Prazosin - Drug Monograph

Introduction

Prazosin is a quinazoline derivative that serves as a selective alpha-1 adrenergic receptor antagonist. First approved by the FDA in 1976, it was among the earliest antihypertensive medications developed that specifically targeted peripheral alpha-adrenergic receptors. While initially developed for hypertension management, prazosin has gained significant clinical importance for its off-label uses, particularly in treating post-traumatic stress disorder (PTSD)-associated nightmares and benign prostatic hyperplasia (BPH).

Mechanism of Action

Prazosin exerts its pharmacological effects through competitive blockade of postsynaptic alpha-1 adrenergic receptors. This selective inhibition prevents norepinephrine from binding to these receptors, resulting in:

• Vasodilation of both arterial and venous vascular beds
• Reduction in peripheral vascular resistance
• Decreased smooth muscle tone in the prostate and bladder neck
• Modulation of central nervous system adrenergic activity

Unlike non-selective alpha blockers, prazosin has minimal effect on alpha-2 receptors, which preserves negative feedback mechanisms and reduces the risk of tachycardia.

Indications

• Hypertension (as monotherapy or in combination with other antihypertensive agents)

• Post-traumatic stress disorder (PTSD)-associated nightmares and sleep disturbances
• Benign prostatic hyperplasia (BPH) symptoms
• Raynaud's phenomenon
• Complex regional pain syndrome
• Treatment-resistant anxiety

Dosage and Administration

• Initial dose: 1 mg orally two or three times daily
• Maintenance dose: 6-15 mg daily in divided doses (maximum 20 mg daily)
• Titration: Increase gradually over several weeks

• Starting dose: 1 mg at bedtime
• Titration: Increase by 1 mg every 3-7 days as tolerated
• Effective range: 3-15 mg at bedtime

• Initial dose: 1 mg twice daily
• Maintenance dose: 2-4 mg twice daily

• Geriatric patients: Initiate with lower doses (0.5 mg)
• Renal impairment: No specific dosage adjustment required
• Hepatic impairment: Use with caution; consider reduced dosing

Pharmacokinetics

• Oral bioavailability: Approximately 60%
• Peak plasma concentration: 2-3 hours post-administration
• Food may delay absorption but does not affect overall bioavailability

• Protein binding: 92-97%
• Volume of distribution: 0.5 L/kg
• Crosses blood-brain barrier

• Extensive hepatic metabolism via demethylation and conjugation
• Primarily via CYP3A4 enzyme system

• Half-life: 2-3 hours
• Excretion: Primarily biliary (feces) with minimal renal excretion
• Dialysis: Not effectively removed

Contraindications

• Hypersensitivity to prazosin or any component of the formulation
• Concurrent use with phosphodiesterase-5 inhibitors (in patients with hypertension)
• Orthostatic hypotension
• Mitral valve stenosis
• Left ventricular outflow obstruction

Warnings and Precautions

• Pregnancy Category C: Use only if potential benefit justifies potential risk
• Lactation: Excreted in breast milk; use with caution
• Geriatric patients: Increased sensitivity to hypotensive effects

• Intraoperative floppy iris syndrome risk during cataract surgery
• Priapism (rare but serious)
• Depression reported in some patients

Drug Interactions

• Other antihypertensive agents: Additive hypotensive effects
• Phosphodiesterase-5 inhibitors: Profound hypotension
• CYP3A4 inhibitors (ketoconazole, ritonavir): Increased prazosin levels
• CYP3A4 inducers (rifampin): Decreased prazosin efficacy

• Beta-blockers: Enhanced first-dose hypotensive effect
• Diuretics: Increased risk of volume depletion and hypotension
• NSAIDs: May reduce antihypertensive effect
• Alcohol: Enhanced hypotensive effects

Adverse Effects

• Dizziness (10-15%)
• Headache (8-10%)
• Drowsiness (7-9%)
• Lack of energy (6-8%)
• Weakness (5-7%)
• Palpitations (5-6%)

• Nausea
• Depression
• Nervousness
• Rash
• Blurred vision

• Syncope
• Orthostatic hypotension
• Priapism
• Angina exacerbation
• Hallucinations

Monitoring Parameters

• Blood pressure (standing and supine)
• Heart rate
• Renal function
• Hepatic function
• Prostate-specific antigen (if used for BPH)

• Blood pressure at each dose adjustment
• Orthostatic blood pressure checks
• Symptoms of hypotension
• Mental status changes
• Sexual function assessment
• Periodic liver function tests

Patient Education

• Take initial dose at bedtime to minimize first-dose effects
• Rise slowly from sitting or lying positions
• Avoid driving or hazardous activities until response is known
• Do not abruptly discontinue medication
• Report dizziness, fainting, or prolonged erection immediately
• Limit alcohol consumption
• Be consistent with timing of doses

• Take with or without food consistently
• If missing a dose, take as soon as remembered unless close to next dose
• Do not double doses

• Maintain adequate fluid intake
• Avoid excessive heat exposure
• Be cautious with activities that may cause dehydration

References

1. FDA Prescribing Information: Minipress (Prazosin) 2. Chobanian AV, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252 3. Raskind MA, et al. A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003-1010 4. Roehrborn CG, et al. The Effects of Doxazosin, Tamsulosin and Prazosin on Blood Pressure and Symptoms in Patients with Benign Prostatic Hyperplasia. BJU Int. 2007;100(2):321-326 5. Lexicomp Online: Prazosin Monograph 6. Micromedex Solutions: Prazosin Drug Information 7. Clinical Pharmacology Database: Prazosin Pharmacokinetics