Prazosin

Prazosin is an Antihypertensive agent belonging to Alpha Adrenergic blockers.

Prazosin is used in the treatment of Hypertension. It is also used to treat posttraumatic stress disorder-related nightmares and sleep disruption, the Raynaud phenomenon.

The absolute bioavailability of Prazosin is 43-67%; The volume of distribution was approx 0.6 L/kg. The Plasma protein binding was >97% of Prazosin and metabolite (Prazosinat-95%). In animals, prazosin hydrochloride is heavily metabolized. This occurs through liver demethylation and conjugation Label. Some studies in humans or human cells in vitro show similar prazosin metabolism.

The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, dizziness upon standing.

Prazosin is available in the form of dosage forms, such as tablets and capsules.

Prazosin is available in the USA, Canada, Spain, France India.

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.

Prazosin is available in the form of a dosage forms, such as tablets and capsules.

Prazosin tablet is taken by mouth. It is usually taken once or twice a day with or without food.

Prazosin is used in the treatment of Hypertension. It is also used to treat posttraumatic stress disorder-related nightmares and sleep disruption, the Raynaud phenomenon.

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).

Prazosin is approved for its use in the following clinical indications:

Hypertension:

Management of Hypertension.

Although not approved, there have been certain label use documented for Prazosin which includes:

• Posttraumatic stress disorder-related nightmares
• Sleep disruption;
• Raynaud phenomenon.

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Prazosin is available in various dosage strengths: 1mg, 2mg, and 5mg.

Prazosin is available in the form of dosage forms such as tablets and capsules.

Dose Adjustment in Pediatric Patients.

Initial: 0.05-0.1 mg/kg/day taken orally divided every 8 hours.

Titrate to 0.5 mg/kg/day; not to exceed 20 mg/day

Hypertension:

Initial: 1 mg taken orally every 8 to 12 hours.

Maintenance: 6-15 mg/day divided 2 or 3 times daily; alternatively, 1-5 mg taken orally twice a day; may increase the dose to 20 mg/day in divided doses; some patients may benefit from up to 40 mg/day in divided doses

Prazosin is approved for the treatment of Hypertension.

Hypertension: It has been observed that the low-salt Dietary Approach to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

Prazosin may be contraindicated in the following.

● Hypersensitivity to Prazosin, other ACE inhibitors, or any component of the formulation; history of angioedema (with or without prior ACE inhibitor therapy); concomitant use with aliskiren in patients with diabetes mellitus; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (e.g., sacubitril).

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Concerns related to adverse effects:

• As with all alpha-blockers, Prazosin may cause syncope with sudden loss of consciousness. In most cases, this is believed to be due to an excessive postural hypotensive effect, although occasionally the syncopal episode has been preceded by a bout of severe tachycardia with heart rates of 120–160 beats per minute. Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug; occasionally, they have been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of Prazosin. The incidence of syncopal episodes is approximately 1% in patients given an initial dose of 2 mg or greater. Clinical trials conducted during the investigational phase of this drug suggest that syncopal episodes can be minimized by limiting the initial dose of the drug to 1 mg, by subsequently increasing the dosage slowly, and by introducing any additional antihypertensive drugs into the patient’s regimen with caution. Hypotension may develop in patients given Prazosin who are also receiving a beta-blocker such as propranolol.

• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with Hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use, especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure.

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.

• Diabetes: Use with caution in patients with diabetes receiving insulin or oral antidiabetic agents; may be at increased risk for episodes of hypoglycemia.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.

• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.

Special populations:

• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute.

• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent . Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible.

Other warnings/precautions:

• Appropriate use: Before taking this medicine You should not use Lotrel (combination of Amlodipine + Prazosin) if you are allergic to amlodipine or Prazosin, or if: you have had angioedema ( hives or severe swelling of deep skin tissues sometimes caused by allergic reaction).

Avoid taking alcohol with Prazosin as it may result in side effects like headache, dizziness and faintness.

Pregnancy Category C.

Prazosin has been shown to be associated with decreased litter size at birth, 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose, respectively.

The use of Prazosin and a beta-blocker for the control of severe Hypertension in 44 pregnant women revealed no drug-related fetal abnormalities or adverse effects. Therapy with Prazosin was continued for as long as 14 weeks.

Prazosin has also been used alone or in combination with other hypotensive agents in severe Hypertension of pregnancy by other investigators. No fetal or neonatal abnormalities have been reported with the use of Prazosin.

There are no adequate and well controlled studies which establish the safety of Prazosin on pregnant women. Prazosin should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Salt Substitutes: Those who are taking Prazosin should avoid sodium, calcium and magnesium-rich foods. The salts may reduce the blood-pressure lowering effect of Prazosin.

The adverse reactions related to molecule Prazosin can be categorized as

● Common Adverse effect: Cough, headache, dizziness, drowsiness

● Less Common adverse effects: Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower, hoarseness, difficulty breathing or swallowing, lightheadedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.

The clinically relevant drug interactions of Prazosin are briefly summarized here.

May cause symptomatic hypotension with phosphodiesterase type-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil).

Additive hypotensive effect with diuretics or other antihypertensive agents.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Symptoms: Hypotension

Management: Supportive treatment. Keep the patient in a supine position to restore blood pressure and normalize the heart rate. If inadequate, treat shock with volume expanders; vasopressors (including angiotensin) should be given if needed. Monitor renal function.

Pharmacodynamics:

Prazosin, a prodrug of Prazosin at, is an ACE inhibitor. It competitively inhibits the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through the angiotensin I-converting enzyme (ACE) activity, thereby reducing the levels of angiotensin II which leads to an increase in plasma renin activity and decreased aldosterone secretion.

Pharmacokinetics:

• 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.

• Distribution: Crosses the placenta (Prazosin); enters breast milk in small amounts (Prazosin and Prazosin at). Volume of distribution: Approx 0.6 L. Plasma protein binding: Approx 43-67% (Prazosin)
• Metabolism: In animals, prazosin hydrochloride is heavily metabolized. This occurs through liver demethylation and conjugation Label. Some studies in humans or human cells in vitro show similar prazosin metabolism.
• Excretion:

This drug is mainly excreted in the bile and the feces.

• https://www.mims.com/india/drug/info/Prazosin ?type=full&mtype=generic
• https://www.uptodate.com/contents/Prazosin-drug-information?search=Prazosin-drug in&usage_type=panel&kp_tab=drug_general&source=search_result&selectedTitle=1~37&display_rank=1#F162889

• https://go.drugbank.com/drugs/DB00590
• https://www.rxlist.com/consumer_Prazosin _cardura/drugs-condition.htm
• https://reference.medscape.com/drug/cardura-xl-Prazosin -342343