What are the typical dosages of alpha-blockers (e.g. phenoxybenzamine, doxazosin, prazosin) and beta-blockers (e.g. propranolol) used in the management of phaeochromocytoma?

Medication Dosages for Pheochromocytoma Management

Alpha-Blockers (First-Line Preoperative Treatment)

Alpha-adrenergic blockade must be initiated at least 7-14 days before any surgical or therapeutic intervention, with gradual dose escalation until blood pressure targets are achieved: <130/80 mmHg supine AND systolic >90 mmHg standing. 1, 2

Phenoxybenzamine (Non-selective, Non-competitive Alpha Blocker)

• Starting dose: 10 mg orally twice daily 3
• Titration: Increase every other day (every 2-4 days) 1, 3
• Target dose: 20-40 mg orally 2-3 times daily 1, 3
• Mechanism advantage: Provides less intraoperative hemodynamic instability compared to selective alpha-blockers, based on the PRESCRIPT trial 1
• Key caveat: Long-term use is not recommended due to carcinogenicity concerns; causes more pronounced postoperative hypotension and side effects (orthostatic hypotension, edema, nasal congestion) 3, 4

Doxazosin (Selective Alpha-1 Blocker)

• Starting dose: Begin with low doses and titrate gradually 1
• Target dose: Titrate to blood pressure goals over 7-14 days 1
• Advantages: Fewer side effects than phenoxybenzamine, particularly less orthostatic hypotension 4
• Evidence: Equivalent perioperative safety to phenoxybenzamine in multiple studies, though may require more additional antihypertensive agents 5, 4

Prazosin (Selective Alpha-1 Blocker)

• Starting dose: 1 mg orally 2-3 times daily 6
• Titration: Increase slowly to total daily dose of 6-15 mg in divided doses 6
• Maximum dose: Up to 20-40 mg daily in divided doses if needed 6
• First-dose effect warning: Significant hypotension can occur 1-2 hours after initial dose (drops of 40-92 mmHg systolic documented); start with 1 mg and monitor closely 7
• Evidence: Effective in controlling norepinephrine-secreting pheochromocytomas when combined with beta-blockers 7

Terazosin (Selective Alpha-1 Blocker)

• Dosing: Similar approach to doxazosin and prazosin with gradual titration 1
• Usage: Listed as acceptable alternative alpha-1 blocker in guidelines 1

Beta-Blockers (Second-Line, Only After Alpha Blockade)

Critical warning: NEVER initiate beta-blockers before adequate alpha blockade—this causes hypertensive crisis from unopposed alpha-adrenergic stimulation. 1, 2, 8

Propranolol (Non-selective Beta Blocker)

• Indication: Control tachyarrhythmias after alpha blockade is established 3, 7
• Dosing: 120-480 mg daily in divided doses every 6 hours 7
• Preference note: Beta-1 selective blockers are preferred over non-selective agents 1

Esmolol (Beta-1 Selective, IV)

• Loading dose: 500-1000 mcg/kg/min over 1 minute 1
• Maintenance infusion: 50 mcg/kg/min, increase in 50 mcg/kg/min increments as needed 1
• Maximum: 200 mcg/kg/min 1
• Use: Intraoperative tachycardia control 1

Adjunctive Medications

Calcium Channel Blockers

• Indication: Adjunct to alpha-blockers for refractory hypertension OR monotherapy in patients with normal-to-mildly elevated blood pressure or severe orthostatic hypotension on alpha-blockers 1
• Example: Nifedipine slow-release formulation 1

Metyrosine

• Mechanism: Inhibits tyrosine hydroxylase, reducing catecholamine biosynthesis 1
• Use: Add-on therapy where available for additional catecholamine control 1

Acute Hypertensive Crisis Management (IV Agents)

Phentolamine (Non-selective Alpha Antagonist)

• Dose: 5 mg IV bolus 1
• Repeat: Every 10 minutes as needed 1
• Indication: Hypertensive emergencies from catecholamine excess 1

Labetalol (Combined Alpha-1 and Non-selective Beta Blocker)

• Dose: 1-2 mg/kg IV twice weekly as bolus over 1 minute, followed by continuous infusion 1
• Alternative dosing: 0.3-1.0 mg/kg (maximum 20 mg) slow IV injection every 10 minutes OR 0.4-1.0 mg/kg/h infusion up to 3 mg/kg/h 1
• Maximum cumulative dose: 300 mg, repeatable every 4-6 hours 1
• Advantage: Allows titration based on blood pressure response and avoids reflex tachycardia 1

Other IV Agents for Intraoperative Hypertension

• Magnesium sulfate, nitroprusside, nitroglycerin, or calcium antagonists can be used intraoperatively 1

Perioperative Fluid Management

• High-sodium diet and 1-2 liters of saline 24 hours before surgery to prevent postoperative hypotension 1, 2
• Compression stockings to reduce orthostatic hypotension risk 1, 2

Special Population: Dopamine-Only Producing Tumors

Do NOT use alpha-blockers for exclusively dopamine-producing pheochromocytomas (isolated plasma methoxytyramine elevation)—these patients are typically normotensive or hypotensive. 1