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.
Pharmacokinetic Considerations
There is great variation between species sensitivity to alpha-2 agonists. Cattle are ten times as sensitive to the drugs as horses.
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 above, causes excessive urination.
- Growth hormone release is triggered by alpha-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. A 10% solution for horses may be used for pre-medication prior to ketamine anaesthesia or analgesia in, for example, colic cases. A powdered form is also licensed in horses. Intramuscular and intravenous administration both have a short onset time of 5 minutes. The peak effect occurs 10 minutes after intramuscular injection, and the duration of the drug's actions is 20 mins following intravenous administration. Intravenous use is only licensed in dogs and cats.
Xylazine must not be used in the last month of pregnancy, since it causes uterine contractions. The drug is also arrhythmogenic.
Detomidine
Detomidine is available as a 10mg/ml solution in multidose vials. It is licenced for use in cattle and horses. It can be administered via an intravenous or intramuscular route. Although oral dosing is ineffective, it is readily absorbed across mucous membranes so may be adminstered sublingually. Its main indication for use is sedation in the horse for examinations, such as rectal or endoscopic, minor surgical procedures, as part of a premedication regime or before treatment, such as shoeing.
Medetomidine
Medetomidine is available as a 1mg/ml solution for use in dogs and cats.It is non irritant so therefore can be administered via an intravenous, intramuscular or subcutaneous route. Intravenous administration produces the most rapid effects, and the least amount of vomiting compared to other routes of administration. When given via an intramuscular route, maximal effects are not seen until 20 minutes after administration, although some sedation may be seen as early as 5 minutes. It is a very effective premedicant reducing the MAC of inhalation agents, and can be used in combination with ketamine in cats to induce anaethesia.
Romifidine
Romifidine is available as a 10mg/ml solution for use in horses. Its main indication for use is as a sedation agent and may be used in a premedication regime. It produces less ataxia and the head does not lower as much when compared to xylazine but the duration of action is longer.