Introduction
Prazosin is a drug used to treat hypertension. It belongs to the class of drugs known as alpha-1 antagonists.
Recently, many studies have evaluated the benefits of this drug in controlling the symptoms of post-traumatic stress disorder (PTSD) and associated nightmares .
Uses
Prazosin is an alpha-blocker that causes a decrease in total peripheral resistance and is used to treat hypertension.
This drug is indicated for the treatment of hypertension (high blood pressure). Prazosin can be given alone or given with other blood pressure-lowering drugs, including diuretics or beta-adrenergic blocking agents .
Prazosin does not negatively impact lung function, and therefore may be used to manage hypertension in patients who are asthmatic or patients with chronic obstructive lung disease (COPD).
Associated Conditions
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 .
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 .
Absorption
After administration of an oral dose, peak plasma concentrations are attained at approximately 3 hours . There is a linear association between the prazosin dose given and plasma concentration at steady state .
Volume of Distribution
About 0.6 L/kg .
Protein Binding
Highly bound to proteins with 97% binding to albumin and alpha 1-acid glycoprotein . Prazosin is thought to be mostly (about 80-90%) bound to albumin .
Route of Elimination
This drug is mainly excreted in the bile and the feces .
Half Life
The plasma half-life is about 2-3 hours .
Clearance
In patients with congestive heart failure, the clearance of this drug is decreased. Impairment of renal function does not have relevant effects on elimination .
Toxicity
TDLO, LD50: Oral TDLO (human): 285 μg/kg; Oral TDLO (woman): 10 μg/kg .
Oral LD50 (rat): 1950 mg/kg; Intraperitoneal LD50 (rat): 102 mg/kg .
Overdose information
Accidental ingestion of at least 50 mg of prazosin by a two-year-old child led to severe drowsiness with depressed reflexes. There was no fall in blood pressure, and the child recovered without complication .
Use in pregnancy
There are no adequate and well-controlled studies determining the safety of prazosin use during pregnancy. It is considered a pregnancy category C drug. Prazosin should be used during pregnancy only in cases where the benefit outweighs the possible risk to the mother and fetus . In specific cases where blood pressure control was emergent during pregnancy, prazosin has been used and no effects on the fetus or neonate were reported .
Use in nursing
This drug is found excreted in small concentrations in human milk. This drug should be used with caution when used during nursing .
Food Interactions
- Avoid alcohol.
- Avoid natural licorice.
- Take with or without food. The absorption is unaffected by food.
Dosage
- Hypertension: For maximum benefit, small increases should be continued until the desired effect is achieved or a total daily dosage of 20 mg is reached. A diuretic or adrenergic beta-blocking agent may be added to enhance efficacy. The maintenance dosage of Prazosin may be given as a twice or three times daily regimen.
- Patients Receiving No Antihypertensive Therapy. It is recommended that therapy be initiated with 0.5 mg given in the evening at bedtime then 0.5 mg b.i.d. or t.i.d for three to seven days. Unless poor toleration suggests the patient is unusually sensitive, this dosage should be increased to 1 mg given b.i.d. or t.i.d. for a further three to seven days. Thereafter, as determined by the patient's response to the blood pressure lowering effect, the dosage should be increased gradually to a total daily dosage of 20 mg given in divided doses.
- Patients Receiving Diuretic Therapy With inadequate Control of Blood Pressure. The diuretic should be reduced to a maintenance dosage level for the particular agent and Prazosin initiated with 0.5 mg h.s then proceeding to 0.5 mg b.i.d or t.i.d. After the initial period of observation, the dosage of Prazosin should be gradually increased as determined by the patient's response.
- Patients Receiving Other Antihypertensives But With Inadequate Control. Because some additive effect is anticipated, the other agent dosage level (e.g. beta-adrenergic blocking agents, methyldopa. reserpine, lsnidine etc.) should be reduced and Prazosin initiated at 0.5 mg h.s. then proceeding to 0.5 mg b.i.d, or t.i.d. Subsequent dosage increase should be made depending upon the patient's response. There is evidence that adding Prazosin to beta-adrenergic blocking agents, calcium antagonists or ACE inhibitors may bring about a substantial reduction in blood pressure. Thus, to low initial dosage regimen is strong, recommended.
- Patients With Moderate to Severe Grades of Renal Impairment Evidence to date shows that Prazosin does not further compromise renal function when used in patients with renal impairment. Because some patients in this category have responded to small doses of Prazosin , it is recommended that therapy be initiated at 0.5 mg daily and that dosage increases be instituted cautiously.
Suggested Starting Dosage: 0.5 mg b.i.d., t.i.d. or q.i.d. increasing to 4 mg in divided doses.
Use Daily Maintenance Dosage: 4 mg once daily to 20 mg in divided doses.
Raynaud's Phenomenon And Raynaud's Disease: The recommended starting dosage is 0.5 mg b.i.d. given for a period of three to seven days. Dosage should be adjusted according to the patient's clinical response.
Suggested Starting Dosage: 0.5mg b.i.d.
Usual Daily Maintenance Dosage: 1mg or 2 mg b.i.d Doses up to 2 mg t.i.d. may be required for some patients.
Benign Prostatic Hyperplasia: The recommended starting dose is 0.5 mg twice daily given for a period of 3 to 7 days and should then be adjusted according to the patient's clinical responses. The usual maintenance dose is 2 mg twice daily. The safety and efficacy of a total daily dosage greater than 4 mg have not been established. Therefore, total daily dosages greater than 4mg should be used with caution.
Prazosin XR Tablet: Prazosin XR Extended-Release Tablets must be swallowed whole and should not be bitten or divided. Therapy for hypertension with Prazosin XR must be initiated at 2.5 mg once daily. The 5 mg dosage form of Prazosin XR is not for initial dosing. Dosage may be increased slowly, in general over a 7 to 14-day period, depending on the response to each dose level. Doses above 20 mg once daily have not been studied.
Maintenance Dose: Dosage may be increased as clinically indicated to 20 mg given in once-daily doses.
Hypertensive patients controlled on Prazosin Tablets alone or in combination with other antihypertensive medications may be switched to Prazosin XR Extended Release Tablets at the equivalent or nearest higher total daily dose, e.g. Prazosin Tablets 4 mg daily equivalent to Prazosin XR Extended Release Tablets 5 mg once daily. Blood pressure measurements should be taken at the end of the dosing interval to assure adequate blood pressure control is maintained throughout the 24-hour period. Further titration may be necessary in some patients.
The addition of a diuretic or other antihypertensive agent to prazosin has been shown to cause an additive hypotensive effect.
