Centrally Acting Alpha-2 Agonists

Summary

Centrally acting alpha-2 agonists include the drugs methyldopa, guanfacine, and clonidine.

They activate alpha-2 receptors which results in vasodilation.

These drugs are used to treat hypertension, and methyldopa is particularly effective at lowering blood pressure during pregnancy. In addition, clonidine can be used to treat ADHD and opioid withdrawal.

Side effects include depression and bradycardia. If stopped abruptly, clonidine can cause rebound hypertension. These drugs are also known to cause drowsiness, dry mouth, and orthostatic hypotension.

When discontinuing clonidine, do not stop the dose abruptly and instead slowly taper down the dose over several days. When administering clonidine as a transdermal patch, replace the patch weekly and apply it to a hairless area of the body for accurate absorption.

Key Points

• Centrally Acting Alpha-2 Agonists
  • Drug Names
    • Clonidine (Catapres)
    • Methyldopa (Aldomet)
    • Guanfacine (Tenex)
  • Mechanism
    • Activates Alpha-2 Receptors
      • Stimulation of alpha-2 receptors causes the body to stop releasing catecholamines (epinephrine and norepinephrine)
    • Vasodilation
      • Reduces peripheral vascular resistance
  • Clinical Use
    • Hypertension
      • Used in pregnancy (methyldopa)
        • Methyldopa is first line treatment for gestational hypertension and mild preeclampsia
    • ADHD (clonidine)
      • The stimulation of alpha-2 receptors helps regulate attention and impulse control to treat attention-deficit/hyperactivity disorder
    • Opioid withdrawal (clonidine)
      • The stimulation of alpha-2 receptors inhibits the release of norepinephrine and other neurotransmitters involved in the stress response, mitigating withdrawal symptoms like anxiety, agitation, and cravings.
  • Side Effects
    • Drowsiness
      • Activation of alpha-2 receptors in the brainstem reduces norepinephrine release, leading to decreased arousal and alertness.
    • Depression
      • Reduced norepinephrine levels can contribute to mood changes, including symptoms of depression.
    • Dry Mouth
      • Alpha-2 receptors can be found in the salivary glands. Their activation causes decreased saliva production.
      • Can be relieved with chewing gum or frequent sips of water
    • Dizziness (Orthostatic Hypotension)
      • Instruct patient to change positions slowly to prevent dizziness and falls
    • Bradycardia
    • Rebound Hypertension (clonidine)
      • If abruptly discontinued
  • Administration
    • Transdermal Patch (clonidine)
      • Apply patch to dry, non-hairy area
      • Replace patch every 7 days
      • Apply to upper arms or torso
      • Rotate patch sites
    • Do not stop abruptly
      • The drug dose should be tapered down over 2-4 days.