Secondary hypertension
There are many causes of secondary hypertension, but curable secondary hypertension is rarely encountered (probably less than 2% of all hypertensive patients). Secondary hypertension should be especially considered in those patients with severe hypertension, hypertension refractory to medical therapy, the young (less than 35 years), and patients with progressive target damage or advanced retinopathy with hemorrhages, exudates, or papilledema. However, to what extent these factors are actually associated with increased risk of secondary hypertension is unknown. A rapid increase of severity of diastolic blood pressure in a patient with extensive atherosclerotic disease or advanced age suggests the possibility of renovascular hypertension.
Pheochromocytoma
Pheochromocytoma, an endocrine tumor of the adrenal medulla or sympathetic chain, secretes potentially enormous quantities of catecholamines such as norepinephrine and epinephrine in an unregulated fashion. This tumor is life-threatening, has many possible presentations, and can be difficult to diagnose. Approaches to treatment of this rare disease vary from center to center and available information of necessity is generally observational rather than stemming from controlled clinical trials. Depending on circumstances, patients with diagnosed pheochromocytoma often are treated with α-adrenergic blocking agents, generally using the irreversible antagonist phenoxybenzamine, followed by β-adrenergic blocking agents if necessary. Phenoxybenzamine is usually dosed empirically, starting at 10 mg/day, with dose increments determined by symptoms and control of blood pressure. Evidence of the adequacy of α-adrenergic receptor blockade can include worsening postural hypotension and nasal stuffiness. Some patients may require 60 mg/day or more to control their hypertensive episodes. Phenoxybenzamine has also been used as long-term therapy in surgically incurable patients. The reversible and rapidly acting α-adrenergic receptor antagonist phentolamine has been used for controlling hypertensive crises that complicate pheochromocytoma. Although this is theoretically an attractive drug in this setting, very few physicians are experienced in its use. Indeed, case-report data suggests that rapid infusions of phentolamine may cause sudden and severe hypotension in patients with pheochromocytoma. Because of this, it may be preferable for physicians to use more familiar drugs, such as sodium nitroprusside, in the treatment of hypertensive emergencies in patients with pheochromocytoma.
Principles
The best drug to use in an emergency might be a familiar one rather than a theoretically preferable agent that is almost never used in medical practice.
Methyl paratyrosine, a competitive inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine synthesis, may be useful in treating patients with incurable pheochromocytoma.
Renovascular hypertension
Renovascular hypertension is defined as hypertension caused by a narrowing of the renal artery (or arteries). This disease occurs more commonly in patients with risk factors for atherosclerosis or evidence of atherosclerosis in the abdominal vessels or elsewhere (e.g., the smoker with peripheral vascular disease). There are still not enough data to determine whether medical or surgical (bypass or angioplasty) therapy is superior, but surgical therapy appears to be useful in the setting of renal insufficiency, a small kidney, or bilateral disease, and of course when medical therapy fails. Investigation should not be undertaken unless the decision has been made a priori to repair the renal artery if a lesion is found.
Principles
Do not order tests that will not affect diagnosis or management.
Multiple drug regimens are usually necessary owing to the severity of the hypertension. Even after successful revascularization, drug therapy is often necessary, especially in older patients with atherosclerosis.
Primary aldosteronism
Primary hyperaldosteronism is a disease produced by oversecretion of aldosterone, either from a unilateral lesion or from disease in both adrenal glands. It is commonly associated with hypokalemia. Spironolactone, a specific competitive antagonist of aldosterone, is a medical therapy commonly used to treat primary hyperaldosteronism, especially in patients with bilateral disease or in those who are not candidates for surgery. Although spironolactone is theoretically a very attractive drug for treating this disease, male patients may be especially bothered by the gynecomastia and sexual dysfunction that often accompany treatment with spironolactone. Amiloride may be efficacious in ameliorating hypokalemia and hypertension due to hyperaldosteronism. Whether long-term blockage of aldosterone receptors expressed throughout the body has any benefit in these patients is not known.
Drug-induced hypertension is a potentially reversible cause of secondary hypertension. For example, immunosuppressive drugs such as cyclosporine and high-dose glucocorticoids may commonly cause or worsen hypertension. Recombinant erythropoietin frequently increases blood pressure in patients receiving therapy for anemia associated with severe renal failure. Use of oral contraceptives has been associated with an increased risk of hypertension. Drugs such as cocaine and amphetamines should be considered in the emergency setting of severe unexplained hypertension.
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