hepatotoxicity, thrombocytopenia, or agranulocytosis. Carbimazole (a prodrug of methimazole) should theoretically cross-react, so definitive therapy with I-131, surgical thyroidectomy, or a prescription iodine-restricted diet (Hill's y/d) is preferred. This is not a dose-dependent effect and dose reduction is inadequate management.

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE Veterinary Pharmacology 6