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Alpha-2 Agonists
Questions
1
How do alpha-2 agonists reduce blood pressure?
Norepinephrine activates the alpha-2 adrenergic receptor in the brain, which serves as a negative feedback mechanism to suppress the sympathetic nervous system. Drugs with alpha-2 agonist activity mimic this effect centrally, resulting in suppression of peripheral norepinephrine release and subsequently lowering blood pressure.
As a result, efficacy of these drugs is reflected by the suppression of circulating norepinephrine. This effect is also used in the clonidine-suppression test to establish autonomous catecholamine secretion by pheochromocytomas, which do not suppress catecholamine secretion in response to clonidine.
2
Which medications act primarily as alpha-2 agonists?
Clonidine, guanfacine, and methyldopa are the most commonly used alpha-2 agonists for the management of hypertension ( Table 38.1 ). Guanfacine is also used in the treatment of attention deficit/hyperactivity disorder. In addition, several medications used for other indications act primarily at the alpha-2 receptor including dexmedetomidine, which is commonly used for sedation in intensive care units ( Table 38.2 ). Lofexidine is approved for treatment of opioid withdrawal.
Table 38.1
Dosing of Commonly Used Alpha-2 Agonists
| Dosage Adjustment for Impaired: | ||||
|---|---|---|---|---|
| MEDICATION | TYPICAL DOSE RANGE | KIDNEY FUNCTION | LIVER FUNCTION | CONSIDERATIONS |
| Clonidine | 0.1–0.3 mg three times daily | Reduce dose and/or frequency | None | Half-life ∼12 hours Prolonged half-life in renal failure |
| Guanfacine | 1–4 mg once daily | None | Use with caution CYP3A4 substrate |
Half-life ∼17 hours |
| Methyldopa | 250–1000 mg two to three times daily | Reduce dose and/or frequency | None | Rare autoimmune reactions (+ANA, hemolytic anemia) and abnormal liver tests Active metabolites are renally cleared |
| Moxonidine | 0.2–0.6 mg once daily | Reduce dose and/or frequency | None | Available outside the United States Contraindicated in heart failure Prolonged half-life in renal failure |
| Tizanidine | 4–32 mg every 4–6 hours | Reduce dose and/or frequency | Contraindicated | Markedly increased during CYP1A2 inhibitors |
ANA, Antinuclear antibody.
Table 38.2
Medications with Alpha-2 Agonist Effects
| MEDICATION | NOTES |
|---|---|
| Apraclonidine eye drops | For glaucoma |
| Brimonidine eye drops | For glaucoma |
| Clonidine | Most commonly used for hypertension |
| Dexmedetomidine | Used primarily for sedation |
| Guanfacine | Approved for attention deficit/hyperactivity disorder; long half-life |
| Guanabenz | |
| Lofexidine | Approved for opioid withdrawal |
| Methyldopa | Historically used in pregnancy |
| Moxonidine | Available outside of the United States An imidazoline receptor antagonist |
| Tizanidine | Used as nonopioid pain relief |
| Xyalazine | Veterinary tranquilizer; reported contaminant in street drugs (fentanyl) |
3
When prescribing an alpha-2 agonist, what are the usual doses?
-
See Table 38.2 for usual doses of the most commonly used alpha-2 agonists.
-
Note that, in most cases, the minimal dosing period is 12 hours.
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