Clonidine is an alpha-2 receptor agonist that down regulates the sympathetic nervous system. By stimulating alpha-2 adrenergic receptors in the brain stem, clonidine activates inhibitory pathways in the central nervous system (CNS), which results in reduced catecholamine release and reduced sympathetic outflow from the CNS.
This effectively causes a decrease in blood pressure, heart rate, peripheral resistance, and renal vascular resistance.
It’s mechanism of action makes it a useful antihypertensive agent but also enables it to combat effects of drug withdrawal, especially nicotine and opioids (including heroin and methadone).
Both nicotine and opioid withdrawal typically involve catecholamine release with such varied symptoms as pupillary dilatation, lacrimation, rhinorrhea, piloerection, yawning, sneezing, anorexia, nausea, vomiting, and diarrhea. Clonidine has been found to be effective in counteracting these sympathetic-mediated symptoms through its CNS inhibitory mechanisms.
What to Do
For withdrawal, it should be started via the oral route. Clonidine is typically given at 0.1 mg by mouth (PO) 2 to 4 times per day. An alternate approach for rapid detoxification, using this drug in conjunction with naltrexone, is clonidine 6 mcg/kg/day PO divided into 3 doses the first day, increased to 11 mcg/kg/day PO divided into 3 doses on day two, then tapered to 0.6 mcg/kg/day PO divided into 3 doses on the third day. Increased side effects of clonidine use are likely with higher doses, and include orthostatic hypotension, sedation, dry mouth, and constipation.
Clonidine can be continued PO and gradually tapered over a 10-day period or converted to a 7-day transdermal patch, using the following conversion protocol:
- Day 1: Place transdermal clonidine. Additionally, administer 100% of oral dose.
- Day 2: Patch remains; administer 50% of oral dose.
- Day 3: Patch remains; administer 25% of oral dose.
- Day 4: Patch remains; no further oral clonidine necessary.
Abrupt discontinuation of clonidine may cause a hypertensive rebound and symptoms of sympathetic overactivity. Severe hypertension can be seen 12 to 36 hours after the last dose, especially in patients receiving higher doses. Clonidine, therefore, should be tapered gradually over several days with close monitoring for the signs and symptoms of clonidine withdrawal. It should be remembered that during clonidine withdrawal, concomitant beta blockade may worsen rebound hypertension.
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