Clonidine is a highly selective α2-agonist (α2:α1 = 200 : 1). It was introduced as a centrally acting antihypertensive, but abrupt discontinuation of therapy results in potentially dangerous rebound hypertension and it has fallen out of favour.

CNS effects

Clonidine produces sedation, anxiolysis and analgesia. It also has a MA Csparing effect, but there is a ceiling to the reduction because of the potential for activity at α1 receptors when used at higher doses.

CVS effects

The cardiovascular effects of clonidine probably involve α1 receptors and imidazoline receptors as with dexmedetomidine. Clonidine lowers the set point around which arterial pressure is regulated.

Respiratory effects

Clonidine has minor respiratory effects, causing only a small reduction in minute ventilation.

Pharmacokinetics

Clonidine is lipid soluble and rapidly absorbed after oral administration, with a peak plasma concentration occurring in 60–90min. O ral, intravenous and intramuscular routes may be used for sedation or analgesia. I n addition, epidural and intrathecal clonidine is used to augment regional anaesthesia, but perineural administration is of limited or no effect. The elimination halflife is 9–13h and is prolonged in renal failure. Fifty percent of an administered dose is excreted unchanged by the kidneys, and 50% is metabolised in the liver to inactive metabolites.

Dosage

Dosage for clonidine is as follows:

? Premedication: 150–300 μg orally given 1–2 h preoperatively.
? Critical care: 0–4 μg kg?1 hr?1 i.v. as a sedative, especially for agitation in drug-dependent individuals.