Prazosin

Reviewed and revised 7 February 2025

CLASS

• Alpha-1 adrenergic receptor antagonist (reversible)
• quinazoline derivative

MECHANISM OF ACTION

• Alpha-1 adrenergic receptor antagonist:
  • Location: Vascular smooth muscle, prostate, bladder neck. Also CNS.
  • Receptor interaction: selective, reversible binding to postsynaptic alpha-1 adrenergic receptors (α1 >>>> α2), which antagonises noradrenaline action.
  • Second messenger pathways: Inhibition of Gq protein-coupled receptor pathway leads to decreased intracellular calcium levels.
  • Pharmacodynamic effects:
    • Vasodilation (arterioles and veins), decreased peripheral resistance, decreased preload due to venodilation, reduced blood pressure
    • relaxation of bladder neck and prostate
    • lowers TAG and LDL, and increases HDL
    • effects on CNS noradrenergic pathways may modulate sleep patterns
  • Duration of action: 7-10 hours.

PHARMACEUTICS

• Oral capsules: 1 mg, 2 mg, 5 mg.

DOSE

• Hypertension:
  • Initial: 1 mg q8h.
  • Maintenance: 1-20 mg/day in divided doses.
  • Maximum: 40 mg/day.
• Benign prostatic hyperplasia (BPH):
  • Initial: 1 mg q8h.
  • Maintenance: 2-10 mg/day in divided doses.
• Post-traumatic stress disorder (PTSD):
  • Initial: 1 mg at bedtime.
  • Titrate: Increase by 1 mg every 2-3 days.
  • Typical dose: 3-15 mg/day.
• Raynaud’s syndrome:
  • Initial: 0.5 mg bd.
  • Maintenance: 1-2mg bd.

INDICATIONS

• Hypertension
  • second line treatment (agents more effective at preventing MI and stroke are generally preferred as first line)
  • useful in ICU settings for weaning from IV vasodilators and for titration of oral hypertensives
  • has been used for hypertensive toxidromes (e.g. scorpion stings, Irukandji syndrome)
• Heart failure
  • option for refractory heart failure (afterload and preload reduction)
• Benign prostatic hyperplasia (BPH)
• Post-traumatic stress disorder (PTSD): Particularly for nightmares and sleep disturbances
• Raynaud’s syndrome

CONTRAINDICATIONS

• Hypersensitivity to prazosin or other quinazolines (e.g., alfuzosin, doxazosin, terazosin)

Precautions

• Liver disease
• Cardiovascular disease (e.g. heart failure)

DRUG-DRUG INTERACTIONS

• Risk of severe hypotension in combination with other anti-hypertensives.

ADVERSE EFFECTS

• Common:
  • CNS: Dizziness, headache, drowsiness.
  • Cardiovascular: Orthostatic hypotension, palpitations
  • GI: Nausea.
• Serious:
  • Cardiovascular: Syncope, severe hypotension.
  • CNS: Depression.
  • GU: Priapism.
• Other:
  • positive test for antinuclear factor may develop (uncertain clinical significance)
  • reflex tachycardia (less common than most other vasodilators)
    

PHARMACOKINETICS

• Absorption:
  • Oral bioavailability (F): 50-70%
  • Peak plasma concentration: 1-3 hours (delayed in heart failure)
• Distribution:
  • Protein binding: 97%.
  • Volume of distribution: 0.5-1.5 L/kg.
• Metabolism:
  • Hepatic metabolism via demethylation and conjugation.
  • Major metabolites: 6-hydroxy-prazosin.
• Excretion:
  • Clearance: 10-20 L/h/70 kg
  • Renal: Only 6% of prazosin is excreted unchanged, mainly in the urine. The two main metabolites (0-demethylated) are almost completely excreted in bile.
  • Half-life: 2-3 hours.

PREGNANCY AND LACTATION

• Pregnancy:
  • Category B2 (AU).
  • Use only if potential benefit justifies potential risk.
• Lactation:
  • Excreted in breast milk.
  • Use with caution; monitor infant for adverse effects.

DOSE ADJUSTMENTS IN ORGAN FAILURES

• Renal impairment:
  • No specific dose adjustment; monitor closely.
• Hepatic impairment:
  • Use with caution; monitor closely.
• Renal replacement therapy:
  • Hemodialysis: No specific data; use with caution.

EVIDENCE

• Clinical trials:
  • Effective in reducing blood pressure in hypertensive patients.
  • Shown to improve urinary symptoms in BPH.
  • Mixed results in PTSD; some studies show benefit for nightmares.

CONTROVERSIES

• PTSD treatment: Conflicting evidence on efficacy for PTSD-related nightmares.
• First-dose effect: Significant risk of orthostatic hypotension with initial dose.

PRACTICAL TIPS

• Initiation: Start with low dose to minimize risk of orthostatic hypotension (“first dose hypotension” is common).
• Monitoring: Regularly monitor blood pressure, especially after dose adjustments.
• Administration: Take first dose at bedtime to reduce risk of syncope.

TOXICOLOGY

• Risk assessment: Risk up to 8h after ingestion, or 12h if slow release. concern if 4x times regular dose is ingested. Patient factors that increase risk: heart failure or other significant cardiovascular disease, concomitant antihypertensive use/ coingestion (e.g. beta blockers, calcium channel blockers, ACE inhibitors, sildenafil), elderly.
• Clinical features: Severe hypotension +/- shock, dizziness, fainting. Priapism can occur.
• Management:
  • Decontamination: Activated charcoal if within 1 hour of ingestion.
  • Enhanced elimination: Not effective.
  • Supportive care: IV fluids, vasopressors if needed.
  • Specific treatment: treat priapism if present and consult urology.

REFERENCES

• Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. 13th ed. New York, NY: McGraw-Hill Education; 2018.
• Jaillon P. Clinical Pharmacokinetics of Prazosin. Clin Pharmacokinet. 1980;5(4):365-376. PMID: 6994981
• Martin A, Naunton M, Kosari S, Peterson G, Thomas J, Christenson JK. Treatment Guidelines for PTSD: A Systematic Review. J Clin Med. 2021 Sep 15;10(18):4175. doi: 10.3390/jcm10184175. PMID: 34575284; PMCID: PMC8471692.
• Prazosin. Product information from TGA website [pdf]
• Vanderah, T. W., & Katzung, B. G. (2024). Katzung’s Basic and Clinical Pharmacology (16th ed.). McGraw-Hill Education.