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Chapter: Modern Pharmacology with Clinical Applications: Antihypertensive Drugs

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Vasodilators: Sodium Nitroprusside

Sodium nitroprusside (Nipride) is a potent directly act-ing vasodilator capable of reducing blood pressure in all patients, regardless of the cause of hypertension.

Sodium Nitroprusside

Sodium nitroprusside (Nipride) is a potent directly act-ing vasodilator capable of reducing blood pressure in all patients, regardless of the cause of hypertension. It is used only by the intravenous route for the treatment of hypertensive emergencies. The pharmacological activity is caused by the nitroso moiety. The actions of the drug are similar to those of the nitrites and nitrates that are used as antianginal agents . The action of the nitrovasodilators depends on the intracellular production of cGMP.

Absorption, Metabolism, and Excretion

The onset of the hypotensive action of sodium nitro-prusside is rapid, within 30 seconds after intravenous administration. If a single dose is given, the action lasts for only a couple of minutes. Therefore, sodium nitro-prusside must be administered by continuous intra-venous infusion. After the infusion is stopped, blood pressure returns to predrug levels within 2 to 3 minutes.

 

Nitroprusside is metabolically degraded by the liver, yielding thiocyanate. Because thiocyanate is excreted by the kidney, toxicities due to this compound are most likely in patients with impaired renal function.

Pharmacological Actions

In contrast to hydralazine, minoxidil, and diazoxide, sodium nitroprusside relaxes venules as well as arteri-oles. Thus, it decreases both peripheral vascular resist-ance and venous return to the heart. This action limits the increase in cardiac output that normally follows va-sodilator therapy. Sodium nitroprusside does not inhibit sympathetic reflexes, so heart rate may increase follow-ing its administration even though cardiac output is not

increased. Renal blood flow remains largely unaffected by sodium nitroprusside, because the decrease in renal vascular resistance is proportional to the decrease in mean arterial pressure. As with all vasodilators, plasma renin activity increases.

Clinical Uses

Sodium nitroprusside is used in the management of hy-pertensive crisis. Although it is effective in every form of hypertension because of its relatively favorable effect on cardiac performance, sodium nitroprusside has spe-cial importance in the treatment of severe hypertension with acute myocardial infarction or left ventricular fail-ure. Because the drug reduces preload (by venodila-tion) and afterload (by arteriolar dilation), it improves ventricular performance and in fact is sometimes used in patients with refractory heart failure, even in the ab-sence of hypertension.

Adverse Effects

The most commonly encountered side effects of sodium nitroprusside administration are nausea, vomiting, and headache, which quickly dissipate when the infusion is terminated. When sodium nitroprusside treatment ex-tends for several days, there is some danger of toxicity owing to the accumulation of its thiocyanate metabo-lite. Thiocyanate intoxication includes signs of delirium and psychosis; hypothyroidism also may occur. If nitro-prusside is administered for several days, thiocyanate levels should be monitored.

Close supervision is required when nitroprusside is used because of the drug’s potency and short duration of action.

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