Alpha-Blockers

Mechanism of Action

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

There are two types of alpha-adrenergic 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 the 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 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 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 the 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 nurses. 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 nurses to collaborate to prevent adverse effects, especially in the elderly.