MINISON 1MG TABLET

Indications

• Hypertension
• Benign prostatic hyperplasia
• Post-traumatic stress disorder (PTSD) related sleep disturbances

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: Initially 500 micrograms 2–3 times a day for 3–7 days, taken at bedtime. Maintenance doses can be increased to 4–20 mg daily in divided doses as needed.

Mechanism of action

Prazosin selectively inhibits postsynaptic alpha-1 adrenergic receptors located in vascular smooth muscle. This inhibition blocks the vasoconstricting effect of catecholamines (epinephrine and norepinephrine), resulting in peripheral blood vessel dilation and a consequent decrease in blood pressure.

Pharmacodynamics

Prazosin leads to a decrease in blood pressure, cardiac output, heart rate, and renal blood flow, including glomerular filtration rate. The drug promotes vasodilation, which decreases peripheral resistance, thus lowering blood pressure. Additionally, prazosin has shown potential benefits in alleviating sleep disturbances associated with PTSD by reducing adrenergic stimulation during hyperarousal.

Pharmacokinetics

Prazosin is absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 3 hours post-administration. The drug undergoes extensive first-pass metabolism in the liver, leading to a bioavailability of around 50%. It is primarily metabolized by cytochrome P450 enzymes, notably CYP3A4, and eliminated through urine as both unchanged drug and metabolites. The half-life of prazosin ranges from 2 to 3 hours, although the therapeutic effects can last longer due to its pharmacodynamic properties.

Contra-indications

• History of micturition syncope
• History of postural hypotension
• Congestive heart failure due to mechanical obstruction (e.g., aortic stenosis)

Adverse effects

• Asthenia
• Constipation
• Dizziness
• Fatigue
• Headache
• Nausea
• Palpitations
• Postural hypotension
• Sexual dysfunction
• Syncope
• Urinary disorders
• Vertigo
• Vision blurred
• Vomiting

Interactions

• Caution with concomitant antihypertensives
• Potentially increased risk of hypotensive effects when used with other antihypertensives

Precautions

• Care with initial dose due to risk of postural hypotension
• Elderly patients may require reduced dosage and specialist supervision
• Risk of intra-operative floppy iris syndrome during cataract surgery

Pregnancy

No evidence of teratogenicity; manufacturers advise use only when potential benefit outweighs risk.

Breast-feeding

Present in milk, amount probably too small to be harmful; manufacturer advises use with caution.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Prazosin hydrochloride 2 mg tablets (Minipress)

Mechanism of action

Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha 1 and alpha 2, both play a role in regulating blood pressure. Alpha-1 receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle. These receptors, when activated, increase blood pressure. Prazosin inhibits the postsynaptic alpha-1 adrenoceptors. This inhibition blocks the vasoconstricting (narrowing) effect of catecholamines (epinephrine and norepinephrine) on the vessels, leading to peripheral blood vessel dilation. Through blood vessel constriction by adrenergic receptor activation, epinephrine and norepinephrine normally act to increase blood pressure.

Pharmacodynamics

**Effects on blood pressure** The pharmacodynamic and therapeutic effect of this drug includes is a decrease in blood pressure as well as clinically significant decreases in cardiac output, heart rate, blood flow to the kidney, and glomerular filtration rate. The decrease in blood pressure may occur in both standing and supine positions. Many of the above effects are due to vasodilation of blood vessels caused by prazosin, resulting in decreased peripheral resistance,. Peripheral resistance refers to the level resistance of the blood vessels to blood that flows through them. As the blood vessels constrict (narrow), the resistance increases and as they dilate (widen), and peripheral resistance decreases, lowering blood pressure. **Effects on sleep disturbance related to post-traumatic stress disorder (PTSD)** Some studies have suggested that this drug improves sleep in patients suffering from insomnia related to nightmares and post-traumatic stress disorder, caused by hyperarousal. This effect likely occurs through the inhibition of adrenergic stimulation found in states of hyperarousal.