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.