Sodium nitroprusside is a potent arteriolar and venodilator drug with a similar mechanism of action to the organic nitrates, h has a very short duration of action and is administered by continuous intravenous infusion starting at an initial infusion rate of 1-5 μg kg-1 min-1. It reduces pulmonary and systemic vascular resistance decreasing ventricular filling pressure and is most useful in the management of acute, life-threatening cardiogenic pulmonary oedema. The dose can be titrated upwards to effect whilst monitoring arterial blood pressure since excessive falls in arterial blood pressure are an indication of overdosage. The effects are reversed within 1-10 min of slowing the infusion rate allowing fine control of the drug’s effects. Since delivery of the drug requires accurate control at a low rate of fluid administration, an infusion pump should be used. In dogs with severe cardiac failure resulting from poor systolic function (dilated cardiomyopathy), a drug providing positive inotropic support (for example dobutamine) is required in addition to sodium nitroprusside, otherwise the reduction in preload caused by venodilation may result in a precipitous fall in cardiac output. Intravenous infusion of sodium nitroprusside should not exceed 48 h since toxic metabolites (thiocyanate) build up in the circulation. Infusions should be stopped gradually rather than abruptly to prevent rebound increases in vascular resistance and cardiac filling pressures.
Prazosin is a balanced vasodilator drug which can be given orally to dogs. It is an alpha1-selective adrenoceptor antagonist which blocks excessive sympathetic stimulation of vascular alpha1-adrenoceptors without affecting the autoinhibition of noradrenaline release by presynaptic alpha2-adrenoceptors. The recommended dosage is 1 mg tid for dogs weighing less than 15 kg and 2 mg tid for dogs weighing more than 15 kg. In humans and experimental animals, although prazosin is very effective initially, with repeated dosing its effects become attenuated, possibly as the renin-angiotensin system assumes greater importance in regulating vascular tone.
Angiotensin converting enzyme inhibitors
Given the effects of angiotensin II which are central to the pathophvsiology of chronic heart failure, the effects of drugs which inhibit the formation of angiotensin II by inhibition of anglotensin converting enzyme (ACE) are predictable. They are balanced vasodilators and will enhance the excretion of sodium and water by reducing circulating levels of aldosterone and ADH; thus they have a potassium-sparing diuretic effect. Angiotensin converting enzyme is also responsible for the breakdown of the natural vasodilator, bradykinin and some of the effects of ACE inhibitors can be attributed to potentiating bradykinin. Their effects on the vasculature are less profound and slower to take effect when compared to hydralazine and nitroprusside, hence these drugs are preferred to the ACE inhibitors when dealing with cases of life-threatening pulmonary oedema due to left-sided heart failure. Indeed, clinical signs may continue to improve for several weeks in human heart failure patients on ACE inhibitors and multicentre controlled clinical trials in veterinary medicine suggest that the same is true in veterinary medicine. Small but significant effects have been demonstrated on survival time of dogs with dilated cardiomyopathy and mitral valvular heart disease treated with enalapril.
Captopril was the first ACE inhibitor to be produced. It contains a sulphydryl group which causes certain side effects which are common to sulphydryl compounds, namely alterations in taste perception, proteinuria and drug-induced blood dyscrasias. The recommended dosage is 0.5-2.0 mg kgr-1 three times daily. Oral absorption is reduced by food. Exceeding the upper limit of this dose gives no further beneficial therapeutic effect but increases the drug’s toxiciry. Angiotensin II may maintain glomerular filtration pressures in the face of poor renal perfusion by constricting the efferent arteriole more than the afferent arteriole. Removal of this protective mechanism may precipitate acute renal failure in some patients with subclinical, pre-existing renal dysfunction. Hence blood plasma urea and creatinine should be determined in animals before and after they are put on ACE inhibitors. As with other vasodilator drugs, hypotension is a possible side effect, particularly if used in combination with high doses of diuretics. In humans. ACE inhibition has been associated with a drug-induced cough.
Enalapril is an ACE inhibitor with significant advantages over captopril. It does not possess a sulphydryl group and so lacks the associated side effects mentioned above. It is a pro-drug, the active form being a metabolite, enalaprilat, formed by the liver. The onset of action is slower than captopril and its duration of effect is longer (12-14 h). Recommended dosing in dogs is 0,5-1.0 mg kg-1 every 12-24 h and in cats is 0,25 mg kg-1 every 12 h. Side effects are those associated with ACE inhibition described above for captopril.
Benazepril is an ACE inhibitor recently licensed for veterinary use. It shares many properties with enalapril, lacking a sulphydryl group and being a pro-drug. In addition, the excretion of the active metabolite from the body occurs both in the bile and the urine. This contrasts with enalapril, which is eliminated in the urine only where dose adjustment may be necessary in animals with significant impairment of renal function. The recommended dose rate of benazepril for the dog is 0.25 to 0.5 mg kg-1 orally every 24 hours. Currently, there is no authorized dose rate for cats.