Medication Summary
Medical therapy is used for preoperative preparation prior to surgical resection, [70] for acute hypertensive crises, and as primary therapy for patients with metastatic pheochromocytomas. Preoperative preparation requires combined alpha and beta blockade to control blood pressure and to prevent an intraoperative hypertensive crisis. Alpha-adrenergic blockade, in particular, is required to control blood pressure and prevent a hypertensive crisis. High circulating catecholamine levels stimulate alpha receptors on blood vessels and cause vasoconstriction.
Beta blockers are used if significant tachycardia occurs after alpha blockade. Beta blockers are not administered until adequate alpha blockade has been established, however, because unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis. Noncardioselective beta blockers, such as propranolol (Inderal) or nadolol (Corgard), are the usual choice; however, cardioselective agents, such as atenolol (Tenormin) and metoprolol (Lopressor), also may be used.
Labetalol (Trandate, Normodyne) is a noncardioselective beta-adrenergic blocker and selective alpha-adrenergic blocker that has been shown to be effective in controlling hypertension associated with pheochromocytoma. However, it has also been associated with paradoxic episodes of hypertension thought to be secondary to incomplete alpha blockade. Thus, its use in the preoperative treatment of patients with pheochromocytoma is controversial.
During surgery, intravenous phentolamine, a rapid-acting alpha-adrenergic antagonist, is used to control blood pressure. Rapid-acting intravenous beta blockers, such as esmolol, are also used to normalize blood pressure.
Selective alpha1 blocking agents, such as prazosin (Minipress), terazosin (Hytrin), and doxazosin (Cardura), have more favorable adverse effect profiles and are used when long-term therapy is required (metastatic pheochromocytoma). These medications are not used to prepare patients for surgery, because of their incomplete alpha blockade.
Iobenguane I 131 was approved by the US Food and Drug Administration (FDA) in July 2018 for iobenguane scan–positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma in patients aged 12 years or older in whom systemic anticancer therapy is needed. The drug’s efficacy was demonstrated in a single-arm, open-label, phase-2 clinical trial performed under a special protocol assessment with the FDA. Seventeen (25%) of the study’s 68 evaluable patients were able to reduce all antihypertensive medication by 50% or more for at least 6 months; 15 patients (22%) obtained an overall tumor response. [71]
Alpha Blockers, Antihypertensives
Phenoxybenzamine hydrochloride (Dibenzyline)
This is a long-acting adrenergic alpha-receptor blocker that can produce and maintain a chemical sympathectomy. Phenoxybenzamine lowers supine and upright blood pressure. It does not affect the parasympathetic nervous system. Reflex tachycardia is a concern and may require the addition of a beta blocker.
Phentolamine mesylate (OraVerse)
Phentolamine mesylate is a nonselective alpha-adrenergic blocking agent that produces transient and incomplete alpha-adrenergic blockade. This agent is often used immediately before or during adrenalectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. It is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on alpha receptors.
Prazosin (Minipress, Prazin, Prazo)
Prazosin is a quinazoline compound that is a selective alpha1 adrenergic antagonist. Prazosin causes peripheral vasodilation by selective, competitive inhibition of vascular postsynaptic alpha1-adrenergic receptors, thus reducing peripheral vascular resistance and blood pressure.
Terazosin (Hytrin)
Terazosin is a quinazoline compound that is a a selective alpha1 adrenergic antagonist. Terazosin causes peripheral vasodilation by selective, competitive inhibition of vascular postsynaptic alpha1-adrenergic receptors, thus reducing peripheral vascular resistance and blood pressure.
BPH, Alpha Blocker
Doxazosin mesylate (Cardura, Cardura XL)
Doxazosin mesylate is a quinazoline compound that is a selective alpha1-adrenergic antagonist. It inhibits postsynaptic alpha-adrenergic receptors, resulting in the vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure.
Vasodilators
Nitroprusside sodium (Nipride, Nitropress, Sodium Nitroprusside)
Nitroprusside is a direct vasodilator that relaxes arterial vessels and venous smooth muscle. It has a short half-life and its effect disappears within 5 minutes of stopping infusion. The drug may be used to control paroxysmal hypertension intraoperatively. Nitroprusside produces vasodilation and increases the inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing the heart rate.
