Continuing Education Activity

Prazosin is a medication used to manage and treat hypertension, benign prostatic hyperplasia, PTSD-associated nightmares, and the Raynaud phenomenon. It is a quinazoline derivative that acts as a competitive alpha1-antagonist. This activity describes the indications, action, and contraindications for prazosin as a valuable agent in treating and managing various conditions for which it has indications. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to healthcare providers.

Objectives:

• Identify the mechanism of action of prazosin.
• Describe the potential adverse effects of prazosin.
• Review the appropriate monitoring for patients receiving therapy with prazosin.
• Summarize interprofessional team strategies for improving care coordination and communication to advance and improve outcomes using prazosin.

Indications

FDA Approved Indications

Prazosin is FDA approved for the treatment of hypertension alone or in combination with other antihypertensive agents. However, this medication is not a first-line agent based on current evidence-based guidelines.[1] 

Non-FDA Approved Indications/Off-label Use 

Prazosin has therapeutic use for benign prostatic hypertrophy (BPH), post-traumatic stress disorder (PTSD) associated nightmares, Raynaud phenomenon, pheochromocytoma, and scorpion envenomation. 

Prazosin was the first alpha antagonist used for BPH. The medication is traditionally used multiple times per day, and as a result, longer-acting alpha antagonists have come to market, which provides convenience.[2]

Prazosin may reduce PTSD-associated nightmares. A systematic review by Kung et al. suggests that there is a benefit as compared to placebo in reducing the frequency and duration of nightmares.[3] However, the literature review was in a population that already had PTSD. It is unclear whether or not this medication will reduce the risk of nightmares in people without PTSD.  

Prazosin has been used in primary Raynaud phenomenon with 1mg three times daily. This intervention showed benefit in some of the patients that received treatment.[4]

Pheochromocytomas cause catecholamine surges and perioperative use of an alpha antagonist can help abate the associated symptoms. Traditionally, clinicians have used phenoxybenzamine; however, comparison among phenoxybenzamine, doxazosin, and prazosin has shown varying results.[5] Prazosin may be used as an alternative to phenoxybenzamine as it is much cheaper, and it is unclear which medication is the most efficacious.

A study in India on pediatric patients, with a sample size of 36, suggests that using prazosin in combination with standard therapy lowers mortality of envenomation from a scorpion sting.[6] Treatment doses were initially 30 µg/kg/dose, followed by a repeat dose at 3 hours, then every 6 hours, and there is a hypothesis that this helped reduce the storage of catecholamines.[7]

Mechanism of Action

Prazosin is an alpha-1 adrenergic receptor antagonist. Alpha-1-receptors are present on smooth muscle, as in the blood vessel walls, the prostate, urethra, iris dilator muscle, and brain. Alpha 1 antagonists cause smooth muscle relaxation, which can, in turn, cause a decrease in blood pressure by decreasing systemic vascular resistance. This medication can also cross the blood-brain barrier.[8] This mechanism allows for cognitive effects and hence its use in PTSD and PTSD-associated nightmares. 

CYP450 enzymes hepatically metabolize this medication. The half-life is approximately 2.5 hours; however, it persists longer in chronic renal failure and congestive heart failure.[9] No renal adjustments are necessary for chronic kidney disease or patients on hemodialysis or peritoneal dialysis.  

Administration

The route for the administration of prazosin is oral. Doses of the medication include a 1 mg capsule, 2 mg capsule, and a 5 mg capsule. 

• Hypertension treatment doses (in adults)[10]: 2 to 20 mg divided into 2 to 3 times daily doses
• BPH treatment doses: 0.5 to 1 mg twice daily, up to 4 mg/day
• PTSD treatment doses [11]: Initiate at 1mg. Maintenance at 2 to 6 mg nightly. Higher doses have seen use in military personnel, up to 16 mg nightly.
• Raynaud syndrome treatment doses: 1 mg three times daily
• Scorpion envenomation treatment doses: 30 µg/kg/dose, followed by a repeat dose at 3 hours, then every 6 hours

Adverse Effects

Serious Adverse Effects

Serious adverse effects include first-dose hypotension, and therefore it is recommended to take the initial dose at night. Also, patients may develop orthostatic hypotension and syncope. In cataract surgeries, patients taking prazosin may develop intraoperative floppy iris syndrome (IFIS) due to the drug's effect on the alpha receptors on the iris dilator muscle. However, some patients develop IFIS without using alpha-adrenergic receptor antagonists prior to surgery [12].  Other serious adverse effects include priapism. 

Common side effects found in 5 to 10% of patients are dizziness, headaches, drowsiness, lack of energy, weakness, palpitations, and nausea. An extensive list of side effects can be found below with their occurrence rates. 

