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Alpha Blockers


Alpha Blockers

Article Author:
Dana Nachawati
Article Editor:
Jayesh Patel
Updated:
8/11/2020 11:37:43 AM
For CME on this topic:
Alpha Blockers CME
PubMed Link:
Alpha Blockers

Indications

Alpha-blockers fall into three different categories.

1. Nonselective alpha-blockers (alpha-1  and alpha-2)

Nonselective alpha-blockers include phenoxybenzamine and phentolamine. Both of these medications have FDA-approval for use in patients with pheochromocytoma. 

Phenoxybenzamine is irreversible and phentolamine in reversible alpha-blockers. Both are used intraoperatively to manage hypertensive crisis during pheochromocytoma removal.[1][2]

Phentolamine sees occasional use in the treatment of cocaine-induced cardiovascular complications. In this situation, the use of β-blockers is less desirable due to the risk of unopposed α-adrenergic receptor-mediated coronary vasoconstriction and hypertension. Although it is worth mentioning that it is not a first-line agent for this condition. 

2. Selective alpha-1 blockers

Selective alpha-1 blocker ends with the suffix "-osin." These medications include alfuzosin, doxazosin, terazosin, tamsulosin, and prazosin.

These medications are FDA approved to treat benign prostatic hyperplasia (BPH). 

These medications may also be options to treat essential hypertension. However, they are not typically first-line agents for the management of hypertension.[3]

3. Selective alpha-2 blockers

Selective alpha-2 blockers include the medications yohimbine and idazoxan.

Yohimbine has been used to treat male sexual dysfunction, although the effectiveness has not yet been established and is not currently FDA approved for this use or any other uses.

Idazoxan is being used in research, but has no established clinical role has established.[4]

Mechanism of Action

Alpha-blockers produce their pharmacological effects through alteration of the sympathetic nervous system.

There are two types of alpha receptors: alpha-1 and alpha-2. Most of the alpha-1 adrenergic receptors are located on the vascular smooth muscle (in the skin, sphincters of the gastrointestinal system, kidney, and brain) and cause vasoconstriction when activated by catecholamines such as epinephrine and norepinephrine (NE). The vasoconstriction causes an increase in both systemic arterial blood pressure and peripheral resistance. Norepinephrine has a higher affinity for this receptor than epinephrine. Alpha-2 adrenergic receptors are located on peripheral nerve endings and inhibit the release of NE when activated; this provides a feedback mechanism for NE to inhibit its release.[5]

Nonselective alpha-adrenergic antagonists cause vasodilation by blocking both alpha-1 and alpha-2 receptors. The blockage of alpha-2 receptors will increase the NE release, which will reduce the force of the vasodilation induced by blockade of the alpha-1 receptors. These medications work best when there is increased sympathetic activity such as during stress or when there is an increase in circulating catecholamines, making these medications useful for patients with pheochromocytoma.[5]

Selective alpha-1 adrenergic antagonists cause vasodilation by preventing NE from activating the alpha-1 receptor, resulting in a lowering of the blood pressure, allowing alpha-1 blockers to be used for hypertension. Alpha-1 blockers also cause relaxation of smooth muscle in the prostate, which can enable the urine to flow more freely thru the urethra, making the medications useful for the management of benign prostatic hyperplasia (BPH).[3][5] 

Selective alpha-2 adrenergic antagonists inhibit negative feedback of NE, stimulating the sympathetic nervous system. However, there are limited findings on the significance of this mechanism of action in human medicine.[5]

Administration

Phenoxybenzamine is an oral medication that can be started 10 to 14 days before the excision of the pheochromocytoma. Phentolamine is used as an adjunct during the removal of pheochromocytoma and can be administered either intramuscularly or intravenously.[6]

Selective alpha-1 blockers are oral medications best taken at night to minimize orthostatic hypotension.

Yohimbine, a selective alpha-2 blocker, is administered orally and it is discontinued as a prescription drug in the USA.[7][4]

Adverse Effects

Adverse effects of nonselective alpha-blockers include hypotension, weakness, tachycardia, and tremulousness. Hypotension is due to inhibition of the alpha-1 receptors, which causes vascular smooth muscle relaxation and vasodilation. The remaining adverse effects occur due to the increased release of norepinephrine when alpha-2 receptors become simultaneously antagonized. This release results in the stimulation of beta receptors due to the spillover of norepinephrine and results in tremulousness and tachycardia.[8]

Adverse systemic effects such as tachycardia and tremulousness are less common with the selective alpha-1 blockers. Although it can cause first-dose hypotension, syncope, dizziness, and headache due to vasodilation and vascular smooth muscle relaxation. Reflex tachycardia may occur due to a sudden decrease in blood pressure. These adverse effects tend to occur more often in the elderly and increase the risk of falls. To best avoid these adverse effects, the patient should take the medication at night.[8]

Contraindications

Alpha-blockers are contraindicated in individuals with hypersensitivity to alpha-blockers or any other component of the drug formulation.

