Alpha-2 Agonists

Alpha-2 agonists have sedative, anxiolytic and analgesic effects.

Mechanism of Action

Alpha-2 agonists act on alpha-2 adrenoreceptors, and mimic the effects of the actual ligand binding. The sedative and anxiolytic effects arise from this process leading to pre-synaptic inhibition of noradrenaline release.

Actions

Alpha-2 agonists have a wide range of actions, due to the presence of alpha-2 receptors throughout the body. The actions most useful pharmacologically are sedation, anxiolysis and analgesia. The drugs also have a huge anaesthetic sparing effect, reducing MAC by 50-95%. They also give muscle relaxtion.

Other systems affected by alpha-2 agonists include:

• Cardiovascular System
  • Post synaptic alpha-2 effects and non-selective action on alpha-1 receptors cause vasoconstriction, hypertension and reflex bradycardia.
  • Pre-synaptic inhibition of noradrenaline release gives a reduced sympathetic outflow. This dexreases heart rate and offsets vasoconstriction.
• Respiratory System
  • The drugs cause mild depression of the respiratory systsem.
  • The response to hypercapnoea is reduced.
• Gastrointestinal Tract
  • Alpha-2 agonists cause extreme vomitting in dogs and cats. Xylazine is the worst culprit for this.
  • Huge reductions in gut motility occur following drug administration, as well as decreased salivation and secretion.
• Endocrine System
  • Alpha-2 agonists inhibit ADH, leading to diuresis.
  • Insulin is also inhibited, causing hyperglycaemia which leads to osmotic diuresis. This, along with the aboce, causes excessive urination.
  • Growth hormone release is triggered by alhpa-2 agonists.
• Urogenital Tract
  • Uterine contraction occurs with alpha-2 agonist administration.