Article: Clonidine

Clonidine
Systematic (IUPAC) name
N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
Identifiers
CAS number	4205-90-7
ATC code	C02AC01 N02CX02, S01EA04
PubChem	2803
DrugBank	APRD00174
Chemical data
Formula	C9H9Cl2N3
Mol. weight	230.093 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	20-40%
Metabolism	?
Half life	12-16 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	℞ Prescription only
Routes	oral

Clonidine is a centrally acting antihypertensive (to lower high blood pressure) agent, used mainly for this purpose in the past. It has found new uses, including treatment of some types of neuropathic pain, opioid detoxification, and, off-label, to counter the side effects of stimulant medication such as Methylphenidate. It is also increasingly becoming a more accepted alternative to fight insomnia as the drug is less addictive than most prescription sleep aids. Because of the above effects, Clonidine is increasingly used in conjunction with stimulants to treat attention-deficit hyperactivity disorder ADHD where it's given late afternoon and/or evening for sleep and because it sometimes helps moderate ADHD associated impulsive and oppositional behavior and may reduce tics [1].

Mechanism of action

Clonidine is a centrally-acting alpha-2 agonist. It selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. These receptors close a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines (epinephrine, also known as adrenaline, and norepinephrine) in the adrenal medulla. By fooling the brain into believing that catecholamine levels are higher than they really are, clonidine causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels. The result is a lowered heart rate and blood pressure, with side effects of dry mouth and fatigue. If clonidine is suddenly withdrawn the sympathetic nervous system will revert to producing high levels of epinephrine and norepinephrine, higher even than before treatment, causing rebound hypertension. Rebound hypertension can be avoided by slowly withdrawing treatment.

An analogy would be lowering the temperature of a house by holding a lit match under the thermostat connected to the furnace.

Clonidine for Opiate withdrawals

Clonidine is regularly prescribed to opiate addicts to help alleviate their withdrawals. It is mainly used to combat the dopesickness in the first couple days of withdrawals. It helps take away the sweating, hot/cold flashes, and general restlessness. The sedation effect is also useful.

Administration

Clonidine tablets and transdermal patch

Clonidine is typically available as tablets (Catapres®, Dixarit®), as a transdermal patch (Catapres-TTS®), or as an injectable form to be given epidurally, directly to the central nervous system.