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.
Side Effects and Contraindications
Side effects relate to the wide range of action of the drugs. These particularly include vomitting, hypertension and uterine contraction.
Drugs in this Group
Xylazine
Xylazine is available as a 2% solution for use in cattle, horses, cats and dogs, and a 10% solution for use in horses. A powdered form is also licensed in horses. Intramuscular administration