Doxazosin

Absorption

Doxazosin is rapidly absorbed in the gastrointestinal tract and peak concentrations are achieved within 2-3 hours after administration. The bioavailability is about 60%-70%. The intake of food with doxazosin is not expected to cause clinically significant effects.

Toxicity

LD50 information
The oral LD50 of doxazosin in mice is >1000 mg/kg.
Overdose information
Symptoms of overdose include hypotension, changes in heart rate, and drowsiness. Administer supportive treatment in case of an overdose with doxazosin. Remove unabsorbed doxazosin from the gastrointestinal tract, correct hypotension, and closely monitor vital signs.

Description

Doxazosin mesylate is a selective alpha, blocker indicated for the treatment of hypertension, reportedly of special benefit as a first-line agent in the most hypertonic patient population. Another advantage of doxazosin is its favorable effect on blood lipids; it significantly increases the HDL/total cholesterol ratio and decreases the total cholesterol as well as triglycerides levels.

Originator

Pfizer (United Kingdom)

The Uses of Doxazosin

ACIPHEX therapeutic Erosive or Ulcerative Gastroesophageal Reflux Disease

Indications

Doxazosin is indicated to treat the symptoms of benign prostatic hypertrophy, which may include urinary frequency, urgency, and nocturia, among other symptoms. In addition, doxazosin is indicated alone or in combination with various antihypertensive agents for the management of hypertension. Off-label uses of doxazosin include the treatment of pediatric hypertension and the treatment of ureteric calculi.

Background

Doxazosin is an alpha-1 antagonist used for the treatment of benign prostatic hypertrophy (BPH) symptoms and hypertension. Other members of this drug class include Prazosin, Terazosin, Tamsulosin, and Alfuzosin. Because of its long-lasting effects, doxazosin can be administered once a day. It is marketed by Pfizer and was initially approved by the FDA in 1990.

What are the applications of Application

Doxazosin is a prazosin-related compound that is a selective α-1-adrenergic blocker

Definition

ChEBI: A member of the class of quinazolines that is quinazoline substituted by an amino group at position 4, methoxy groups at positions 6 and 7 and a piperazin-1-yl group at position 2 which in turn is substituted by a 2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl roup at position 4. An antihypertensive agent, it is used in the treatment of high blood pressure.

brand name

Cardura (Pfizer);Carduran.

General Description

Doxazosin, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazine(Cardura), is a quinazoline compound that selectively inhibitsthe α1-subtype of α-adrenergic receptors. This agentis very useful in the management of hypertension associatedwith pheochromocytoma.

Pharmacokinetics

Doxazosin decreases standing and supine blood pressure and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose. Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin. Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels.
A note on priapism risk
In rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.

Clinical Use

Alpha-adrenoceptor blocker:
Hypertension
Benign prostatic hyperplasia (BPH)

Drug interactions

Potentially hazardous interactions with other drugs
Antidepressants: enhanced hypotensive effect with MAOIs.
Avanafil, vardenafil, sildenafil and tadalafil: enhanced hypotensive effect, avoid with tadalafil, start the others at the lowest possible dose.
Beta-blockers: enhanced hypotensive effect; increased risk of first dose hypotensive effect.
Calcium-channel blockers: enhanced hypotensive effect, increased risk of first dose hypotensive effect.
Diuretics: enhanced hypotensive effect, increased risk of first dose hypotensive effect.
Moxisylyte: possibly severe postural hypotension when used in combination.

Metabolism

Doxazosin is extensively metabolised in the liver, and excreted in faeces as inactive metabolites (6-hydroxydoxazosin) and a small amount of unchanged drug

Metabolism

Hepatic metabolism of doxazosin produces inactive O-demethylated and C-hydroxylated metabolites. Metabolism occurs via O-demethylation of the quinazoline nucleus of doxazosin or via hydroxylation of its benzodioxan portion. The enzymes involved in the metabolism of doxazosin include CYP2C19, CYP2D6, CYP2C19, and CYP3A4, which is the primary metabolizing enzyme. Doxazosin itself is considered to be mainly responsible for its pharmacological action, however, some active metabolites have been identified whose pharmacokinetics have not been adequately characterized.