Doxazosin

Last updated

Doxazosin
Doxazosin.svg
Doxazosin ball-and-stick.png
Clinical data
Pronunciation /dɒkˈszəsɪn/
dok-SAY-zə-sin OR
/ˌdɒksəˈzsɪn/
DOK-sə-ZOH-sin
Trade names Cardura, Carduran, others
AHFS/Drugs.com Monograph
MedlinePlus a693045
License data
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 65%
Protein binding 98%
Metabolism Liver
Elimination half-life 22 hours
Identifiers
  • (RS)-2-[4-(2,3-Dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.128.642 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H25N5O5
Molar mass 451.483 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • O=C(N3CCN(c2nc1cc(OC)c(OC)cc1c(n2)N)CC3)C4Oc5c(OC4)cccc5
  • InChI=1S/C23H25N5O5/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26) Yes check.svgY
  • Key:RUZYUOTYCVRMRZ-UHFFFAOYSA-N Yes check.svgY
   (verify)

Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate), hypertension (high blood pressure), and posttraumatic stress disorder (PTSD). [1] [2] For high blood pressure, it is a less preferred option. [2] It is taken by mouth. [2]

Contents

Common side effects include dizziness, sleepiness, swelling, nausea, shortness of breath, and abdominal pain. [2] Severe side effects may include low blood pressure with standing, an irregular heart beat, and priapism. [2] [3] It is a α1-selective adrenergic blocker in the quinazoline class of compounds. [2]

Doxazosin was patented in 1977 and came into medical use in 1988. [4] It is available as a generic medication. [3] In 2021, it was the 195th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [5] [6]

A 2021 study associated doxazosin with decelerated biological aging in humans and confirmed its causal role in longevity in C. elegans. [7]

Medical uses

High blood pressure

Doxazosin is usually added to other antihypertensive therapy such as calcium channel antagonists, diuretics, beta-adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers. [8]

Doxazosin is generally considered to be safe, well tolerated and effective as an add-on (adjunctive) antihypertensive drug. [9]

Like other alpha-1 receptor antagonists, it has a role in the peri-operative management of pheochromocytoma. [10]

Benign prostatic hyperplasia

Doxazosin is considered to be effective in reducing urinary symptom scores and improving peak urinary flow in men with benign prostatic hypertrophy. [11] The bladder neck is densely packed with alpha-1 receptors.

PTSD nightmares and flashbacks

Sympatholytic drugs, including prazosin and doxazosin, are used for nightmares and flashbacks in posttraumatic stress disorder (PTSD). Doxazosin is very well tolerated for this constellation of symptoms. Given its long half-life, doxazosin lasts much longer than prazosin. While prazosin is dosed up to 4 times daily, doxazosin is generally dosed only once daily (at night). Both are alpha-1 antagonists. Other sympatholytic drugs include clonidine and guanfacine, which are alpha-2 agonists; they are not in the same exact class as doxazosin and prazosin.

History

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study stopped its arm of the trial looking at alpha blockers, because doxazosin was less effective than a simple diuretic, and because patients on doxazosin had a 25% higher rate of cardiovascular disease and twice the rate of congestive heart failure as patients on diuretics. [12] Pfizer, aware of the results before publication, launched a marketing campaign in early 2000, and sales were largely unaffected, despite the dangers highlighted by the study. [13] [14]

Related Research Articles

<span class="mw-page-title-main">Benign prostatic hyperplasia</span> Noncancerous increase in size of the prostate gland

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Avapro among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

<span class="mw-page-title-main">Telmisartan</span> Angiotensin II receptor antagonist

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine.

<span class="mw-page-title-main">Prazosin</span> Antihypertensive drug

Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a less preferred treatment of high blood pressure. Other uses may include heart failure and Raynaud syndrome. It is taken by mouth.

Alpha-1 blockers constitute a variety of drugs that block the effect of catecholamines on alpha-1-adrenergic receptors. They are mainly used to treat benign prostatic hyperplasia (BPH), hypertension and post-traumatic stress disorder. Alpha-1 adrenergic receptors are present in vascular smooth muscle, the central nervous system, and other tissues. When alpha blockers bind to these receptors in vascular smooth muscle, they cause vasodilation.

<span class="mw-page-title-main">Phenoxybenzamine</span> Alpha blocker medication

Phenoxybenzamine is a non-selective, irreversible alpha blocker.

Nocturia is defined by the International Continence Society (ICS) as "the complaint that the individual has to wake at night one or more times for voiding ". The term is derived from Latin nox – "night", and Greek [τα] ούρα – "urine". Causes are varied and can be difficult to discern. Although not every patient needs treatment, most people seek treatment for severe nocturia, waking up to void more than 2 or 3 times per night.

<span class="mw-page-title-main">Tamsulosin</span> Medication

Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a kidney stone is better when the stone is larger. Tamsulosin is taken by mouth.

<span class="mw-page-title-main">Fenoldopam</span> Antihypertensive agent, also used in hypertensive crisis

Fenoldopam mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. Fenoldopam is used as an antihypertensive agent. It was approved by the Food and Drug Administration (FDA) in September 1997.

