Hypertensive crises secondary to monoamine oxidase inhibitor-tyramine interactions. Severe paroxysmal hypertension complicated by intracerebral or subarachnoid hemorrhage, hypertensive encephalopathy, or acute hypertensive heart failure can occur in patients treated with monoamine oxidase (MOA) inhibitors after ingestion of certain drugs or tyramine-containing foods [48,49]. Because MAO is required for degradation of intracellular amines, including epinephrine, norepinephrine, and dopamine, MAO inhibitors lead to accumulation of catecholamines within storage granules in nerve terminals. The amino acid tyramine is a potent inducer of neurotransmitter release from nerve terminals. As a result of inhibition of hepatic MAO, ingested tyramine escapes oxidative degradation in the liver. In addition, the high circulating levels of tyramine provoke massive catecholamine release from nerve terminals, resulting in vasoconstriction and a paroxysm of severe hypertension. A hyper-adrenergic syndrome resembling pheochromocytoma then ensues. Symptoms include severe pounding headache, flushing or pallor, profuse diaphoresis, nausea, vomiting, and extreme prostration. The mean increase in blood pressure is 55 mm Hg systolic and 30 mm Hg diastolic . The duration of the attacks varies from 10 minutes to 6 hours. Attacks can be provoked by the ingestion of foods known to be rich in tyramine: natural or aged cheeses, Chianti wines, certain imported beers, pickled herring, chicken liver, yeast, soy sauce, fermented sausage, coffee, avocado, banana, chocolate, and canned figs. Sympathomimetic amines in nonprescription cold remedies also can provoke neurotransmitter release in patients treated with an MAO inhibitor. Either sodium nitroprusside or phentolamine can be used to manage this type of hypertensive crisis. Because most patients are normotensive before onset of the crisis the goal of blood pressure treatment should be normalization of the blood pressure. After blood pressure control, intravenous ^-blockers may also be required to control heart rate and tachyarrhythmias. Because the MAO inhibitor-tyramine hypertensive crisis is self-limited, parenteral antihypertensive agents can be weaned without institution of oral antihypertensive agents.
Mechanism of action and metabolism of nitroprusside
Mechanism of action and metabolism of nitroprusside. Sodium nitroprusside is the drug of choice for management of virtually all hypertensive crises, including malignant hypertension, hypertensive encephalopathy, acute hypertensive heart failure, intracerebral hemorrhage, perioperative hypertension, catecholamine-related hypertensive crises, and acute aortic dissection (in combination with a ^-blocker) [1,50]. Sodium nitroprusside is a potent intravenous hypotensive agent with immediate onset and brief duration of action. The site of action is the vascular smooth muscle. Nitroprusside has no direct action on the myocardium, although it may affect cardiac performance indirectly through alterations in systemic hemodynamics. Nitroprusside is an iron (Fe) coordination complex with five cyanide moieties and a nitroso (NO) group. The nitroso group combines with cysteine to form nitrosocysteine and other short-acting S-nitrosothiols. Nitrosocysteine is a potent activator of guanylate cyclase, thereby causing cyclic guanosine monophosphate (cGMP) accumulation and relaxation of vascular smooth muscle [51,52]. Nitroprusside causes vasodilation of both arteriolar resistance vessels and venous capacitance vessels. Its hypotensive action is a result of a decrease in systemic vascular resistance. The combined decrease in preload and afterload reduces myocardial wall tension and myocardial oxygen demand. The net effect of nitroprusside on cardiac output and heart rate depends on the intrinsic state of the myocardium. In patients with left ventricular (LV) systolic dysfunction and elevated LV end-diastolic pressure, nitroprusside causes an increase in stroke volume and cardiac output as a result of afterload reduction and heart rate may actually decrease in response to improved cardiac performance. In contrast, in the absence of LV dysfunction, venodi-lation and preload reduction can result in a reflex increase in sympathetic tone and heart rate. For this reason, nitroprusside must be used in conjunction with a ^-blocker in acute aortic dissection. The hypotensive action of nitroprusside appears within seconds and is immediately reversible when the infusion is stopped. The cGMP in vascular smooth muscle is rapidly degraded by cGMP-specific phos-phodiesterases. Nitroprusside is rapidly metabolized with a half-life (tl/2) of 3 to 4 minutes. Cyanide is formed as a short-lived intermediate product by direct combination with sulfhydryl (SH) groups in ery-throcytes and tissues. The cyanide groups are rapidly converted to thiocyanate by the liver in a reaction in which thiosulfate acts as a sulfur donor. Thiocyanate is excreted by the kidneys, with a half-life of 1 week in patients with normal renal function. Thiocyanate accumulation and toxicity can occur when a high-dose or prolonged infusion is required, especially in patients with renal insufficiency. When these risk factors are present, thiocyanate levels should be monitored and the infusion stopped if the level is over 10 mg/dL. Thiocyanate toxicity is rare in patients with normal renal function requiring less than 3 ^g/kg/min for less than 72 hours . Cyanide poisoning is a very rare complication, unless hepatic clearance of cyanide is impaired by severe liver disease or massive doses of nitroprusside (over 10 ^g/kg/min) are used to induce deliberate hypotension during surgery .
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...