1. Dip. Software statistics- PhD ( physiology) IDRA, FICA
Dexmedetomidine
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu),
Dip. Diab., DCA,
Dip. Software statistics-
PhD ( physiology) IDRA, FICA

2. Eight times more specific for alpha 2 receptors than clonidine
Chemistry
Dexmedetomidine hydrochloride; Dexmedetomidine HCL;
4-((S)-alpha,2,3-trimethylbenzyl)imidazole monohydrochloride
Eight times more specific for alpha 2 receptors than clonidine

3. Physiology
Alpha 2 receptor agonist There are three types of alpha two( α2 a, α2 b, α2 c) receptors α2 a- sedation, analgesia , sympatholysis α2 b- spinal analgesia , peripheral vasoconstriction α2 c – modulation of cognition, sensory processing, mood changes

4. Pictures from the net for closed academic purpose only

5. How does it act ? Αlpha 2 stimulation Decreased CAMP Potassium efflux
Nerve hyper polarization
Decreased calcium entry

6. Alpha 2 is presynaptic and alpha 1 is post synaptic

7. Pharmacokinetics
Following intravenous administration, dexmedetomidine shows rapid distribution phase with a distribution half life of six minutes and a terminal elimination half life (t1/2) of approximately two hours
Oral ?? But nasal and sublingual use is proved
Nasal 1- 2 µg/kg has an onset of 20 minutes
Cytochrome p 450 glucorinidation and hydroxylation and excreted through kidneys

10. Adrenergic agonists Alpha Beta Isoprenaline Dexmed Dopamine Clonidine
Phenyleph
Dobutamine
Oxymetazoline
Isoprenaline
Noradrenaline
Terbutalin
norad
Adrenaline
Alpha
Beta
Alpha 1
Alpha 2
Beta 1
Beta 2
Beta 3
Ephedrine
Ephedrine

11. Clinical applications

12. Perioperative hemodynamics
0.25 – 1 µg/kg - Blunted Pressor response to intubation
Better intraop hemodynamics
No reflex tachycardia as inhalational agents
0.5 µg/kg blunted extubation response also
Hypotension and bradycardia are the common side effects
Used for Deliberate hypotension

13. Dexmedetomidine is an effective and safe agent for controlled hypotension mediated by its central and peripheral sympatholytic action.

14. In cardiac
Dexmedetomidine in addition to blunting the hemodynamic response to endotracheal intubation also reduces the extent of myocardial ischemia during cardiac surgery
Decrease pulmonary hypertension in MVR cases

15. Perioperative analgesia
0.8 µg/kg doses decreased morphine requirements by 60 % in major cases .
Infusion of 0.4 µg/kg/hour decreased opioids by 66% in the 24 hour period
Superior to clonidine but duration only two hours
Nausea and vomiting less Why??
opioids less !!

16. Perioperative analgesia (continued)
Analgesic effects of Dex were associated with more incidence of postoperative bradycardia
But usually – asymptomatic
Beware of combined beta blockers – increased stroke incidence
Dexmed on chronic pain or hyperalgesia – not established

17. Awake fiber optic intubation
Routine midaz or opioids
Respiratory depression in compromised airways
But dexmed – OK
Loading dose with continued infusion
Sympatholysis , analgesia, sedation --- yes
But some decreased salivary secretion effect ?? !!

18. Adjunct to GA Stress reduction equivalent to epidural in some studies
When epidural is risky ??
Decreased dosage requirement of propofol on induction and TIVA
Decreased dosage – rocuronium

19. Sedation is OK ??
Dexmedetomidine does not cause respiratory depression.
This fact can be utilized in sedating morbidly obese patient thereby avoiding respiratory depression caused by narcotics
High dose dexmedetomidine (3mcg/kg IV load over 10 minutes with an infusion of 1 mcg/kg/hour) has been used successfully for sedation of children undergoing MRI.( BRADY ?)

20. On the CNS surgery side ??
Dexmedetomidine provides stable cerebral hemodynamics
NO sudden increase in ICP during intubation, extubation, and head pin insertion.
It attenuates neurocognitive impairment (delirium and agitation) allowing immediate postoperative neurological evaluation.
Some neuroprotective effects

21. Special
awake craniotomy for the resection of tumors or epileptic foci in eloquent areas,
the implantation of deep brain stimulators for Parkinson’s disease
No interference with neuro monitoring

22. Dexmeditomedine has high lipophilicity and so it passes through placenta but it disappears very fast.
Cautious in pregnancy and lactation
Intrathecal also – risk Vs benefit

23. Loco regionals - in nerve blocks
Dexmed shortens onset
Prolongs sensory and motor blockade
Duration prolonged by more than 16 hours extra with 150 mic.gm of dexmed
Not due to CNS effects or vasoconstriction
But probably hyperpolarization is the mechanism
But IV also prolongs nerve blocks !!
Hypotension and bradycardia remains

24. Neuraxial blockade 1 µg/kg – epidural –
prolongs sensory and motor blockade
No without major side effects
Caudal additive in children – good results
3 – 10 µg single dose combining with spinal local anesthetics – similar results
IV dexmed can prolong sensory and mainly analgesic effects of spinal local anesthetics

25. Biers block 0.3 µg/kg addition Better and prolonged analgesia
Reduced local anesthetics
Possible protection from CNS and cardiac toxicity
But done and proved only in upper limbs

26. Postoperative period
Intra articular dexmedetomidine in patients undergoing arthroscopic knee surgery improves the quality and duration of postoperative analgesia
antihyperalgesic effect when administered locally after bilateral third molar surgery
Preemptive local infiltration dexmed for hernia surgery !!
Dexmed decreases the incidence of sevoflurane emergence delirium in pediatrics

27. Some potential uses ??
used successfully in the treatment of withdrawal from benzodiazepines, opioids, alcohol, and recreational drugs
Management of tetanus in ICU.
As an anti shivering agent. ?
preventing ethanol induced neuro degeneration

28. Side effects
hypotension, hypertension, bradycardia, dry mouth and nausea.
fever, rigors, cyanosis, muscle weakness.
Rarely arrhythmias, AV Block, cardiac arrest,
T-wave inversion, tachycardia, angina pectoris, pulmonary edema, bronchospasm respiratory depression, syncope, neuropathy, paresthesia, paresis, hyperkalaemia, lactic acidosis and hyperglycaemia.

29. Antagonist ??
pharmacological effects of dexmedetomidine can be reversed by α2-AR antagonist atipamezole, combination of dexmedetomidine and atipamezole can provide titratable form of sedation in the future.
Upto 30 mg / subject dose in humans – no major problems

30. Summary What is it ? Pharmacokinetics Receptors
uses - hemodynamics , cvs cns , regionals analgesia sedation, pediatrics etc
Potential uses
Antagonist

31. Thank u all