Prazocin

Alpha-adrenergic antagonist (alpha-blocker) Therapeutic Category: Antihypertensive, Agent for Benign Prostatic Hyperplasia, Agent for PTSD Nightmares

Prazosin selectively inhibits postsynaptic alpha-1 adrenergic receptors. These receptors are located on vascular smooth muscle. By blocking the binding of norepinephrine to these receptors, prazosin prevents the vasoconstrictive effects of norepinephrine. This leads to vasodilation of both arterial and venous blood vessels, resulting in a decrease in peripheral vascular resistance and a reduction in blood pressure. In the prostate and bladder neck, alpha-1 receptors are also present and contribute to smooth muscle tone; blockade of these receptors leads to relaxation, relieving obstruction and improving urinary flow in patients with BPH. The mechanism by which prazosin reduces PTSD-related nightmares is less well-defined but is thought to involve modulation of the noradrenergic system and its role in fear conditioning and sleep architecture.

Absorption: Prazosin is well absorbed from the gastrointestinal tract following oral administration. The bioavailability is approximately 80-100%. Peak plasma concentrations are typically achieved within 1 to 4 hours after a dose. Distribution: Prazosin is moderately bound to plasma proteins, approximately 70-80%. It has a relatively large volume of distribution, indicating significant distribution into tissues. Metabolism: Prazosin undergoes hepatic metabolism, primarily through O-demethylation and hydroxylation. The major active metabolite is 6-hydroxy prazosin, which has some alpha-blocking activity, but it is significantly less potent than the parent drug. Excretion: Prazosin and its metabolites are excreted in both urine and feces. Approximately 60% of the dose is excreted in urine, with about 10% as unchanged drug. The remaining 35-40% is excreted in feces. Half-life: The elimination half-life of prazosin is approximately 2-3 hours in healthy individuals. This half-life can be prolonged in patients with renal impairment.

Prazosin exerts its effects by blocking alpha-1 adrenergic receptors. This blockade leads to: • Vasodilation: Relaxation of smooth muscle in blood vessels, decreasing peripheral vascular resistance and lowering blood pressure. • Reduced preload and afterload: Decreased venous tone reduces the workload on the heart. • Improved urinary flow: Relaxation of smooth muscle in the prostate and bladder neck, facilitating urination in BPH. • Modulation of sleep and arousal: May influence noradrenergic pathways involved in sleep regulation, potentially reducing nightmares.

• Hypertension: Prazosin is indicated for the treatment of hypertension. It can be used alone or in combination with other antihypertensive agents. • Benign Prostatic Hyperplasia (BPH): Prazosin is indicated for the symptomatic treatment of BPH. It helps to improve urine flow and reduce symptoms associated with an enlarged prostate. • Post-Traumatic Stress Disorder (PTSD) Nightmares: Prazosin is used off-label to reduce the frequency and intensity of nightmares associated with PTSD.

Absolute: • Known hypersensitivity to prazosin or other quinazoline derivatives. Relative: • Patients with a history of syncope with alpha-blocker therapy. • Patients with severe cardiovascular disease. • Patients with hepatic impairment (caution advised due to hepatic metabolism).

Hypertension: Initial dose: 1 mg two or three times daily. Maintenance dose: Typically 6-10 mg daily in two or three divided doses. Doses may range from 1 mg to 20 mg daily, depending on patient response and tolerance. The dose should be titrated gradually. Benign Prostatic Hyperplasia (BPH): Initial dose: 1 mg at bedtime. Maintenance dose: 1 mg to 2 mg twice daily, or 2 mg at bedtime. Maximum recommended dose is 6 mg daily in divided doses. Post-Traumatic Stress Disorder (PTSD) Nightmares: Initial dose: 1 mg at bedtime. Maintenance dose: Doses typically range from 1 mg to 8 mg at bedtime, with gradual titration based on patient response and tolerability. Doses may be adjusted by the prescribing physician.

Pediatric: Safety and efficacy have not been established in pediatric patients. Geriatric: Elderly patients may be more sensitive to the hypotensive effects of prazosin, particularly orthostatic hypotension. Lower starting doses and slower titration are recommended. Monitor blood pressure closely. Renal impairment: Prazosin is excreted by the kidneys. In patients with severe renal impairment (creatinine clearance <10 mL/min), the half-life may be prolonged. Dosage reduction may be necessary, and careful monitoring of blood pressure and adverse effects is recommended. Hepatic impairment: Prazosin is metabolized in the liver. Patients with hepatic impairment may have reduced clearance of the drug. Caution should be exercised, and lower doses may be considered. Monitor liver function tests if clinically indicated.

