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Phenoxybenzamine (Dibenzyline)

Dibenzyline

Non-competitive irreversible alpha-1 + alpha-2 antagonist

IRREVERSIBLE non-competitive antagonist at alpha-1 + alpha-2 adrenergic receptors. Covalently binds + permanently inactivates receptors — duration of action depends on receptor RESYNTHESIS (24-48 h after each dose). Distinguishes from competitive antagonists (phentolamine) where catecholamine surge can overcome blockade.

Indications

  • Pheochromocytoma — preoperative alpha blockade (preferred over selective α1 like prazosin in many centers — though doxazosin/prazosin also acceptable per Endocrine Society 2014)
  • Neurogenic bladder hypertonia (off-label)
  • Raynaud phenomenon (rarely used)

Dosing

ContextAdultPediatric
Pheo preop alpha blockade10 mg PO BID, increase by 10-20 mg/day every 2-3 days; titrate to mild postural hypotension + nasal stuffiness + target HR 70-80 sitting; typical effective 40-100 mg/day; START ≥7-14 days preop

Pharmacokinetics

Onset 2 h. Duration of effect 24-48 h per dose (irreversible — depends on receptor resynthesis). Hepatic metabolism.

Hemodynamic effects

↓BP (especially upright — postural hypotension common + intentional). Reflex tachycardia. After alpha blockade established → liberal salt + fluid → 'fill the contracted intravascular space' before surgery.

Side effects

  • !Postural hypotension (intended endpoint of titration)
  • !Reflex tachycardia (add beta-blocker AFTER alpha block established — never before)
  • !Nasal congestion
  • !Sedation
  • !Inhibition of ejaculation
  • !Miosis

Contraindications

  • ×Hypersensitivity
  • ×Active hypotension

Clinical pearls

  • PHEO PROTOCOL: alpha blockade ≥7-14 days preop (target endpoints: orthostatic hypotension + nasal congestion + target HR sitting); LIBERAL SALT + FLUID intake (counters volume contraction); ADD BETA-BLOCKADE only AFTER alpha (unopposed beta + intact alpha = severe HTN crisis + reflex bradycardia + arrest).
  • ALTERNATIVE: doxazosin or prazosin (selective α1, competitive — easier titration but possibly less reliable blockade for surgery — Endocrine Society 2014 considers both acceptable).
  • Postop: profound hypotension common after tumor removal (catecholamine drop + persistent alpha blockade) — vasopressor + volume support.
  • DO NOT discontinue suddenly — wean over 1-2 weeks once tumor removed + recovery established.
Education only — confirm against current package inserts and institutional protocols. Doses assume normal organ function unless otherwise noted.