Doxazosin
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| Pronunciation | /dɒkˈseɪzəsɪn/ dok-SAY-zə-sin OR /ˌdɒksəˈzoʊsɪn/ DOK-sə-ZOH-sin |
| Trade names | Cardura, Carduran, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a693045 |
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| Routes of administration | By mouth |
| Drug class | α1 blocker |
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| Pharmacokinetic data | |
| Bioavailability | 65% |
| Protein binding | 98% |
| Metabolism | Liver |
| Elimination half-life | 22 hours |
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| ECHA InfoCard | 100.128.642 |
| Chemical and physical data | |
| Formula | C23H25N5O5 |
| Molar mass | 451.483 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Doxazosin, sold under 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 2022, it was the 180th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[5][6]
Medical uses
[edit]High blood pressure
[edit]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
[edit]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
[edit]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]
History
[edit]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.[11] 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.[12][13] 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.[14]
Society and culture
[edit]Brand names
[edit]In the US, Cardura is marketed by Viatris after Upjohn was spun off from Pfizer.[15][16][17]
Research
[edit]A 2021 study associated doxazosin with decelerated biological aging in humans and confirmed its causal role in longevity in C. elegans.[18]
References
[edit]- ^ a b "Cardura- doxazosin mesylate tablet". DailyMed. Retrieved 18 June 2021.
- ^ a b c d e f "Doxazosin Mesylate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 17 March 2019.
- ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 765. ISBN 9780857113382.
- ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 455. ISBN 9783527607495.
- ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
- ^ "Doxazosin Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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:10.1185/03007995.2013.766863. PMID 23323875. S2CID 26341029.
- ^ 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.
- ^ Goldacre, Ben (2012) Bad Pharma How drug companies mislead doctors and harm patients, Fourth Estate, ISBN 0007350740.
- ^ 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.
- ^ Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. (December 2023). "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)". Journal of Hypertension. 41 (12): 1874–2071. doi:10.1097/HJH.0000000000003480. hdl:11379/603005. PMID 37345492.
- ^ "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. Retrieved 17 June 2024 – via Business Wire.
- ^ "Cardura". Pfizer. Retrieved 17 June 2024.
- ^ "Brands". Viatris. 16 November 2020. Retrieved 17 June 2024.
- ^ 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.
