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Prazosin


Prazosin

Article Author:
Ryan Basquez
Article Editor:
Micah Pippin
Updated:
6/25/2020 10:58:09 AM
For CME on this topic:
Prazosin CME
PubMed Link:
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 in 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 provide 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 the use of 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 to reduce the catecholamine store.[7]

Mechanism of Action

Prazosin is an alpha-1 adrenergic receptor antagonist. Alpha-1-receptors are present on smooth muscle, as in the walls of the blood vessel, 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

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), which is due to alpha receptors on the iris dilator muscle. However, some patients develop IFIS without the use of 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 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 that there is 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. 

There has been a case report 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

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. 


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 Jr,Svetkey LP,Taler SJ,Townsend RR,Wright JT Jr,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 5;     [PubMed PMID: 24352797]
[2] Lepor H, Alpha blockers for the treatment of benign prostatic hyperplasia. Reviews in urology. 2007 Fall;     [PubMed PMID: 18231614]
[3] Kung S,Espinel Z,Lapid MI, Treatment of nightmares with prazosin: a systematic review. Mayo Clinic proceedings. 2012 Sep;     [PubMed PMID: 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. Clinical pharmacology and therapeutics. 1986 Aug;     [PubMed PMID: 3731684]
[5] Bholah R,Bunchman TE, Review of Pediatric Pheochromocytoma and Paraganglioma. Frontiers in pediatrics. 2017;     [PubMed PMID: 28752085]
[6] Rodrigo C,Gnanathasan A, Management of scorpion envenoming: a systematic review and meta-analysis of controlled clinical trials. Systematic reviews. 2017 Apr 8;     [PubMed PMID: 28390429]
[7] Gupta V, Prazosin: a pharmacological antidote for scorpion envenomation. Journal of tropical pediatrics. 2006 Apr;     [PubMed PMID: 16537569]
[8] Gopalakrishna G,Popoola O,Campbell A,Nemetalla MA, Two Case Reports on Use of Prazosin for Drug Dreams. Journal of addiction medicine. 2016 Mar-Apr;     [PubMed PMID: 26900667]
[9] Jaillon P, Clinical pharmacokinetics of prazosin. Clinical pharmacokinetics. 1980 Jul-Aug;     [PubMed PMID: 6994981]
[10] Whelton PK,Carey RM,Aronow WS,Casey DE Jr,Collins KJ,Dennison Himmelfarb C,DePalma SM,Gidding S,Jamerson KA,Jones DW,MacLaughlin EJ,Muntner P,Ovbiagele B,Smith SC Jr,Spencer CC,Stafford RS,Taler SJ,Thomas RJ,Williams KA Sr,Williamson JD,Wright JT Jr, 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 (Dallas, Tex. : 1979). 2018 Jun;     [PubMed PMID: 29133356]
[11] Green B, Prazosin in the treatment of PTSD. Journal of psychiatric practice. 2014 Jul;     [PubMed PMID: 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. Current urology. 2012 May;     [PubMed PMID: 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. The Journal of emergency medicine. 2018 Dec;     [PubMed PMID: 30287134]