New drugs introduced in anesthesia

practice,
Sugammadex, Cis-atracurium,
Remifentanyl and Palonosetron.
DR. TEJESWI SAI
 Sugammadex
Cyclodextrin in structure.
Modified γ-cyclodextrin with a
lipophilic core and a hydrophilic
periphery.
Reversal of neuromuscular blockade (NMB) produced by the
aminosteroid non-depolarizing muscle relaxants - Rocuronium
and Vecuronium.
Sugammadex forms a complex with Rocuronium or Vecuronium
by encapsulating them in the central compartment, removing
them from the neuromuscular junction, and thus restoring
muscle function.
Sugammadex encapsulates with a 1:1 ratio.
The complex is eliminated through renal pathway.
 Co-administration of an antimuscarinic agent
(glycopyrrolate or atropine) is not needed. Sugammadex might
therefore be expected to have fewer adverse effects than the
traditional reversal agents.
Sugammadex has a lower affinity for Vecuronium than for Rocuronium.
Yet reversal of vecuronium is still effective, because fewer vecuronium
molecules are present, since Vecuronium is approximately seven times
more potent than rocuronium.
More effective than placebo (no medication) or neostigmine in
reversing muscle relaxation caused by neuromuscular blockade during
surgery and is relatively safe.
Cis atracurium
Combining the name "atracurium" with "cis" because the molecule is
one of the three cis-cis isomers comprising the ten isomers of the
parent, atracurium.
Benzylisoquinolium structure.
 The primary clinical disadvantage of atracurium was likely to be its
propensity to elicit histamine release.
The isomer that might possibly retain the desirable properties without
the histamine release.
Binds to cholinergic receptors on motor end plate.
Cis-atracurium spontaneously degrades at physiological pH
via Hoffmanns elimination to yield laudanosine and the quaternary
monoacrylate.
Hofmann elimination is a temperature- and plasma pH-dependent
process.
Metabolite of Cis-atracurium via Hoffmann elimination is laudanosine.
Metabolism
80% to laudanosine
20% is metabolized hepatically or excreted renally.
10-15% of the dose is excreted unchanged in the urine.
No dose adjustments required in renal or liver failure.
The pharmacokinetics of cis atracurium following infusion is
same as following a bolus injection.
Elimination half life: 22 - 29 minutes.
Dose: 0.15 mg/kg (3* ED95 ). Intubating conditions 2 minutes
after administration.
Infusion dose- 1-2 μg/kg/min.
Laudanosine (metabolite)
Modest CNS stimulant with epileptogenic activity and cardiovascular
effects such as low blood pressure and a slowed heart rate.
Doses of cisatracurium are less to ever cause accumulation of
metabolite.
Cis atracurium is three times more potent than atracurium, so less
dose than atracurium.
Remifentanyl
Anilidopiperidine derivative.
Introduced in 1991.
Analgesic potency similar to fentanyl.
Ultra short acting.
Pharmacodynamics
CNS:
Concentration dependent slowing of EEG.
Muscle rigidity- bolus doses.
No effect on ICP.
Preserves cerebral autoregulation.
Dose dependent decrease in CPP.
No seizure activity.
Cardiovascular system
Dose dependent decrease in MAP.
Dose dependent bradycardia.
Respiratory system
Dose dependent respiratory depression.
Ventilatory response to CO2 is decreases by 50% of the baseline value.
Recovery from remifentanil- induced respiratory depression is rapid,
minute ventilation returns to baseline by 5-10 mins after the infusion is
stopped.
Gastrointestinal system
Nausea(44%) and vomiting (21%).
Delays gastric emptying and biliary drainage.
Pharmacokinetics
Smaller volume of distribution Vd- 100ml/kg.
Rapid clearance- 40ml/min/kg.
Metabolism by non specific esterases to inactive metabolites.
Distribution half life: 1 minute.
Elimination half life: 3-10 minutes.
Context- sensitive half life: 4 minutes- independent of the duration of
infusion.
Dosage and uses
Induction: 0.5-1 mcg/kg IV over 60 to 90 seconds.
Maintenance of anesthesia:
N2O(66%)+Isoflurane (0.4-1.5 MAC)
 Infusion Dose:0.05-0.2 mcg/kg/min
Propofol (100-200 mcg/kg/min)
Monitored anesthesia care.
Single dose: 0.5-1 mcg/kg over 30 to 60 seconds. Give 90 seconds
before the local anesthetics.
Continuous infusion beginning 5 mins before local anesthetics 0.1
mcg/kg/min after local anesthetics 0.05mcg/kg/min.
 Palonosetron
5-HT3 antagonist used in the prevention and treatment of
nausea and vomiting.
Given for delayed onset of nausea, vomiting post
chemotherapy.
It is considered more effective than Granisetron and studies are
to be done.
Given Intra venous, single dose, 30 minutes before
chemotherapy.
Mechanism of action
5-HT3 antagonist,.
Block Serotonin from binding to 5-HT3 receptor.
Adverse effects
Headache, sleeplessness
Constipation
First and Second degree atrioventricular block
Muscle pain
Shortness of breath.
Interactions
Serotonin syndrome when the drug is combined with serotonergic
antidepressants like SSRIs.
Pharmacokinetics
Orally taken, absorbed well, bioavailability of 97%.
Highest blood plasma levels reached after 5 to 6 hours.
Independent of food intake.
60% plasma protein bound.
60% metabolised by liver enzymes.
Excreted by the kidney.
Biological half life 37+/- 12 hours.