NAVLE Veterinary Pharmacology 4

Question 1

A 6-year-old Doberman Pinscher is being treated for dilated cardiomyopathy with digoxin. The dog develops acute renal failure secondary to a urinary obstruction. Which pharmacokinetic change requires the MOST urgent dose adjustment?

Accepted Answer

Reduced renal clearance causing digoxin accumulation and toxicity

Answer

Digoxin is primarily eliminated by renal excretion (60-75% unchanged in urine). Acute renal failure dramatically reduces digoxin clearance, causing drug accumulation and a narrow therapeutic index means toxicity (arrhythmias, GI signs, neurological effects) develops rapidly. Dose reduction or extended dosing intervals are mandatory. Digoxin has minimal hepatic first-pass effect, and renal failure typically decreases (not increases) protein binding and volume of distribution.

Question 2

A llama is treated with flunixin meglumine IV at the bovine label dose for 5 consecutive days for GI pain. Which adverse effect is MOST likely due to the species-specific pharmacokinetic difference compared to cattle?

Accepted Answer

Nephrotoxicity worsened by the llama's slower drug elimination half-life

Answer

Camelids (llamas, alpacas) have a significantly longer elimination half-life for flunixin meglumine (~10-12 hours) compared to cattle (~3-4 hours). Using the bovine dose and frequency leads to drug accumulation in camelids, with renal papillary necrosis and nephrotoxicity being the primary concern due to sustained COX-1 inhibition reducing renal prostaglandin synthesis. Right dorsal colitis is classically associated with horses on prolonged NSAIDs, not camelids.

Question 3

A 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 mechanism best explains this idiosyncratic reaction, and what is the appropriate next step?

Accepted Answer

Type IV delayed hypersensitivity reaction; discontinue methimazole and consider radioiodine or surgical thyroidectomy

Answer

Facial pruritus and excoriation is a well-documented idiosyncratic adverse effect of methimazole in cats, occurring in approximately 2-3% of treated cats. It represents a Type IV (cell-mediated) delayed hypersensitivity reaction typically appearing within the first month of therapy. This reaction necessitates discontinuation of methimazole; dose reduction is not appropriate as re-exposure will trigger recurrence. Alternative management includes carbimazole (prodrug of methimazole, so cross-reactivity is possible), radioactive iodine (I-131), or surgical thyroidectomy.

Question 4

You are treating a 450 kg horse with a severe gram-negative septicemia. You choose gentamicin and wish to use pharmacokinetic/pharmacodynamic (PK/PD) optimization. Which dosing strategy best exploits gentamicin's concentration-dependent killing and post-antibiotic effect (PAE)?

Accepted Answer

6.6 mg/kg IV every 24 hours (once-daily dosing) to maximize Cmax:MIC ratio while allowing renal recovery

Answer

Aminoglycosides like gentamicin exhibit concentration-dependent killing — efficacy correlates with peak (Cmax) to MIC ratio (target Cmax:MIC ≥8-10:1) rather than time above MIC. They also have a prolonged post-antibiotic effect (PAE), meaning bacterial suppression continues even after serum concentrations fall below MIC. Once-daily dosing (6.6 mg/kg q24h in horses) maximizes the Cmax:MIC ratio, exploits the PAE, and critically allows trough concentrations to fall near zero, reducing tubular aminoglycoside accumulation and nephrotoxicity risk. Continuous infusion or time-dependent dosing strategies are appropriate for beta-lactams, not aminoglycosides.

Question 5

A 3-year-old intact male ferret presents with insulinoma-related hypoglycemia. The clinician elects to use diazoxide as medical management. Which mechanism of action makes diazoxide appropriate for this condition?

Accepted Answer

It opens ATP-sensitive potassium channels in pancreatic beta cells, hyperpolarizing the membrane and inhibiting insulin release

Answer

Diazoxide acts by opening ATP-sensitive potassium channels (K-ATP channels) in pancreatic beta cells. This hyperpolarizes the cell membrane, preventing calcium influx through voltage-gated calcium channels, and thereby inhibiting insulin exocytosis. This directly counteracts the excessive autonomous insulin secretion from insulinoma cells. In contrast, sulfonylureas (like glipizide) close these same K-ATP channels, stimulating insulin release — making them contraindicated in insulinoma. Glucokinase inhibition, GLUT-2 blockade, or glucagon receptor agonism are not diazoxide's mechanisms.

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE - North American Veterinary Licensing Examination Practice Test

NAVLE Veterinary Pharmacology 4