Clonidine

Clonidine is a presynaptic alpha-2 adrenoceptor agonist which reduces noradrenaline release in the CNS leading to reduced sympathetic outflow. Chronic use reduces vascular responsiveness to vasoactive substances.

Uses

• hypertension, hypertensive crisis, torniquet induced hypertension
• reducing post-operative agitation associated with sevoflurane use in children
• prolonging duration of local anaesthetics for nerve blocks
• augmenting anaesthesia (MAC sparing).
• reducing post-op shivering
• reducing post-op nausea and vomiting
• sedation and analgesia in ICU
• diagnosis of phaeochromocytoma (clonidine suppression test – stat dose 300 mcg oral with plasma catecholamine levels before and 4-6h post dose looking for at least 50% fall in plasma noradrenaline level post dose.  Fall will not occur or will be attenuated with phaeo.)
• chronic pain, regional pain syndromes
• opiate and alcohol withdrawal

Dose

(dependent on intended treatment)

•           IV : 1.5 – 5 mcg/kg bolus (maximum 600 mcg) or 0.3 mcg/kg/h infusion. (Maximum dose in 24h 750 mcg).   Use smaller doses in children 0.5 – 2 mcg/kg initial bolus.    Give in 10mL N saline over 5 minutes
•           Prevention of postop shivering: 1 – 1.5 mcg/kg
•           Epidural/intrathecal : 1mcg/kg bolus (maximum 150 mcg) added to usual local anaesthetic agent or 30 mcg/h epidural infusion

 

Pharmaceutics

Clonidine is available as a parenteral preparation of 150 mcg/mL clonidine HCl, and as 100 mcg, 250 mcg and 300 mcg tablets.

 

Pharmacokinetics

•             Intravenously onset 5-10 min, titrate to get desired effect. Duration 3-7 hours. 
•             Beware of the delayed hypotension.
•           Oral bioavailability nears 100%
•           Highly lipid soluble drug, only 20% protein bound.
•           Mostly excreted unchanged in urine. Elimination half life prolonged in renal impairment but no modification of dosage necessary with single dose.

 

Pharmacodynamics

 

CVS

•           IV administration causes transient hypertension (alpha-1 antagonism) followed by a sustained period of hypotension. Reduced venous return may unmask underlying hypovolaemia leading to severe hypotension.
•           ± Slight bradycardia.
•           direct coronary artery vasoconstrictor but indirect vasodilator
•           can get profound rebound hypertension and tachycardia on sudden cessation (typically 18 – 72 h after last dose), with associated headache, flushing, sweating, insomnia, agitation, tremor and elevated plasma catecholamines therefore clonidine should be continued throughout the peri operative period (using parenteral dosing if required)
•           Elimination of postoperative shivering.
• Chronic use may cause orthostatic hypotension, dizziness and fluid retention and exacerbate vasospastic conditions           

CNS

•           reduces sympathetic outflow
•           reduces A-delta and C fibre inflow to higher centres thus providing analgesia
•           reduces cerebral blood flow thus reducing intracranial pressure and intraocular pressures, also reduces cerebral metabolic oxygen consumption
•           anxiolytic, may be anxiogenic at high doses
•           headache, fatigue

           

Side effects are common but mostly associated with chronic use:

•           drowsiness                  }
•           dry mouth                   } occur in up to 50% of people
•           fluid retention
•           impotence
•           constipation

Clonidine has a ceiling effect (at increasing doses becomes less alpha-2 specific causing alpha-1 mediated vasoconstriction). Dexmedetomidine is a purer alpha-2 agonist with a shorter elimination half life.  Clonidine’s long elimination half life can limit its usefulness. 

 

Withdrawal of clonidine should be done over at least 7 days to avoid a withdrawal syndrome.  Don’t stop a beta blocker simultaneously.

 

Contraindications:

•           Porphyria
•           Sick sinus syndrome/heart block
•           Pregnancy/breast feeding – ADEC category B3

 

Interactions:

  Vasoactive drugs. Beta blocker effect is accentuated.

  CNS depressants. Delayed awaking from anaesthesia or excessive sedation may be a problem.