Alpha blocker

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.

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. 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.

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.

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.

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). 

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.

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.

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.

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.

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."

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.

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.

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. 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. There is no
specific antidote available.