What is the use and dosage of prazosin in treating hypertension and benign prostatic hyperplasia?

Prazosin for Hypertension and Benign Prostatic Hyperplasia

Prazosin is no longer considered a first-line agent for either hypertension or benign prostatic hyperplasia (BPH), as newer alpha-blockers with more favorable dosing schedules and side effect profiles have largely replaced it in clinical practice. 1

Mechanism of Action

Prazosin is a selective alpha-1 adrenergic receptor antagonist that works by:

• Inhibiting alpha-1 adrenergic-mediated contraction of vascular smooth muscle, reducing peripheral vascular resistance in hypertension
• Blocking alpha-1 receptors in prostatic smooth muscle, reducing prostatic tone and relieving bladder outlet obstruction in BPH 2

Use in Benign Prostatic Hyperplasia

Efficacy

• Studies show prazosin can improve BPH symptoms in 60-70% of patients 2
• Provides improvement in:
  • Urinary flow rates
  • Decreased urethral pressure
  • Reduction in obstructive and irritative symptoms 3

Dosing for BPH

• Initial: 0.5 mg twice daily for 4 days
• Titration: 1 mg twice daily for 4 days
• Maintenance: 2 mg twice daily 3

Current Status in BPH Treatment

While prazosin was one of the earlier alpha blockers used for BPH, current guidelines from the European Association of Urology and American Urological Association recommend newer agents like alfuzosin, tamsulosin, or silodosin as first-line alpha blockers for BPH due to:

• More convenient once-daily dosing
• Fewer vasodilatory side effects
• Similar or better efficacy profiles 1

Use in Hypertension

Prazosin was historically used for hypertension but has been largely replaced by:

• Longer-acting alpha blockers (doxazosin)
• Other antihypertensive classes with better evidence for cardiovascular outcomes

Historical Dosing for Hypertension

• Initial: 1 mg two to three times daily
• Maintenance: 6-15 mg daily in divided doses 4

Side Effects and Precautions

Common Side Effects

• First-dose phenomenon (severe hypotension, syncope)
• Orthostatic hypotension
• Dizziness
• Headache
• Drowsiness
• Nasal congestion 4

Important Precautions

• First dose should be taken at bedtime to minimize risk of syncope
• Patients with moderate to severe hepatic impairment should avoid alpha blockers 1
• Concomitant use with potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) should be avoided 1
• Can cause intraoperative floppy iris syndrome during cataract surgery 5

Comparative Efficacy

A randomized multicenter study comparing prazosin, terazosin, and tamsulosin for BPH found:

• Prazosin (5 mg/day) improved total symptom score by 38% at 4 weeks
• Terazosin showed significantly higher improvement in individual symptoms compared to tamsulosin
• Prazosin significantly increased maximum urinary flow rate
• Blood pressure decreased significantly in hypertensive patients taking prazosin 6

Current Treatment Recommendations

For BPH:

• Alpha blockers are recommended as first-line treatment for moderate to severe LUTS due to BPH 1
• Newer uroselective alpha blockers (tamsulosin, silodosin) or long-acting agents (alfuzosin) are preferred over prazosin due to better tolerability and once-daily dosing 1
• For patients with larger prostates (>30cc), combination therapy with an alpha blocker plus 5-alpha-reductase inhibitor is recommended 1

For Hypertension:

• Prazosin is not recommended as first-line therapy for hypertension according to current guidelines
• When treating a patient with both hypertension and BPH, using an alpha blocker for BPH should not be assumed to constitute optimal management of hypertension 1

Practical Considerations

• Start with low doses to minimize first-dose hypotension
• Monitor for orthostatic hypotension, especially in elderly patients
• Inform patients taking alpha blockers to alert their ophthalmologist before cataract surgery
• Consider newer alpha blockers with more favorable dosing schedules and side effect profiles for both conditions