Drug information of Doxazosin


Doxazosin

Drug group:

Doxazosin is a quinazoline-derivative that selectively antagonizes postsynaptic α1-adrenergic receptors. It may be used to mild to moderate hypertension and in the management of symptomatic benign prostatic hyperplasia (BPH). α1-Receptors mediate contraction and hypertrophic growth of smooth muscle cells. Antagonism of these receptors leads to smooth muscle relaxation in the peripheral vasculature and prostate gland.

Mechanism of effect

Doxazosin acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

Pharmacodynamic

Doxazosin is an alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, Doxazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors. In the human prostate, Doxazosin antagonizes phenylephrine (alpha1 agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1a adrenoceptor, which is thought to be the predominant functional type in the prostate.

Studies in normal human subjects have shown that Doxazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of Doxazosin results from a decrease in systemic vascular resistance and the parent compound Doxazosin is primarily responsible for the antihypertensive activity.

Pharmacokinetics

Absorption

Bioavailability: Immediate release, 65%; extended release, 54-59%

Onset (antihypertensive response): Peak, 4-8 hr

Onset (BPH response): Initial, 2 wk; peak, 4-6 weeks

Duration: 24 hr

Peak plasma time: 2-3 hr

Distribution

Protein bound: 99%

Vd: 1-3.4 L/kg

Metabolism

Metabolized extensively in liver

Metabolites: 6- and 7-O-demethyl metabolites, 6'- and 7'-hydroxy metabolites, other minor metabolites (activity unknown)

Elimination

Half-life: Immediate release, 22 hr; extended release, 15-19 hr

Dialyzable: HD, no

Total body clearance: 83-140 mL/min

Excretion: Feces (65%), urine (0.6-9%)

Drug indications

kidney stone , High Blood Pressure

Dosage

Adult

Hypertension

1 mg PO qDay in AM or PM; may titrate by doubling daily dose up to 16 mg qDay based on blood pressure response; usual dosage range is 1-2 mg qDay; if therapy is discontinued for several days, initiate dose at 1 mg qDay and titrate using initial dosing regimen

Extended release: Not indicated for hypertension

Benign Prostatic Hyperplasia

Immediate release: 1 mg PO qDay; may titrate by doubling daily dose at 1-2 week intervals to maximum 8 mg/day

If therapy is discontinued for several days, initiate dose at 1 mg qDay and titrate using initial dosing regimen

Extended release: 4 mg PO qDay; may titrate based on response and tolerability every 3-4 weeks to 8 mg PO qDay

If therapy is discontinued for several days, initiate dose at 1 mg qDay and titrate using initial dosing regimen

Pediatric

(Hypertension (Off-label

Immediate release: 1-4 mg PO once daily in AM or PM

Alerts

  • Use with caution in liver disease or recent cerebrovascular accident (CVA)
  • Rule out prostate cancer before initiating therapy
  • May cause first-dose syncope or sudden loss of consciousness
  • Risk of orthostatic hypotension (dose dependent)
  • Potential for hypotension, dry mouth, and urinary complications in elderly
  • Priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation) rarely reported (probably less frequently than once in every several thousand patients), with alpha-1 antagonists, including doxazosin; because condition can lead to permanent impotence if not promptly treated, patients must be advised about seriousness of condition
  • Concomitant use of other antihypertensives (additive hypotensive effects)
  • Extended-release form not indicated for hypertension
  • Concomitant administration of immediate-release form with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension
  • May increase the risk of heart failure by exacerbating underlying myocardial dysfunction by β1Receptor stimulation with increases in renin and aldosterone
  • May cause CNS depression, which may impair ability to operate heavy machinery and performing tasks that require mental alertness
  • Allergic reactions, including urticaria, rash, angioedema, pruritus, and respiratory symptoms may occur
  • Intraoperative floppy iris syndrome reported in cataract surgery patients who received alph1-blocker therapy; discontinuing alpha-blocker therapy prior to surgery does not appear to be of benefit
  • Decreases in white blood cells (WBC) and neutrophil count reported; WBC and neutrophil counts returned to normal following discontinuation of therapy

Points of recommendation

Take doxazosin exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Doxazosin lowers blood pressure and may cause dizziness or fainting, especially when you first start taking it, or when you start taking it again.

You may feel very dizzy when you first wake up. Be careful when standing or sitting up from a lying position.

Call your doctor if you have severe dizziness or feel like you might pass out.

While using doxazosin, your blood pressure or prostate may need to be checked often.

If you stop taking doxazosin for any reason, ask your doctor before you start taking it again. You may need a dose adjustment.

If you are being treated for high blood pressure, keep using this medicine even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Pregnancy level

HAVE NOT BEEN ESTABLISHED


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