What Is Doxazosin?

Doxazosin is an 1-selective alpha blocker that inhibits the binding of norepinephrine (released from sympathetic nerve endings) to the alpha-1 receptor on the vascular smooth muscle cell membrane. The main effect of this inhibition is to relax vascular smooth muscle tone (vasodilation), which reduces peripheral vascular resistance, leading to lower blood pressure. Clinically used to treat hypertension and urinary retention associated with benign prostatic hyperplasia (BPH).

Chinese name: Doxazosin
Foreign name: Doxazosin

Indication function: Can be used for hypertension
Precautions: Adverse reactions and precautions with terazosin

Doxazosin Basic Information

Chinese name: Doxazosin

Chinese alias: 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4-[(2,3-dihydro-1,4-benzodioxane-2- ) Carbonyl] piperazine; 4-amino-2- [4- (1,4-benzodiazine-2-carbonyl) piperazin-1-yl] -6,7-dimethoxyquinazoline Nefcilin;

English name: doxazosin

English alias: Doxazosine [French]; Doxazosine; [4- (4-amino-6,7-dimethoxyquinazolin-2-yl) piperazin-1-yl]-(2,3-dihydro-1,4-benzodioxin-3- yl) methanone; 4-amino-2- [4- (1,4-benzodioxan-2-carbonyl) piperazin-1-yl] -6,7-dimethoxyquinazoline; 1- (4-amino-6,7-dimethoxy- 2-quinazolinyl) -4-[(2,3-dihydro-1,4-benzodioxin-2-yl) carbonyl] piperazine;

CAS number: 74191-85-8

Molecular formula: C ₂₄ H ₂₉ N ₅ O ₈ S

Structural formula:

Molecular weight: 547.58100

Exact mass: 547.17400

PSA: 175.02000

LogP: 2.88670

Physical and chemical properties

Density: 1.371 g / cm ³

Melting point: 289-290 ° C

Boiling point: 718ºC at 760 mmHg

Flash point: 388ºC

Security Information

Dangerous Goods Transport Code: UN 1198 3 / PG 3

WGK Germany: 2

Danger category codes: R23 / 24/25; R34; R40; R43; R36 / 37/38; R38

Safety instructions: S36 / 37; S37 / 39; S26; S36

RTECS number: LP8925000

Dangerous goods mark: T; Xi ^[1]

Doxazosin production method

Method 1: 4-amino-2-chloro-6,7-dimethoxyquinazoline and 2- (1-piperazinecarboxyl) -1,4-benzodioxane reaction Oxazine.
Method 2: Acetylation of the following fragments with methyl 1,4-benzodioxane-2-carboxylate or its acyl chloride.

Doxazosin Doxazosin Related Drug Leaflet Information Summary

Drug Name: Doxazosin

Drug description: Mesylate tablets are usually 0.5mg; 1mg; 2mg; 4mg; 8mg.

Doxazosin

Dosage: At the beginning, take orally, 0.5 mg once a day, depending on the situation, gradually increase the dose to 2 mg a day every 1 to 2 weeks, and then increase it to 4 to 8 mg a day.

Indications of doxazosin

Primary hypertension; benign prostatic hyperplasia.

Doxazosin chemical composition

The chemical name of this product is: [1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (1,4-benzodioxane-2-ylidenecarbonyl)] Piperazine mesylate.

Molecular formula: C23H25N5O5 · CH4O3S

Molecular weight: 547.59

Doxazosin adverse reactions

1 Adverse reactions with an incidence of more than 10%: dizziness, headache, burnout and discomfort.

2 Adverse reactions with incidence of 2-10%: lethargy, edema, nausea, rhinitis, dyspnea, orthostatic hypotension, palpitations, dizziness, dry mouth, visual abnormalities, neuroticism, sexual dysfunction, diarrhea, polyuria, chest pain And body pain. Orthostatic hypotension, edema, and dyspnea are often dose-dependent.

3 Adverse reactions with an incidence of about 1%: arrhythmia, hypotension, rash, itching, joint pain / arthritis, muscle weakness, myalgia, paresthesia, dyskinesia, ataxia, hypertonicity, muscle spasm, Flushing, conjunctivitis, tinnitus, depression, insomnia, constipation, indigestion, flatulence, nosebleeds, urinary incontinence, weakness and facial swelling.

4 Adverse reactions with an incidence rate of about 0.3%: tachycardia, peripheral ischemia.

Doxazosin contraindications

1 People who are allergic to quinazoline (such as prazosin, terazosin).

2 Severe hypotension occurred after taking this product.

Doxazosin drug interactions

1 Indomethacin or other non-steroidal anti-inflammatory drugs with this product can reduce blood pressure. Water and sodium retention may be caused by inhibition of renal prostaglandin synthesis and / or.

