Benzodiazepines

Benzodiazepines are primarily anxiolytics, but do have sedative effects in man and sick animals. They also cause muscle relaxation and are anticonvulsants.

Mechanism of Action

GABA is an inhibitory neurotransmitter that opens post-synaptic Cl^- channel to hyperpolarise the membrane and reduce the chance of action potential conduction occuring. Benzodiazepines modulate the GABA/Cl^- channel complexes to enhance the effects of GABA. Benzodiazepines therefore have no intrinsic activity.

Side Effects and Contraindications

Benzodiazepines give mild respiratory and cardiovascular suppression. They are however synergistic with central depressants such as barbiturates, antihistamines and alcohol. When administered to healthy animals, they can often act to increase levels of excitement, due to a disinhibition phenomenon.

Drugs in this Group

Diazepam

Diazepam (Valium) gives a variable degree of sedation. It is a muscle relaxant and therefore should not be used as a sedative in horses. It is also an anticonvulsant, and is used to control status epilepticus. Diazepam also stimulates appetite.

Diazepam may be given orally or intravenously. Intravenous administration gives a rapid onset of action. The drug is dissolved in propylene glycol, which may cause thrombophlebitis, pain on injection and cardiac arrhythmias.

As there are few cardiovascular side effect, diazepam is good for use as a premedicant. It can also be used with ketamine to induce and maintain anaethesia in the horse and in compromised small animals.

Midazolam

Midazolam is similar to diazepam. It can be give i/m, i/v or orally, and is rapidly metabolised.

Benzodiazepine Antagonists

Benzodiazepine antagonists have no intrinsic efficacy, but prevent agonist interaction with receptors. Examples include flumazenil, which is used in man following benzodiazepine overdose.

Inverse Agonists

Inverse agonists act at the GABA receptor to close Cl^- channels. They promote convulsions.