Serious Adverse Effects

1. First dose hypotension
2. Orthostatic hypotension
3. Intraoperative Floppy iris syndrome
4. Priapism
5. Syncope

Common Adverse Effects (5 to 10% of patients) (Koola)

1. Dizziness
2. Headache
3. Drowsiness
4. Lack of energy
5. Weakness
6. Palpitations
7. Nausea 

Less Common Adverse Effects (1 to 4%)

1. Vomiting
2. Diarrhea
3. Constipation
4. Edema
5. Orthostatic hypotension
6. Dyspnea 
7. Syncope
8. Vertigo 
9. Depression
10. Rash
11. Urinary frequency
12. Nasal congestion
13. Vertigo 
14. Nervousness

Rare Adverse Effects (<1%)

1. Abdominal pain
2. Tachycardia
3. Paresthesias
4. Hallucinations
5. Pruritus 
6. Incontinence 
7. Impotence and priapism

Contraindications

Previous anaphylaxis with prazosin is an absolute contraindication. Otherwise, there are no absolute contraindications of this medication, and there are no black box warnings. As with all medications, the clinician should avoid prescribing prazosin if there is a hypersensitivity or prior adverse effect with other medications in this class (including terazosin, tamsulosin, doxazosin). Caution should be used in patients with hypotension due to the potential adverse effect of orthostatic hypotension, especially considering the first-dose phenomenon associated with the initiation of therapy with prazosin. Caution is also advisable in the setting of cataracts as antagonism of the alpha-1 receptors on the iris dilator muscle can contribute to floppy iris syndrome. 

This medication is a Category C medication in pregnancy, suggesting insufficient data to support its use in humans. Other antihypertensive drugs with better safety profiles should be used first in pregnancy.

Monitoring

The use of prazosin in the setting of other vasodilatory medication or other antihypertensives increases the propensity for orthostatic hypotension. This medication does not require routine drug monitoring. However, if patients present with any severe side effects, including syncope, weakness, tachycardia, impotence, orthostatic hypotension, or others, as listed above, the provider should consider alternative treatment options. 

Toxicity

There is no direct toxicity with this medication. High doses and overdoses could lead to hypotension, and patients should be supported clinically with volume resuscitation if necessary or pressor support. 

The literature reports a case of an overdose of prazosin in a pediatric patient with hypotension, which was refractory to volume resuscitation, epinephrine, and norepinephrine support. This patient had concomitant ingestion with naproxen and acetaminophen. Given the hepatic metabolism of both acetaminophen and prazosin, this likely led to the prolonged clearing of the medication. The patient did respond to vasopressin.[13]

Enhancing Healthcare Team Outcomes

WHile prazosin is a well-tolerated medication and safe when used as indicated, it nonetheless requires the effort of an interprofessional team to manage and monitor care properly. This starts with the prescriber (MD, DO, NP, or PA), who should only use the drug when indicated. Nursing staff can answer patient questions and provide initial counsel on how to take the medication and how to watch for potential adverse reactions. The pharmacist can provide additional counseling on dosing and administration while also checking for drug-drug interacitons. These interprofessional measures will enhance patient outcomes while minimizing adverse events. [Level 5]

Evidence-based literature is reviewed in this article to help support the use of prazosin. This literature includes the articles noted in references. Patients should review the package insert and be cognizant of the potential side effects and report any new potential adverse effects to their healthcare provider. 

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 05;311(5):507-20. [PubMed: 24352797]

2.

Lepor H. Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [PMC free article: PMC2213889] [PubMed: 18231614]

3.

Kung S, Espinel Z, Lapid MI. Treatment of nightmares with prazosin: a systematic review. Mayo Clin Proc. 2012 Sep;87(9):890-900. [PMC free article: PMC3538493] [PubMed: 22883741]

4.

Wollersheim H, Thien T, Fennis J, van Elteren P, van 't Laar A. Double-blind, placebo-controlled study of prazosin in Raynaud's phenomenon. Clin Pharmacol Ther. 1986 Aug;40(2):219-25. [PubMed: 3731684]

5.

Bholah R, Bunchman TE. Review of Pediatric Pheochromocytoma and Paraganglioma. Front Pediatr. 2017;5:155. [PMC free article: PMC5508015] [PubMed: 28752085]

6.

Rodrigo C, Gnanathasan A. Management of scorpion envenoming: a systematic review and meta-analysis of controlled clinical trials. Syst Rev. 2017 Apr 08;6(1):74. [PMC free article: PMC5385045] [PubMed: 28390429]

7.

Gupta V. Prazosin: a pharmacological antidote for scorpion envenomation. J Trop Pediatr. 2006 Apr;52(2):150-1. [PubMed: 16537569]

8.

Gopalakrishna G, Popoola O, Campbell A, Nemetalla MA. Two Case Reports on Use of Prazosin for Drug Dreams. J Addict Med. 2016 Mar-Apr;10(2):131-3. [PubMed: 26900667]

9.

Jaillon P. Clinical pharmacokinetics of prazosin. Clin Pharmacokinet. 1980 Jul-Aug;5(4):365-76. [PubMed: 6994981]

10.

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. Hypertension. 2018 Jun;71(6):e13-e115. [PubMed: 29133356]

11.

Green B. Prazosin in the treatment of PTSD. J Psychiatr Pract. 2014 Jul;20(4):253-9. [PubMed: 25036580]

12.

Zaman F, Bach C, Junaid I, Papatsoris AG, Pati J, Masood J, Buchholz N. The floppy iris syndrome - what urologists and ophthalmologists need to know. Curr Urol. 2012 May;6(1):1-7. [PMC free article: PMC3783304] [PubMed: 24917702]

13.

Anderson C, Lynch T, Gupta R, Lim RK. Refractory Hypotension Caused by Prazosin Overdose Combined With Acetaminophen and Naproxen Toxicity: A Case Report and Review of the Literature. J Emerg Med. 2018 Dec;55(6):e141-e145. [PubMed: 30287134]

Disclosure: Ryan Basquez declares no relevant financial relationships with ineligible companies.

Disclosure: Micah Pippin declares no relevant financial relationships with ineligible companies.