<span class="mw-page-title-main">Silodosin</span> Chemical compound

Silodosin, sold under the brand name Urief among others, is a medication for the symptomatic treatment of benign prostatic hyperplasia. It acts as an alpha-1 adrenergic receptor antagonist.

A sympatholytic (sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with guanfacine, they have also shown to be beneficial in the treatment of ADHD.

The first-dose phenomenon is a sudden and severe fall in blood pressure that can occur when changing from a lying to a standing position the first time that an alpha blocker drug is used or when resuming the drug after many months off. This postural hypotension usually happens shortly after the first dose is absorbed into the blood and can result in syncope (fainting). Syncope occurs in approximately 1% of patients given an initial dose of 2 mg prazosin or greater. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<span class="mw-page-title-main">Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial</span>

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, also known as ALLHAT, was a randomized, double-blind, active-controlled study comparing at the same time, four different classes of antihypertensive drugs with the rate of coronary heart disease (CHD) events in ‘high-risk’ people with hypertension. Participants were initially randomised to chlorthalidone (diuretic) versus doxazosin, lisinopril (ACE-inhibitor), and amlodipine.

Adrenergic blocking agents are a class of drugs that exhibit its pharmacological action through inhibiting the action of the sympathetic nervous system in the body. The sympathetic nervous system(SNS) is an autonomic nervous system that we cannot control by will. It triggers a series of responses after the body releases chemicals named noradrenaline and epinephrine. These chemicals will act on adrenergic receptors, with subtypes Alpha-1, Alpha-2, Beta-1, Beta-2, Beta-3, which ultimately allow the body to trigger a "fight-or-flight" response to handle external stress. These responses include vessel constriction in general vessels whereas there is vasodilation in vessels that supply skeletal muscles or in coronary vessels. Additionally, the heart rate and contractile force increase when SNS is activated, which may be harmful to cardiac function as it increases metabolic demand.

Adrenergic neurone blockers, commonly known as adrenergic antagonists, are a group of drugs that inhibit the sympathetic nervous system by blocking the activity of adrenergic neurones. They prevent the action or release of catecholamines such as norepinephrine and epinephrine. They are located throughout the body, causing various physiological reactions including bronchodilation, accelerated heartbeat, and vasoconstriction. They work by inhibiting the synthesis, release, or reuptake of the neurotransmitters or by antagonising the receptors on postsynaptic neurones. Their medical uses, mechanisms of action, adverse effects, and contraindications depend on the specific types of adrenergic blockers used, including alpha 1, alpha 2, beta 1, and beta 2.

References

  1. 1 2 "Cardura- doxazosin mesylate tablet". DailyMed. Retrieved 18 June 2021.
  2. 1 2 3 4 5 6 "Doxazosin Mesylate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 17 March 2019.
  3. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 765. ISBN   9780857113382.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 455. ISBN   9783527607495.
  5. "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  6. "Doxazosin - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  7. McIntyre RL, Rahman M, Vanapalli SA, Houtkooper RH, Janssens GE (2021). "Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging". Frontiers in Aging. 2: 708680. doi: 10.3389/fragi.2021.708680 . PMC   9261299 . PMID   35822021.
  8. Wykretowicz A, Guzik P, Wysocki H (March 2008). "Doxazosin in the current treatment of hypertension". Expert Opinion on Pharmacotherapy. 9 (4): 625–633. doi:10.1517/14656566.9.4.625. PMID   18312163. S2CID   42056694.
  9. Chapman N, Chen CY, Fujita T, Hobbs FD, Kim SJ, Staessen JA, et al. (September 2010). "Time to re-appraise the role of alpha-1 adrenoceptor antagonists in the management of hypertension?". Journal of Hypertension. 28 (9): 1796–1803. doi:10.1097/HJH.0b013e32833b912c. PMID   20543713. S2CID   31819062.
  10. Mazza A, Armigliato M, Marzola MC, Schiavon L, Montemurro D, Vescovo G, et al. (April 2014). "Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features". Endocrine. 45 (3): 469–478. doi:10.1007/s12020-013-0007-y. PMID   23817839. S2CID   25504151.
  11. Yuan J, Liu Y, Yang Z, Qin X, Yang K, Mao C (March 2013). "The efficacy and safety of alpha-1 blockers for benign prostatic hyperplasia: an overview of 15 systematic reviews". Current Medical Research and Opinion. 29 (3): 279–287. doi:10.1185/03007995.2013.766594. PMID   23323875. S2CID   26341029.
  12. Piller LB, Davis BR, Cutler JA, Cushman WC, Wright JT, Williamson JD, et al. (November 2002). "Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone". Current Controlled Trials in Cardiovascular Medicine. 3 (1): 10. doi: 10.1186/1468-6708-3-10 . PMC   149403 . PMID   12459039.
  13. Goldacre, Ben (2012) Bad Pharma How drug companies mislead doctors and harm patients, Fourth Estate, ISBN   0007350740.
  14. Lenzer J (18 January 2003). "Spin doctors soft pedal data on antihypertensives". BMJ. 326 (7381): 170. doi:10.1136/bmj.326.7381.170. PMC   1128917 .