Common (>10%): • Dizziness • Headache • Drowsiness • Nausea • Palpitations • Weakness Serious (<1%): • Orthostatic hypotension (especially with the first dose or dose increase) leading to syncope. • Priapism (persistent, painful erection). • Lupus-like syndrome. • Bronchospasm. • Edema. • Visual disturbances. • Severe allergic reactions (anaphylaxis).

• Other antihypertensive agents (e.g., diuretics, beta-blockers, calcium channel blockers): Additive hypotensive effects, increasing the risk of orthostatic hypotension. • Beta-blockers: May enhance the hypotensive effect, but also may mask reflex tachycardia associated with prazosin. • Diuretics: Additive hypotensive effects. Careful monitoring of electrolytes and blood pressure is recommended. • Phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil): Increased risk of symptomatic hypotension. Coadministration should be approached with caution, and patients should be advised to avoid PDE5 inhibitors if they have experienced syncope with prazosin. • Vasodilators: Additive hypotensive effects.

• First-dose phenomenon: A significant drop in blood pressure, dizziness, and syncope can occur within 30 to 90 minutes of the first dose or with subsequent increases in dosage. Patients should be advised to take the first dose at bedtime and to avoid driving or operating machinery until they know how the drug affects them. • Orthostatic hypotension: Prazosin can cause orthostatic hypotension, especially during dose titration or in patients with underlying cardiovascular disease. Patients should be advised to rise slowly from a sitting or lying position. • Syncope: Patients who experience syncope should be advised to discontinue the drug and consult their physician. • Fluid retention: Prazosin can cause fluid retention and edema. This may be more pronounced in patients with heart failure. Diuretics may be necessary to manage this side effect. • Intraoperative Floppy Iris Syndrome (IFIS): IFIS has been observed during cataract surgery in some patients taking or who have previously taken alpha-1 blockers, including prazosin. Surgeons should be aware of this potential complication.

Pregnancy: Pregnancy Category C. Prazosin has shown some evidence of adverse effects in animals, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation: Prazosin is excreted in breast milk in small amounts. Caution should be exercised when prazosin is administered to a nursing woman. The decision to continue or discontinue breastfeeding should be made based on the importance of the drug to the mother.

• Blood pressure: Monitor blood pressure regularly, especially during initiation of therapy and after dose adjustments. This includes monitoring for orthostatic hypotension. • Renal function: Periodic assessment of renal function, especially in patients with pre-existing renal impairment or those on concurrent nephrotoxic medications. • Liver function: Periodic assessment of liver function, particularly in patients with known hepatic impairment or those on long-term therapy. • Electrolytes: Monitor electrolytes, especially when used in combination with diuretics.

• Take prazosin exactly as prescribed by your doctor. • Take the first dose at bedtime to minimize the risk of dizziness and fainting. • Rise slowly from a sitting or lying position to avoid dizziness and lightheadedness. • Avoid driving or operating heavy machinery until you know how prazosin affects you. • Do not stop taking prazosin without consulting your doctor, as this can cause your blood pressure to rise. • Inform your doctor about all other medications you are taking, including over-the-counter drugs and herbal supplements. • Report any unusual side effects to your doctor, especially dizziness, fainting, or a prolonged erection (priapism). • If you are scheduled for cataract surgery, inform your eye doctor that you are taking prazosin, as it can affect the procedure (Intraoperative Floppy Iris Syndrome).

Store at room temperature (20°C to 25°C or 68°F to 77°F). Protect from light and moisture. Keep out of reach of children.

• For hypertension, consider initiating prazosin at bedtime due to the risk of orthostatic hypotension with the first dose. • In BPH, prazosin can be particularly useful for patients who also have hypertension, providing a dual therapeutic benefit. • For PTSD nightmares, the therapeutic effect may take several weeks to become apparent, and consistent dosing is important. • Prazosin's relatively short half-life necessitates divided dosing for sustained blood pressure control in hypertension. • Be aware of the potential for drug interactions, especially with other hypotensive agents and PDE5 inhibitors.

• United States Pharmacopeia (USP) Drug Information. Prazosin. • Lexicomp Online. Prazosin: Drug Information. • UpToDate. Prazosin: Drug information.