Phenoxybenzamine is FDA approved for the treatment of paroxysmal hypertension and sweating associated with the rare adrenal gland tumor, pheochromocytoma, which caused autonomic nervous system dysfunction as well as surges in catecholamines from the chromaffin cells located in the adrenal medulla. The typical use of phenoxybenzamine is prior to the resection of the pheochromocytoma. Phenoxybenzamine works to mitigate the risk of a hypertensive crisis commonly occurring during general anesthesia but can also occur during tumor handling intraoperatively.
Phenoxybenzamine was first used in 1976, in the treatment of benign prostate hyperplasia because of its known alpha-adrenergic blockade, although now, it is rarely used for this purpose.
Researchers are studying phenoxybenzamine to determine the utility as a male contraceptive. The hypothesis is that because of its known alpha-adrenergic blockade; this would result in blockage of the vas deferens muscles.
Phenoxybenzamine is a nonselective, irreversible antagonist of the alpha-adrenergic receptors. Alpha-adrenergic receptors subdivide into alpha-1 and alpha-2 receptors.
Phenoxybenzamine is an antagonist of both alpha-1 (located in smooth muscle tissue, as well as the central nervous system, gastrointestinal tract, and endocrine system) and alpha-2 receptors (found throughout the central nervous system). The mechanism by which phenoxybenzamine works is by covalently bonding with a component of the alpha-adrenergic receptor, most likely a cysteine residue, which reduces the sympathetic effects of the two hormones. This action results in an overall decrease in the vasoconstriction (catecholamine-meditated) as well as a decrease in system vascular resistance (SVR).
The mechanisms described create a vasodilative effect since the alpha-adrenergic receptors are present throughout the walls of all blood vessels), which leads to the drop in blood pressure seen. Since there is a decrease in peripheral vascular tone, the result can be a baroreceptor-mediated increase in the sympathetic tone, which is characterized by reflex tachycardia (increased heart rate). Phenoxybenzamine is often given with a beta-adrenergic antagonist to avoid the reflex tachycardia just described.
The mechanism of phenoxybenzamine involved in the urogenital system in by producing a long-lasting noncompetitive alpha blockade of the postganglionic synapses that are present in smooth muscles and endocrine glands. Phenoxybenzamine relaxes the urethra and, in turn, increases the opening of the bladder for easier emptying.
The initial phenoxybenzamine dose is once to twice daily, usually 10 mg, with an increase of 10 to 20 mg in divided doses every two to three days as needed as a means to controlling blood pressure and spells. Most commonly, the patient is usually ready for surgery within the first 7 to 14 days after initiation of phenoxybenzamine. The final dose is most typically between 20 to 100 mg daily.
The following adverse effects may occur during treatment with phenoxybenzamine:
Almost all cases will present with fatigue, nasal stuffiness, and orthostasis. Retrograde ejaculation may also occur, so men taking phenoxybenzamine should receive counsel.
According to UpToDate, these are the following contraindications and precautions when taking phenoxybenzamine:
Concerns related to adverse effects:
Concurrent drug therapy issues:
Dosage form specific issues:
• Due to case reports of cancer in humans, long-term use is not recommended.
There are no Blackbox warnings for phenoxybenzamine.
Phenoxybenzamine in Pregnancy and Nursing Mothers
Overdose of phenoxybenzamine may result in a block of the sympathetic nervous system and of the circulating adrenaline hormones (epinephrine), resulting in postural hypotension presenting with tachycardia (especially postural), dizziness or fainting, lethargy, vomiting, and shock.
According to the FDA drug label, case reports have shown the development of carcinoma associated with long-term treatment; therefore, long-term therapy is not recommended.
It is essential to appropriately manage the sympathetic nervous system symptoms of patients suffering from pheochromocytoma with first-line medication, phenoxybenzamine, an alpha-adrenergic blocker. Beta-adrenergic blockers are to be avoided before the use of alpha-adrenergic blockers due to possible profound unopposed alpha-mediated vasoconstriction that may lead to pulmonary edema and hypertensive crisis. Concurrent administration with compounds that stimulate both alpha- and beta-adrenergic receptors may result in extreme hypotensive response and tachycardia. Cardiovascular monitoring of blood pressure readings should be taken at least twice daily in both seated and standing positions.
Proper management of a drug overdose with phenoxybenzamine requires a team of healthcare professionals. Morbidity and mortality of phenoxybenzamine overdose may be high if not properly managed. Once a patient with phenoxybenzamine overdose is under the care of a healthcare team, the following should take place for the best patient outcome:
As mentioned previously, phenoxybenzamine is not recommended for long-term use due to case reports showing the development of carcinoma.
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