Beta Blockers, Nonselective
Propranolol (Inderal LA, InnoPran XL)
Propranolol is a nonselective beta-adrenergic receptor blocker. The drug has membrane-stabilizing activity and decreases the automaticity of contractions.
After primary treatment with an alpha receptor blocker, propranolol may be used as adjunctive therapy if control of tachycardia becomes necessary before or during surgery. It may be used to treat excessive beta receptor stimulation in patients with inoperable metastatic pheochromocytoma. Propranolol is not suitable for the emergency treatment of hypertension; do not administer it intravenously in hypertensive emergencies.
Beta Blockers, Beta1 Selective
Atenolol (Tenormin)
Atenolol selectively blocks beta1 (cardioselective) receptors, with little or no effect on beta2 types. After primary treatment with an alpha receptor blocker, atenolol may be used as adjunctive therapy if control of tachycardia becomes necessary before or during surgery.
Metoprolol (Lopressor)
Metoprolol selectively blocks beta1 (cardioselective) receptors, with little or no effect on beta2 types at low doses. However, at higher plasma concentrations, metoprolol also inhibits beta2 receptors. After primary treatment with an alpha receptor blocker, metoprolol may be used as adjunctive therapy if control of tachycardia becomes necessary before or during surgery.
Esmolol (Brevibloc)
Esmolol is a short-acting beta1 selective beta blocker administered via continuous intravenous infusion. In low doses, esmolol selectively blocks sympathetic stimulation mediated by beta1-adrenergic receptors in the heart and vascular smooth muscle. Esmolol's extremely short duration of action makes the drug useful for acute control of hypertension or certain supraventricular arrhythmias.
Antihypertensives, Other
Metyrosine (Demser)
Metyrosine inhibits tyrosine hydroxylase, the rate-limiting step in catecholamine synthesis. In patients with pheochromocytoma, administration of metyrosine reduces catecholamine biosynthesis by 35-80%, as measured by urinary catecholamine levels.
Metyrosine is indicated in patients with pheochomocytoma who are awaiting surgery, for long-term management of patients with malignant pheochromocytoma, or in cases of pheochromocytoma in which surgery is contraindicated. It can be useful in patients whose condition is refractory to phenoxybenzamine therapy, or it can be administered as an adjunct to that therapy.
Radiopharmaceuticals
Class Summary
Iobenguane I 131 is the first drug approved by the FDA for pheochromocytomas or paragangliomas that cannot be removed by surgery.
Iobenguane I 131 (Azedra)
Iobenguane is similar in structure to the neurotransmitter norepinephrine (NE) and is subject to the same uptake and accumulation pathways as NE. Iobenguane is taken up by the NE transporter in adrenergic nerve terminals and accumulates in adrenergically innervated tissues (eg, heart, lungs, adrenal medulla, salivary glands, liver, spleen), as well as in tumors of neural crest origin. Following intravenous (IV) administration and cell uptake, radiation resulting from radioactive decay of I 131 causes cell death and tumor necrosis.
Iobenguane I 131 is indicated in adults and children aged 12 years or older when systemic anticancer therapy is needed for iobenguane scan–positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma.
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Axial, T2-weighted magnetic resonance imaging (MRI) scan showing large left suprarenal mass of high signal intensity on a T2-weighted image. The mass is a pheochromocytoma.
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Abdominal computed tomography (CT) scan demonstrating left suprarenal mass of soft-tissue attenuation representing a paraganglioma.
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Adrenalectomy specimen containing pheochromocytoma. Non-neoplastic adrenal cortex (yellow) surrounds a small tan-red tumor in the medullary region, representing a pheochromocytoma.
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H and E, high power, showing classic "balls of cells" feature of a pheochromocytoma. Endocrine tumors such as a pheochromocytoma typically show some degree of nuclear pleomorphism ("endocrine atypia") which does not indicate malignancy.