Caution is necessary when administering alpha-blockers in elderly patients or if previous cataract surgery. These medications can complicate cataract surgery by inducing sudden iris prolapse and pupil constriction during the surgery - also known as "intraoperative floppy iris syndrome."[3][9]

Nonselective alpha antagonists have additional contraindications. Phenoxybenzamine and phentolamine are contraindicated in a breastfeeding mother. Clinicians should exercise caution if the patient has marked renal impairment, cerebrovascular disease, coronary artery disease, or current respiratory infection. These medications are not suitable for long-term use.[8]

Monitoring

Due to the risk of hypotension and tachycardia with phentolamine, it is crucial to monitor blood pressure and heart rate when administered intraoperatively for removal of pheochromocytoma.[10]

No routine monitoring or tests are currently recommended for the rest of the alpha antagonists.  

Toxicity

Alpha-blockers are frequently prescribed in the elderly male population, and toxicity is common in these individuals. The most common adverse effect is hypotension. Extremely low blood pressure can cause ischemic insult to major organs and increase the fall-risk. If toxicity suspected, general measures are necessary to optimize the blood pressure.[11] If a patient is hypotensive, he should be moved to a supine position until blood pressure and heart rate are acceptable. If the patient remains hypotensive, then the patient can be managed with fluid resuscitation. If necessary, vasopressors could be administered as a last resort.[12] There is no specific antidote available. 

Enhancing Healthcare Team Outcomes

Preventing adverse effects of medications in the elderly population requires special care and communication between physicians, pharmacists, and nursing staff. Selective alpha-1 antagonists are commonly used agents in an outpatient setting for patients with benign prostatic hypertrophy. These drugs can have significant interactions with other medications that have similar adverse effects. Clinical staff must review in detail the medical and social history of the patient before prescribing and ordering an alpha-blocker.

If a patient taking an alpha-blocker resides in a nursing facility, there should be close communication with the nursing staff closely monitoring the patient due to an increased risk of orthostatic hypotension, which can lead to a fall. Fall precautions such as bed rails, a bed alarm, and a floor protection fall mat should be a consideration. The administration of alpha-blockers requires an interprofessional team that includes physicians, pharmacists, and nursing staff to collaborate to prevent adverse effects, especially in the elderly.


References

[1] Yu M,Han C,Zhou Q,Liu C,Ding Z, Clinical effects of prophylactic use of phentolamine in patients undergoing pheochromocytoma surgery. Journal of clinical anesthesia. 2018 Feb;     [PubMed PMID: 29195099]
[2] Sambhunath D,Pankaj K,Usha K, Role of phenoxybenzamine in perioperative clinical practice. Annals of cardiac anaesthesia. 2015 Oct-Dec;     [PubMed PMID: 26440247]
[3] Alpha 1 Adrenergic Receptor Antagonists 2012;     [PubMed PMID: 31644028]
[4] Cui T,Kovell RC,Brooks DC,Terlecki RP, A Urologist's Guide to Ingredients Found in Top-Selling Nutraceuticals for Men's Sexual Health. The journal of sexual medicine. 2015 Nov;     [PubMed PMID: 26531010]
[5] Nash DT, Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. Clinical cardiology. 1990 Nov;     [PubMed PMID: 1980236]
[6] Naranjo J,Dodd S,Martin YN, Perioperative Management of Pheochromocytoma. Journal of cardiothoracic and vascular anesthesia. 2017 Aug;     [PubMed PMID: 28392094]
[7] Lepor H, Alpha-blockers for the Treatment of Benign Prostatic Hyperplasia. The Urologic clinics of North America. 2016 Aug;     [PubMed PMID: 27476124]
[8] Frishman WH,Kotob F, Alpha-adrenergic blocking drugs in clinical medicine. Journal of clinical pharmacology. 1999 Jan;     [PubMed PMID: 9987696]
[9] Christou CD,Tsinopoulos I,Ziakas N,Tzamalis A, Intraoperative Floppy Iris Syndrome: Updated Perspectives. Clinical ophthalmology (Auckland, N.Z.). 2020;     [PubMed PMID: 32109982]
[10] McMillian WD,Trombley BJ,Charash WE,Christian RC, Phentolamine continuous infusion in a patient with pheochromocytoma. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2011 Jan 15;     [PubMed PMID: 21200059]
[11] Ramirez J, Severe hypotension associated with α blocker tamsulosin. BMJ (Clinical research ed.). 2013 Nov 5;     [PubMed PMID: 24192968]
[12] Arnold AC,Raj SR, Orthostatic Hypotension: A Practical Approach to Investigation and Management. The Canadian journal of cardiology. 2017 Dec;     [PubMed PMID: 28807522]