Chemistry:Doxazosin

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

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 selective α1-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 2023, it was the 180th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[5][6]

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.[7]

Doxazosin is generally considered to be safe, well tolerated and effective as an add-on (adjunctive) antihypertensive drug.[8]

Like other alpha-1 receptor antagonists, it has a role in the peri-operative management of pheochromocytoma.[9]

Benign prostatic hyperplasia

Doxazosin is considered to be effective in reducing urinary symptom scores and improving peak urinary flow in men with benign prostatic hyperplasia.[10] 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.[citation needed]

Pharmacology

Doxazosin is an alpha-1 blocker, or an α1-adrenergic receptor antagonist.[11]

It has also been identified as a potent vesicular monoamine transporter 2 (VMAT2) inhibitor (IC50 = 8 nM).[12]

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.[13] 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.[14][15] The decision to stop the trial was controversial because the higher rate of heart failure (HF) in the doxazosin group could have been caused by misdiagnosis due to fluid retention from the medication, or because patients with existing HF stopped their diuretic treatment to switch to doxazosin. However, in the later ASCOT trial, where doxazosin was used as a third-line treatment, there was no increase in HF risk.[16]

Society and culture

Brand names

In the US, Cardura is marketed by Viatris after Upjohn was spun off from Pfizer.[17][18][19]

Research

A 2021 study associated doxazosin with decelerated biological aging in humans and confirmed its causal role in longevity in C. elegans.[20]

See also

References

  1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Cardura FDA label
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Doxazosin Mesylate Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/doxazosin-mesylate.html. 
  3. ↑ 3.0 3.1 British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 765. ISBN 978-0-85711-338-2. 
  4. ↑ Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 455. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA455. 
  5. ↑ "Top 300 of 2023". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  6. ↑ "Doxazosin Drug Usage Statistics, United States, 2013 - 2023". https://clincalc.com/DrugStats/Drugs/Doxazosin. 
  7. ↑ "Doxazosin in the current treatment of hypertension". Expert Opinion on Pharmacotherapy 9 (4): 625–633. March 2008. doi:10.1517/14656566.9.4.625. PMID 18312163. 
  8. ↑ "Time to re-appraise the role of alpha-1 adrenoceptor antagonists in the management of hypertension?". Journal of Hypertension 28 (9): 1796–1803. September 2010. doi:10.1097/HJH.0b013e32833b912c. PMID 20543713. https://lirias.kuleuven.be/handle/123456789/269628. 
  9. ↑ "Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features". Endocrine 45 (3): 469–478. April 2014. doi:10.1007/s12020-013-0007-y. PMID 23817839. 
  10. ↑ "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. March 2013. doi:10.1185/03007995.2013.766594. PMID 23323875. 
  11. ↑ "Pharmacologic basis for the use of doxazosin in the treatment of essential hypertension". Am J Med 87 (2A): 36S–44S. August 1989. doi:10.1016/0002-9343(89)90112-5. PMID 2569823. 
  12. ↑ "Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs". ACS Pharmacology & Translational Science. 22 December 2025. doi:10.1021/acsptsci.5c00538. ISSN 2575-9108. 
  13. ↑ "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. November 2002. doi:10.1186/1468-6708-3-10. PMID 12459039. 
  14. ↑ Goldacre, Ben (2012) Bad Pharma How drug companies mislead doctors and harm patients, Fourth Estate, ISBN 0007350740.
  15. ↑ "Spin doctors soft pedal data on antihypertensives". BMJ 326 (7381): 170. 18 January 2003. doi:10.1136/bmj.326.7381.170. 
  16. ↑ "2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)" (in en-US). Journal of Hypertension 41 (12): 1874–2071. December 2023. doi:10.1097/HJH.0000000000003480. PMID 37345492. 
  17. ↑ "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. https://www.businesswire.com/news/home/20201116005378/en/. 
  18. ↑ "Cardura". https://www.pfizer.com/products/product-detail/cardura. 
  19. ↑ "Brands". 16 November 2020. https://www.viatris.com/en/products/brands. 
  20. ↑ "Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging". Frontiers in Aging 2. 2021. doi:10.3389/fragi.2021.708680. PMID 35822021. 

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