2 Cimetidine may slightly increase doxazosin plasma concentration and half-life, but its clinical significance is unknown.

3 Other antihypertensive drugs have an antihypertensive effect when used together with this product, and the dose needs to be adjusted.

4 estrogen increases blood pressure due to fluid retention when combined with this product.

5 Sympathomimetic amines combined with this product can reduce the former's pressure-boosting effect and the latter's hypotensive effect.

6 Human in vitro plasma studies have shown that doxazosin has no effect on the protein binding rates of digoxin, warfarin, phenytoin, and indomethacin.

Doxazosin pharmacological effects

Pharmacological action Doxazosin tablets are long-acting 1-receptor blockers. This product selectively acts on 1-adrenergic receptors after the node, which can expand the surrounding blood vessels, reduce the resistance of the surrounding blood vessels and reduce blood pressure, and have little effect on cardiac output. Like other 1-blockers, doxazosin has a greater effect on orthostatic blood pressure and heart rate. This product acts on the 1-adrenergic receptors of the smooth muscles of the prostate and bladder neck, relaxes the smooth muscles of the bladder neck, prostate, and prostate capsule, reduces the resistance of the urethra and the bladder, thereby reducing the symptoms of urethral obstruction caused by benign prostatic hyperplasia. This product can slightly reduce total cholesterol (2-3%), LDL-cholesterol (4%), and slightly increase HDL-cholesterol (4%). But the clinical significance of these changes is unclear. Carcinogenic, mutagenic and reproductive toxicity Rats and mice received long-term oral (24 months) maximum tolerated doses of doxazosin (40 mg / kg / day and 120 mg / kg / day), respectively, and no carcinogenic activity was found. Mutagenicity studies have not shown the effects of this product and its metabolites on the structure of chromosomes and subchromosomes. Rat studies have confirmed that oral administration of this product at 20 mg / kg / day can reduce the reproductive capacity of male rats; however, its reproductive capacity can be restored within 2 weeks after discontinuation of this product. No effect on the fertility of male rats was observed when the product was orally administered at 5 and 10 mg / kg / day. There have been no reports of the effects of this product on human male fertility. Pregnant rabbits and rats were orally administered up to 41 mg / kg and 20 mg / kg of this product daily (equivalent to 10 and 4 times the Cmax and ACU of humans taking this product at 12 mg / day), and no effect was found on the fetuses. Rabbits can reduce the survival rate of fetuses when taking this product up to 80mg / kg. Radioactivity studies have shown that this product can pass through the placenta of pregnant rats. Perinatal studies in rats have shown that daily oral administration of 40 or 50 mg / kg of this product (equivalent to 8 times the ACU of humans taking this product at 12 mg / day) can delay postnatal development of young rats. The study of lactating rats found that the maximum concentration in milk of mother rats when the single dose of [2-14C] 1mg / kg of this product was 20 times higher than that of maternal plasma.

Doxazosin pharmacokinetics

Doxazosin is well absorbed through the gastrointestinal tract, with a bioavailability of about 65%, and the peak concentration time after oral administration is 1.5 to 3.6 hours. At steady state, the peak plasma concentration and dose have a positive linear relationship. Doxazosin was taken orally at 1 mg, and the standardized peak concentration was 9.6 g / L. The single-dose antihypertensive peak action time is 5-6 hours, and the action lasts 24 hours. For hypertensive patients, the blood pressure slightly decreases within 1 hour of administration, and the antihypertensive effect is obvious after 2 hours. Effect on benign prostatic hyperplasia for 1 to 2 weeks. Protein binding rate reached 98% to 99%. Doxazosin is extensively metabolized in the liver, and although several active and inactive metabolites have been identified, their amounts are insufficient to produce an effect. The half-life is 19 to 22 hours, and it is not affected by age or mild or moderate renal impairment. It is mainly excreted by feces, 5% is the original drug, 63% to 65% are metabolites, and kidney excretion is 9%. Cannot be cleared by hemodialysis.

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Doxazosin Expert Reviews

Doxazosin selectively blocks 1 receptors. It is the first choice for mild to moderate hypertension with hyperlipidemia or prostatic hypertrophy (doxazosin can have beneficial effects on prostate hypertrophy). 2 doses. Take once before bedtime to reduce adverse reactions. For congestive heart failure, short-term use is also quite effective.