1. MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics,
Recent advances - MGMC
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab. DCA,
Dip. Software statistics,
PhD(physiology)

2. Remifentanil

3. Remifentanil is a selective µ opioid agonist with an analgesic potency similar to that of fentanyl
Remifentanil is structurally unique because of its ester linkage, which renders it susceptible to hydrolysis to inactive metabolites by nonspecific plasma and tissue esterases

5. Its action culminated by metabolism and not redistribution
So no accumulation and re entry to act again
The pharmacokinetics are unchanged in renal or hepatic failure
No big individual changes

6. Analgesia – 1- 2 µg/kg ( 30 -60 seconds)bolus
Followed by 0.1 µg/kg/minute
Start acting in one minute and finish in ten minutes
Reduction of MAC by 60 %
Pediatrics – same doses but in old age 50 % reduction start
20 µg/kg – anesthetic dose

7. For postoperative analgesia, remifentanil should be initially administered by continuous infusion at a rate of 0.1 µg/kg/min.
The infusion rate may be adjusted every 5 minutes in µg/kg/min increments to balance the patient’s level of analgesia and respiratory rate

8. suppression of the transient sympathetic nervous system response to direct laryngoscopy and tracheal intubation.
safely in coronary artery bypass graft (CABG) and neurosurgery with good results.
Long duration surgeries – ideal

9. Context sensitive half life

10. MAC
As a part of sedation technique, remifentanil, in the dosages of 0.05 to 0.10 µg/kg/min in combination with midazolam, 2 mg IV, provides effective sedation and analgesia during monitored anaesthesia care
Obstetric use – contradictory – but now a lot of articles on remifentanyl infusion for labour analgesia

11. Remifentanyl should not be mixed with blood – esterases
Remifentanyl contains glycine – hence epidural and spinal use – no
Only by infusions

12. Summary Synthetic Opioid Ester moiety – esterases
1 µg/kg – infusion µg/kg/minute
1 minute – 10 minutes
Analgesia, Symp. Suppresion , MAC reduction, MAC and post operative analgesia.labour
No with blood
Glycine – no to neuraxial use
Context sensitive half life

13. Remimazolam

14. Midazolam with characters of remifentanyl
Midazolam is the parent compound of remimazolam.
As the name indicates, this new drug is midazolam incorporating pharmacokinetic properties of remifentanil.
Midazolam with characters of remifentanyl

15. Nonspecific esterases

16. remimazolam acts on GABA receptor, specifically GABA-alpha.
Other drugs acting on GABA receptors are propofol (GABA-beta), etomidate (GABA-alpha), and thiopentone (GABA-alpha), all commonly used anesthetics.
GABA is the main inhibitory neurotransmitter in the central nervous system. 

17. dose-independent ester hydrolysis
organ-independent elimination
Onset time of 1- 3 minutes
Context sensitive half life – 7 minutes
0.075 mg / kg

18. Clinical uses Single dose for premedication
Bolus followed by supplemental doses for procedural sedation.
Intravenous anesthetic along with an opioid (as part of total intravenous anesthesia)
Intensive care unit (ICU) sedation
Bretazanil and imidazanil are newer benzodiazepine agonists with less tolerance

19. Flumazenil

20. Flumazenil flumazenil is a specific benzodiazepine receptor antagonist
primarily available by injection only,
It reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine binding site on the GABA A receptor.

21. Uses Benzodiazepine overdose Zolpidem overdose Hepatic encephalopathy
Radiolabeled with the radioactive isotope carbon-11 flumazenil may be used as a radio ligand in neuroimaging -- with positron emission tomography to visualize the distribution of GABA A receptors in the human brain.

22. Pharmacokinetics
The onset of action is rapid and usually effects are seen within one to two minutes. ( 1 mg dose)
The peak effect is seen at six to ten minutes. The recommended dose for adults is 200 μg every 1–2 minutes until the effect is seen, to a maximum of 3 mg per hour.
It is available as a clear, colourless solution for intravenous injection, containing 500 μg in 5ml

23. Dependence also
the gold standard for treatment of high-dose benzodiazepine dependency is 8–10 days of low dose, slow infusion of flumazenil

24. It rapidly reverses the unconsciousness, respiratory depression, sedation, amnesia and psychomotor dysfunction produced by the benzodiazepines according to the dose.
It has no effect on EEG, cerebral metabolism and has no anticonvulsant properties
No effect on TCADs or opioids or barbiturates
Midaz > diaz > lorazepam

25. Pearls Many benzodiazepines have longer half-lives than flumazenil.
repeat doses of flumazenil may be required to prevent recurrent symptoms of overdosage.
hepatically metabolised to inactive compounds which are excreted in the urine
Subjects who are physically dependent on benzodiazepines may suffer benzodiazepine withdrawal symptoms, including seizure,

26. Pharmacokinetics Initial distribution half-life is 4 to 11 minutes
the terminal half-life is 40 to 80 minutes.
half-life to 1.3 hours in patients with moderate hepatic impairment
2.4 hours in severely impaired patients.
Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).

27. Summary Benzodiazepine receptor antagonist Uses Not useful in ??
Dependence
Dose
Side effects
Liver ?
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