Nov 01, 2014
Clonidine
The ‘wonder drug’- most misunderstood!
ConsultantDepartment of Anesthesiology
&Intensive care
Public Hospital Authority’s Rand Memorial HospitalFreeport, Grand Bahama
The Bahamas
Dr. M. M. PANDITRAO
Chemical Structure
2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride
α2 Adrenoceptor Agonist -Clonidine
Agonist to postsynaptic α2 adrenoceptors in brain, stimulation suppresses sympathetic outflow.
High dose activates peripheral presynaptic autoreceptors on adrenergic nerve endings mediating negative feedback suppression of noradrenaline release.
Clonidine reduces blood pressure.
Overdose stimulates peripheral postsynaptic α1 adrenoceptors & cause hypertension by vasoconstriction.
Abrupt or gradual withdrawal causes rebound hypertension.
Treatment is to reinstitute clonidine.
Never use Clonidine with β- adrenoceptorblockers.
Mechanism of Analgesia
Clonidine attenuates the opioid withdrawal syndrome.
“Indicating interaction with intrinsic
Opioid System”
Mechanism of Analgesia (Contd.)
Clonidine induced Analgesia is mediated by an agonist effect at:
α2
adrenoceptors or Imidazoline
receptors
resulting in: ►
Mechanism of Analgesia (Contd.)
Peripheral & central suppression of sympathetic transmitter release
Pre-synaptic inhibtion of nociceptive afferents
Post-synaptic inhibition of spinal cord neurones
Facilitating the Brain-stem pain modulating system
Pharmacokinetics
Well absorbed orally Nearly 100% bioavailableThe mean half life of the drug in plasma is about 12 hoursIt is excreted in an unchanged form by the kidneyThree or four days are required to achieve steady state concentrations Onset may be rapid (a few hours) or delayed for as long as 2 days and subsides over 2-3 days
Pharmacokinetics (Contd.)
Epidurally: Absorbed into CSF, peak within 30-60 min.
excellent correlation between Analgesia & CSF levels.
Peak blood levels within 10 min. Poor correlation between Analgesia & blood
levels Metabolism-minimal: p-hydroxyclonidine Excretion- majority unchanged: Urine
I.V/ I.M./Intrathecally: mimics epidural route
Adverse effects
Dry mouth SedationBradycardia Sexual disfunction20% of patients develop a contact dermatitis to the transdermal delivery systemWithdrawal syndrome and potentially life threatening rebound hypertension
Precautions & Warnings
Withdrawal causes rebound hypertension
Caution needed in Cerebrovascular & coronary insufficiency
Sedation is common with neuraxial route
Like other antihypertensives, in CHF pts. ‘high level monitoring’ needed
Very little amount of Clonidine removed by dialysis, so ‘high level monitoring’ needed in CRF patients
Drug Interactions
Non selective adrenergic blockers
Diuretics, Vasodilators & adrenergic blockers
NSAIDs
Therapeutic usesThe major use of clonidine is in the treatment of hypertension.
Clonidine is useful in the management of withdrawal symptoms seen in addicts after withdrawal from opiates, alcohol, and tobacco.
due to its ability to suppress sympathomimetic symptoms of withdrawal.
• Low dose Clonidine (50-100µg/dl) is used in migraine prophylaxis and chorea.
• As an analgesic and adjuvant to LAAs / GA
Therapeutic uses (Contd.)
Has been successfully used to relieve the Myo-spasms and hypertonia in spinal cord injury patients
To improve the gastroparesis and ch. Diarrhea secondary to Diabetes mellitus
To relieve “Hot Flushes” associated with menopausal hormonal disturbances both in males as well as females
Clonidine in Regional Anaesthesia
Published Reports of Pts. Receiving Clonidine for Regional Anaesthesia
Effect of route of administration on duration of analgesia from a small dose of clonidine by Intra- Muscular, Epidural,
Placebo & Spinal Routes
Cholinergic interaction in spinal α 2 -adrenergic analgesia
Descending noradrenergic pathways release norepinephrine (NE), to cause analgesia directly and to stimulate acetylcholine (ACh) release, to produce analgesia (left). This is consistent with an increase in cerebrospinal fluid (CSF) acetylcholine after epidural clonidine injection (right, above) and with neostigmine's potentiation of clonidine analgesia in humans (right, below).
Sites of hemodynamic actions of
α 2 -adrenergic agonists
α -Adrenergic agonists
produce sympatholysis and reduced BP by actions in the periphery, brainstem, and spinal cord, effects opposed by direct vasoconstriction from α 2 -adrenergic agonists in the periphery. As a result of the spinal sympatholytic site of action, epidural clonidine reduces blood pressure more when injected in the thoracic than in the cervical or lumbar space
Effect of Addition of Epidural Clonidine to Bupivacaine for
Labour Analgesia
Clonidine added to mepivacaine for brachial
plexus block
In 190 patients from 3 controlled studies receiving 40 ml 1% mepivacaine for brachial plexus block, clonidine produced dose-dependent increases in duration of anesthesia (open circles) and analgesia (solid circles). Data from each study are connected by lines.
Summary of Clinical Experience with Clonidine for Regional Anesthesia
Conclusion
α -Adrenergic agonistsParenteral PreparationUnique PharmacologyMultiple IndicationsGood safety ProfileAdequate Clinical experience
“So It is going to stay & Prosper”