CLONIDINE

Uses

Antihypertensive.

Uses

Clonidine may be useful in the treatment of acute opioid withdrawal. Epidural clonidine 1–2μgkg –1 increases the duration and potency of analgesia provided by epidural opioid or local anaesthetic drugs.

Definition

ChEBI: A clonidine that is 4,5-dihydro-1H-imidazol-2-amine in which one of the amino hydrogens is replaced by a 2,6-dichlorophenyl group.

brand name

Catapres (Boehringer Ingelheim).

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.

Clinical Use

Clonidine is an α2-adrenergic agonist and is primarily used in the cardiovascular field for blood pressure reduction . The compound induces analgesia via central α2-receptor interaction and can be used orally, parenterally or epidurally for pain treatment, often in combination with opioids or local anesthetics . Epidural clonidine – opioid combinations are preferentially used for neuropathically maintained cancer pain. The compound is additionally used for migraine prophylaxis and to reduce opioid and alcohol withdrawal symptoms . Clonidine frequently induces side effects like hypotension, sedation, drowsiness, dry mouth, and constipation. The compound is well absorbed orally.

Physiological effects

Clonidine has some effects at α1-receptors (α2/ α1 > 200 : 1). Clonidine reduces the MA C of inhalational anaesthetic agents by up to 50%. I t has a synergistic analgesic effect with opioids which may be partly pharmacokinetic because the elimination half-life of opioids is also increased.

Physiological effects

CNS effects
Clonidine produces sedation, anxiolysis and analgesia. I t 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.

Metabolic pathway

Clonidine is well absorbed orally, with peak plasma concentrations after 60–90min. I t is highly lipid soluble, and approximately 50% is metabolised in the liver to inactive metabolites; the rest is excreted unchanged via the kidneys, with an elimination half-life of 9–12h.