Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

CAPTOPRIL

Chemistry - Related to a peptide isolated from the venom of a South American pit viper, captopriloccurs as a slightly sulfurous smelling, white to off-white, crystalline powder. It is freely soluble inwater and in alcohol.

Storage, Stability, Compatibility

Captopril tablets should be stored at a temperature not greaterthan 30°C, and in tight containers.

Pharmacology - CAPTOPRIL

Captopril prevents the formation of angiotensin II (a potent vasoconstrictor) bycompeting with angiotensin I for the enzyme angiotensin converting enzyme (ACE). ACE has amuch higher affinity for captopril than for angiotensin I. Because angiotensin II concentrations aredecreased, aldosterone secretion is reduced and plasma renin activity is increased.
The cardiovascular effects of captopril in patients with CHF include decreased total peripheralresistance, pulmonary vascular resistance, mean arterial and right atrial pressures, and pulmonarycapillary wedge pressure; no change or decrease in heart rate; and increased cardiac index andoutput, stroke volume, and exercise tolerance. Renal blood flow can be increased with little changesin hepatic blood flow.

Uses, Indications

The principle uses of captopril in veterinary medicine at present, are as a vasodilator in the treatment of CHF and in the treatment of hypertension. It is being explored as adjunctive treatment in chronic renal failure and in protein losing nephropathies.

Pharmacokinetics - CAPTOPRIL

In dogs, approximately 75% of an oral dose is absorbed, but food in the GItract reduces bioavailability by 30-40%. It is distributed to most tissues (not the CNS) and is 40%bound to plasma proteins in dogs. Captopril crosses the placenta and only about 1% of plasmaconcentrations are found in milk. The half-life of captopril is about 2.8 hours in dogs and less than2 hours in humans. The drug is metabolized and renally excreted. More than 95% of a dose isexcreted renally, both as unchanged (45-50%) drug and as metabolites. Patients with significantrenal dysfunction can have significantly prolonged half-lives.
Contraindications/Precautions - Captopril is contraindicated in patients who have demonstratedhypersensitivity to the ACE inhibitors. It should be used with caution and close supervision, inpatients with renal insufficiency and doses may need to be reduced.
Captopril should also be used with caution in patients with hyponatremia or sodium depletion, coronary or cerebrovascular insufficiency, preexisting hematologic abnormalities or a collagenvascular disease (e.g SLE).
Patients with severe CHF should be monitored very closely upon initiation of therapy.

Adverse Effects, Warnings

There have been some reports of hypotension, renal failure, hyperkalemia, vomiting and diarrhea developing in dogs after captopril administration. Although seen inpeople, skin rashes (4-7% incidence) and neutropenia/agranulocytosis (rare) have not been reportedin dogs.
Overdosage - In overdose situations, the primary concern is hypotension; supportive treatment withvolume expansion with normal saline is recommended to correct blood pressure. Dogs given 1.5gm/kg orally developed emesis and decreased blood pressure.

Drug Interactions

Concomitant diuretics, or other vasodilators may cause hypotension if used with captopril; titrate dosages carefully. Hyperkalemia may develop if given with potassium or potassium sparing diuretics (e.g spironolactone).
Digoxin levels may increase 15-30% when captopril is added, automatic reduction in dosage is not recommended, but monitoring of serum digoxin levels should be performed.
Non-steroidal anti-inflammatory agents (NSAIDs) may reduce the clinical efficacy of captopril when it is being used as an antihypertensive agent.
Reduced oral absorption of captopril may occur if given concomitantly with antacids. It is suggested to separate dosing by at least two hours. Probenecid can decrease renal excretion of captopril and possibly enhance the clinical and toxic effects of the drug.
Cimetidine and captopril used concomitantly has caused neurologic dysfunction in two human patients.
Laboratory Interactions - Captopril may cause a false positive urine acetone test (sodium nitroprusside reagent). When using iodohippurate sodium I123/I134 or Technetium Tc99 pententate renal imaging in patients with renal artery stenosis, ACE inhibitors may cause a reversible decrease in localization and excretion of these agents in the affected kidney which may lead confusion in test interpretation.
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