Doxazosin is a medication used to manage and treat benign prostatic hyperplasia, hypertension, ureteral stones, and PTSD-associated nightmares. It is a quinazoline derivative that acts as a competitive alpha1-antagonist. This activity describes the indications, action, and contraindications for doxazosin as a valuable agent in treating and managing benign prostatic hyperplasia, hypertension, ureteral stones, and PTSD-associated nightmares. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to healthcare providers. Objectives:
FDA approved Indications
Non-FDA Approved Indications
Doxazosin is a quinazoline derivative that acts as a competitive alpha1-antagonist at the post-synaptic receptor. In Hypertension
In Benign Prostatic Hyperplasia
Formulations
Dosing
Dose-related Adverse Effects
Common Adverse Effects
In a research study, researchers randomly assigned a total of 3,047 men were randomly assigned to groups of a placebo, doxazosin, or combination therapy with finasteride. Adverse effects of orthostatic hypotension and dizziness occurred significantly more in the groups taking doxazosin and combination treatment compared to the placebo group. Rates of adverse effects were reported to peak at year one during a mean duration of 4.5 years of treatment.[13] Contraindications for the use of doxazosin are:
Effective therapy with doxazosin for its various indications requires titration based upon response and tolerability. Open communication between patients and providers is crucial for successful treatment. Patients should receive education on the different common side effects of doxazosin, and the provider should conduct a thorough review of other medications for possible interactions, paying particular attention to other antihypertensives, nitrates, and PDE-5 inhibitors. Reports with overdosage and toxicity with the alpha-1 antagonists, including doxazosin, remain very limited in the literature. There is a report of one case of acute doxazosin overdose in 2005.[14] The study found that the patient presented to the emergency department (ED) with drowsiness, decreased blood pressure, and reflex tachycardia but did not have orthostatic hypotension or any other abnormalities. This patient was able to fully awaken with supportive therapy in 8 hours and was discharged 48 hours after admission to the ED. Although there are limited works of literature for the toxicity of doxazosin, it appears to have low acute toxicity. Doxazosin may not be a drug that providers find themselves prescribing daily. However, it has a few key contexts where it proves to be a valuable tool for health care workers in the treatment of BPH, hypertension, ureteral stones, and PTSD-associated nightmares. Doxazosin is a medication that requires titration to an effective dose and tolerance. As such, interprofessional healthcare teams need to monitor patients closely upon the initiation and titration of therapy, starting with the prescribing clinician. The extended-release formulation of doxazosin has the benefit of once-daily dosing and more stable serum concentrations. Nurses can serve as the initial point of contact for patient questions and provide initial counseling on using the drug, dosing, and what to watch for regarding possible adverse reactions. This dosing regimen reduces the incidence of orthostatic hypotension and various other adverse effects. Because doxazosin has many drug-drug interactions, it may be helpful for a pharmacist to review the different medications that a patient is on before initiating therapy. These examples of interprofessional teamwork show how such an approach can lead to improved patient outcomes with doxazosin. [Level 5] Review Questions1. Black L, Naslund MJ, Gilbert TD, Davis EA, Ollendorf DA. An examination of treatment patterns and costs of care among patients with benign prostatic hyperplasia. Am J Manag Care. 2006 Mar;12(4 Suppl):S99-S110. [PubMed: 16551208] 2.AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol. 2003 Aug;170(2 Pt 1):530-47. [PubMed: 12853821] 3.Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA, Williamson JD, Wright JT. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-e248. [PubMed: 29146535] 4.Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, Flack JM, Carter BL, Materson BJ, Ram CV, Cohen DL, Cadet JC, Jean-Charles RR, Taler S, Kountz D, Townsend RR, Chalmers J, Ramirez AJ, Bakris GL, Wang J, Schutte AE, Bisognano JD, Touyz RM, Sica D, Harrap SB. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014 Jan;16(1):14-26. [PMC free article: PMC8031779] [PubMed: 24341872] 5.Gul U, Yaycıoglu O, Kuzgunbay B, Sarıturk C, Kayra MV, Ozkardes H. Do patients on alpha-blockers for the treatment of benign prostatic hyperplasia have better results after shockwave lithotripsy of urinary stones? J Endourol. 2013 May;27(5):612-6. [PubMed: 23237326] 6.De Jong J, Wauben P, Huijbrechts I, Oolders H, Haffmans J. Doxazosin treatment for posttraumatic stress disorder. J Clin Psychopharmacol. 2010 Feb;30(1):84-5. [PubMed: 20075659] 7.Sethi R, Vasudeva S. Doxazosin for the treatment of nightmares: does it really work? A case report. Prim Care Companion CNS Disord. 2012;14(5) [PMC free article: PMC3583762] [PubMed: 23469321] 8.Rodgman C, Verrico CD, Holst M, Thompson-Lake D, Haile CN, De La Garza R, Raskind MA, Newton TF. Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial. J Clin Psychiatry. 2016 May;77(5):e561-5. [PubMed: 27249080] 9.Roepke S, Danker-Hopfe H, Repantis D, Behnia B, Bernard F, Hansen ML, Otte C. Doxazosin, an α-1-adrenergic-receptor Antagonist, for Nightmares in Patients with Posttraumatic Stress Disorder and/or Borderline Personality Disorder: a Chart Review. Pharmacopsychiatry. 2017 Jan;50(1):26-31. [PubMed: 27276365] 10.Smith C, Koola MM. Evidence for Using Doxazosin in the Treatment of Posttraumatic Stress Disorder. Psychiatr Ann. 2016;46(9):553-555. [PMC free article: PMC5033510] [PubMed: 27667865] 11.Chung M, Vashi V, Puente J, Sweeney M, Meredith P. Clinical pharmacokinetics of doxazosin in a controlled-release gastrointestinal therapeutic system (GITS) formulation. Br J Clin Pharmacol. 1999 Nov;48(5):678-87. [PMC free article: PMC2014349] [PubMed: 10594469] 12.Roehrborn CG, Schwinn DA. Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1029-35. [PubMed: 14767264] 13.Kaplan SA, Lee JY, Meehan AG, Kusek JW. Time Course of Incident Adverse Experiences Associated with Doxazosin, Finasteride and Combination Therapy in Men with Benign Prostatic Hyperplasia: The MTOPS Trial. J Urol. 2016 Jun;195(6):1825-9. [PubMed: 26678956] 14.Satar S, Sebe A, Avci A, Yesilagac H, Gokel Y. Acute intoxication with doxazosin. Hum Exp Toxicol. 2005 Jun;24(6):337-9. [PubMed: 16004202] |