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Clonidine:The Wonder Drug- Most Misunderstood

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Prof. Panditrao explains the whole new spectrum of pharmacological actions/ indications/ contra indications/ of Clonidine when used parenterally.

Publicada em: Saúde e medicina
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Clonidine:The Wonder Drug- Most Misunderstood

  1. 1. ClonidineThe ‘wonder drug’- most misunderstood!
  2. 2. Dr. M. M. PANDITRAO Consultant Department of Anesthesiology & Intensive carePublic Hospital Authority’s Rand Memorial Hospital Freeport, Grand Bahama The Bahamas
  3. 3. Chemical Structure2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride
  4. 4. α2 Adrenoceptor Agonist - ClonidineAgonist to postsynaptic α2 adrenoceptorsin brain, stimulation suppressessympathetic outflow.High dose activates peripheralpresynaptic autoreceptors on adrenergicnerve endings mediating negativefeedback suppression of noradrenalinerelease.Clonidine reduces blood pressure.
  5. 5. Overdose stimulates peripheralpostsynaptic α1 adrenoceptors &cause hypertension byvasoconstriction.Abrupt or gradual withdrawalcauses rebound hypertension.
  6. 6. Treatment is to reinstituteclonidine.Never use Clonidine with β- adrenoceptorblockers.
  7. 7. Mechanism of Analgesia Clonidine attenuates the opioid withdrawal syndrome.“Indicating interaction with intrinsic Opioid System”
  8. 8. Mechanism of Analgesia (Contd.)Clonidine induced  α2 adrenoceptorsAnalgesia is ormediated by an  Imidazolineagonist effect at: receptors resulting in:
  9. 9. 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
  10. 10. PharmacokineticsWell absorbed orallyNearly 100% bioavailableThe mean half life of the drug in plasma is about12 hoursIt is excreted in an unchanged form by thekidneyThree or four days are required to achievesteady state concentrationsOnset may be rapid (a few hours) or delayed foras long as 2 days and subsides over 2-3 days
  11. 11. 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
  12. 12. Adverse effectsDry mouthSedationBradycardiaSexual disfunction20% of patients develop a contactdermatitis to the transdermal deliverysystemWithdrawal syndrome and potentially lifethreatening rebound hypertension
  13. 13. Precautions & WarningsWithdrawal causes rebound hypertensionCaution needed in Cerebrovascular & coronaryinsufficiencySedation is common with neuraxial routeLike other antihypertensives, in CHF pts. „high levelmonitoring‟ neededVery little amount of Clonidine removed by dialysis,so „high level monitoring‟ needed in CRF patients
  14. 14. Drug InteractionsNon selective adrenergic blockersDiuretics, Vasodilators & adrenergicblockersNSAIDs
  15. 15. Therapeutic uses The 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
  16. 16. Therapeutic uses (Contd.)Has been successfully used to relieve the Myo-spasms and hypertonia in spinal cord injurypatientsTo improve the gastroparesis and ch. Diarrheasecondary to Diabetes mellitusTo relieve “Hot Flushes” associated withmenopausal hormonal disturbances both inmales as well as females
  17. 17. Clonidine in Regional AnaesthesiaPublished Reports of Pts. Receiving Clonidine for Regional Anaesthesia
  18. 18. Effect of route of administration on duration of analgesia from a small dose of clonidine by Intra- Muscular, Epidural, Placebo & Spinal Routes
  19. 19. Cholinergic interaction in spinal α 2 - adrenergic analgesiaDescending noradrenergic pathways release norepinephrine (NE), to causeanalgesia directly and to stimulate acetylcholine (ACh) release, to produceanalgesia (left). This is consistent with an increase in cerebrospinal fluid(CSF) acetylcholine after epidural clonidine injection (right, above) and withneostigmines potentiation of clonidine analgesia in humans (right, below).
  20. 20. 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
  21. 21. Effect of Addition of Epidural Clonidine to Bupivacaine for Labour Analgesia
  22. 22. 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.
  23. 23. Summary of Clinical Experience with Clonidine for Regional Anesthesia
  24. 24. Conclusionα -Adrenergic agonistsParenteral PreparationUnique PharmacologyMultiple IndicationsGood safety ProfileAdequate Clinical experience“So It is going to stay & Prosper”

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