PRAZOSIN HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Prazosin is a quinazoline derivative that acts as a selective, competitive antagonist at postsynaptic alpha-1 adrenergic receptors. It blocks the binding of norepinephrine, thereby inhibiting vasoconstriction and reducing peripheral vascular resistance, leading to decreased blood pressure. It also relaxes smooth muscle in the prostate and bladder neck, improving urine flow. Additionally, it may block alpha-1 receptors in the central nervous system, reducing sympathetic outflow and ameliorating nightmare-related symptoms in PTSD.
| Metabolism | Extensively metabolized in the liver primarily via CYP3A4, with minor contributions from CYP2C9 and CYP2D6. Major metabolites include prazosin glucuronide and 4-amino-6,7-dimethoxy-2-(1-piperazinyl)quinazoline. Oral bioavailability is about 48-68% due to first-pass metabolism. |
| Excretion | Primarily hepatic metabolism (demethylation and conjugation); <10% unchanged in urine; 90% eliminated via bile/feces. |
| Half-life | Terminal elimination half-life: 2-3 hours. However, antihypertensive effect persists for up to 24 hours due to prolonged receptor binding, allowing once-daily dosing. |
| Protein binding | 97% bound to plasma proteins, primarily alpha-1 acid glycoprotein. |
| Volume of Distribution | 0.6 L/kg, indicating extensive distribution into total body water and tissue binding. |
| Bioavailability | Oral bioavailability: 60% (first-pass hepatic metabolism). |
| Onset of Action | Oral: 1-2 hours (first-dose syncope may occur within 30-90 minutes with initial dose). |
| Duration of Action | Antihypertensive effect persists for 10-24 hours. Maximal reduction in blood pressure occurs at 2-4 hours post-dose. Duration of action may increase with chronic dosing. |
1 mg orally 2-3 times daily, titrated up to 20 mg/day in divided doses for hypertension; for benign prostatic hyperplasia, 0.5-1 mg orally twice daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate impairment (GFR >30 mL/min). For severe impairment (GFR <30 mL/min), start with 0.5 mg orally twice daily and titrate cautiously. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce starting dose by 50% (0.5 mg twice daily). Class C: avoid use or start at 0.5 mg once daily with slow titration. |
| Pediatric use | Hypertension: 0.05-0.1 mg/kg/day orally in 2-3 divided doses, titrated up to 0.5 mg/kg/day. Maximum 20 mg/day. |
| Geriatric use | Start at 0.5 mg orally twice daily due to increased sensitivity and risk of orthostatic hypotension; titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other antihypertensive drugs can have additive effects Can cause marked first-dose hypotension and syncope.
| Breastfeeding | Prazosin is excreted into human milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.15-0.20. The estimated infant dose is <1% of the maternal weight-adjusted dose. American Academy of Pediatrics considers prazosin compatible with breastfeeding. However, caution in preterm or low-birth-weight infants due to immature drug clearance. Observe for signs of hypotension, sleepiness, or feeding difficulties. |
| Teratogenic Risk | Prazosin hydrochloride is classified as FDA Pregnancy Category C. In animal studies, no teratogenic effects were observed at doses up to 30 times the human dose. However, decreased fetal survival occurred in rats and rabbits. There are no adequate and well-controlled studies in pregnant women. First trimester: Risk cannot be ruled out; use only if potential benefit justifies potential risk to the fetus. Second and third trimesters: Limited data; possible risk of fetal hypotension, hypoxia, or reduced placental perfusion due to alpha-blockade. Monitor fetal heart rate and growth if used near term. |
■ FDA Black Box Warning
None
| Common Effects | BPH |
| Serious Effects |
Hypersensitivity to prazosin or any component of the formulation. Concurrent use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of severe hypotension.
| Precautions | First-dose syncope (marked hypotension within 30-90 minutes of initial dose or dose increase). Orthostatic hypotension and syncope, especially with rapid dose escalation. Avoid abrupt discontinuation to prevent rebound hypertension. Use with caution in patients with hepatic impairment, chronic kidney disease, heart failure with reduced ejection fraction, and concurrent use with phosphodiesterase-5 inhibitors (e.g., sildenafil) due to additive hypotension. May cause priapism, intraoperative floppy iris syndrome during cataract surgery, and exacerbation of angina in patients with coronary artery disease. |
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| Fetal Monitoring | Maternal: Blood pressure and heart rate monitoring at baseline and regularly during therapy. Assess for orthostatic hypotension, especially after first dose. Renal function and electrolytes periodically. Fetal: Ultrasound monitoring for growth, amniotic fluid volume, and non-stress test or biophysical profile as clinically indicated, especially if preeclampsia is present. Neonatal: Observe for hypotension, lethargy, and poor feeding after delivery. |
| Fertility Effects | No specific human studies on fertility. In animal reproductive studies, no adverse effects on mating or fertility were observed at clinically relevant doses. However, alpha-blockers may affect ejaculatory function in males (e.g., reduced or absent ejaculation). In females, theoretical risk of uterine relaxation due to alpha-blockade, but not established. Use in women of childbearing age requires careful consideration of potential impact on fertility. |