Indications
The indication for the use of an alpha-receptor modifying medication depends on which receptor is the target: the alpha-1 receptor or the alpha-2 receptor. Alpha-1 receptors bind catecholamines including, both epinephrine and norepinephrine. In instances in which there is hypoperfusion secondary to decreased cardiac output or decreased systemic vasculature resistance, alpha-1 receptors become stimulated. It is worth noting that these compounds are not purely selective for the alpha receptor, and often engage beta-adrenergic receptors as well. The use of alpha-1 agonists is common in all types of shock, cardiopulmonary resuscitation, and heart failure decompensation.[1] Alpha-1 agonists, such as phenylephrine, are also used to treat upper airway congestion as stimulating the receptor leads to a decreased mucus secretion.[2] Alpha-antagonists, colloquially known as alpha-blockers, work in the peripheral vasculature and inhibit the uptake of catecholamines in smooth muscle cells resulting in vasodilation and blood pressure lowering. Alpha-antagonists, including doxazosin, prazosin, and phentolamine - are primarily used in the treatment of hypertension and urinary retention.[3]
Alpha-blockers have significant use in the setting of pre-operative pheochromocytoma care.[4] Alpha-blockers are also used off-label for the treatment of post-traumatic stress disorder (PTSD).[5] Alpha-2 stimulation reduces the sympathetic outflow from the vasomotor center centrally and increases vagal tone. Peripheral presynaptic alpha-2 receptors may also reduce sympathetic tone. Alpha-2 agonists, including clonidine and guanfacine - are used as anti-hypertensives, as well.[6] Both clonidine and guanfacine are used for behavior modification in children with attention deficit disorder, as well as in adults with PTSD as well.[7][8]
Alpha-1 agonists
FDA approved indications
Oral agents
- Midodrine
- Treatment of symptomatic orthostatic hypotension
Topical agents
- Naphazoline/naphazoline-pheniramine
- Topical ocular vasoconstriction
- Use for the relief of redness in the eye/itching (pheniramine)
- Phenylephrine
- Dilate pupils (ophthalmic)
- Temporary relief of nasal congestion due to the common cold or allergic rhinitis (nasal)
- Used in the treatment of hemorrhoids (rectal/topical)
- Xylometazoline
- Temporary relief of nasal and nasopharyngeal mucosal congestion
Intravenous
- Phenylephrine
- Hypotension/shock/cardiogenic shock
- Hypotension during anesthesia: vasoconstrictor in regional analgesia
Off-label uses
Oral agents
- Midodrine
- Refractory ascites[9]
- Prevention of dialysis-induced hypotension
- Hepatorenal syndrome
- Vasovagal syndrome
Topical agents
- Phenylephrine
- Topical vasoconstriction in nasal procedures
Intravenous
- Phenylephrine
- Hypotension in patients with obstructive hypertrophic cardiomyopathy
- Priapism
Alpha-1 blockers
FDA approved indications
Oral agents
- Treatment for signs and symptoms of benign prostatic hyperplasia (BPH)[10]
- Alfuzosin
- Tamsulosin
- Doxazosin
- Terazosin
- Silodosin
- Management of hypertension; alpha-blockers not recommended as the first-line agents[11]
- Prazosin
- Doxazosin
- Terazosin
Intravenous agents
- Phentolamine
- Pheochromocytoma: Diagnosis of this condition via the phentolamine blocking test
- Extravasation management: prevention of dermal necrosis/sloughing after extravasation of norepinephrine
- Local anesthesia reversal: reversal of soft tissue anesthesia and the associated functional deficits resulting from intraoral submucosal injections of local anesthetics
- Phenoxybenzamine
- Pheochromocytoma: Treatment of sweating and hypertension associated with the condition
Off-label Uses
Specific agents
- Tamsulosin:
- Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in males
- Lower urinary tract symptoms (LUTS) in males
- Ureteral calculi expulsion
- Ureteral stent-related urinary symptoms, treatment
- Prazosin
- Post-traumatic stress disorder PTSD related nightmares and sleep disruptions[12]
- Raynaud phenomenon
- Phentolamine
- Hypertensive crisis
- Extravasation of sympathomimetic vasopressors
- Phenoxybenzamine
- Hypertensive crisis caused by sympathomimetic amines
- Micturition problems associated with neurogenic bladder
- Functional outlet obstruction and partial prostate obstruction
Other Uses
- Ureteral calculi (distal)[13]
- Alfuzosin
- Doxazosin
- Terazosin
- Silodosin
Alpha-2 agonists
FDA approved indications
Oral
- Clonidine
- Treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy (extended-release tablet)[14]
- Management of hypertension, but not recommended as first-line treatment, should be avoided in heart failure patients with a reduced ejection fraction of ischemic origin[11][15]
- Guanfacine
- Methyldopa
- Management of hypertension, not recommended first line, particular use in pregnancy; may cause positive Coombs test[11]
- Lofexidine
- Mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults[16]
- Tizanidine
- Management of spasticity; reserve treatment with tizanidine for daily activities and times when relief of spasticity is most improtant[17]
Topical
- Brimonidine
- Topical treatment of persistent (non-transient) erythema of rosacea in adults
Intravenous
- Clonidine
- Continuous epidural administration as adjunctive therapy with opioids for the treatment of severe cancer pain in patients tolerant to or unresponsive to opioids alone; more effective for neuropathic pain and less effective (or possibly ineffective) for somatic or visceral pain[18] (epidural)
- Dexmedetomidine
- Intensive care unit sedation: Sedation of initially intubated and mechanically ventilated patients during treatment in intensive care settings
- Procedural sedation: Procedural sedation before and/or during awake fiberoptic intubation; sedation before and/or during surgical or other procedures of non-intubated patients
Off- label uses
- Clonidine
- Clozapine-induced sialorrhea
- Diagnosis of pheochromocytoma
- Growth hormone stimulation test
- Opioid withdrawal
- Tourette syndrome
- Vasomotor symptoms associated with menopause
- Dexmedetomidine
- Sedation during awake craniotomy
- Treatment of shivering