This document summarizes three non-depolarizing muscle relaxants: atracurium, vecuronium, and pancuronium. It describes the chemical nature, mechanism of action, kinetics including metabolism and excretion, effects, problems/toxicity, and special considerations for each drug. Atracurium is metabolized primarily through Hofmann elimination and NSE hydrolysis. Vecuronium undergoes deacetylation in the liver to active metabolites. Pancuronium undergoes up to 45% hepatic metabolism with subsequent biliary excretion. All three drugs act as competitive antagonists at nicotinic receptors in the neuromuscular junction.

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ATRACURIUM
VECURONIUM
PANCURONIUM
Presenter- Dr. Ranjith R Thampi
Department of Anaesthesiology and Critical Care
Amrita Institute of Medical Sciences, Kochi, Kerala
Non Depolarizing Muscle Relaxants

5. ATRACURIUM

6.  Benzyl isoquinolinium ester
 Presentation:
Clear, colourless or pale yellow solution
Available as 2.5ml, 5ml, and 25ml vials
containing 10mg/ml of atracurium besilate,
needs to be stored at 2-8 degrees.
 pH- 3.25- 3.65
CHEMICAL NATURE

7.  Acts by competitive antagonism of Ach at Nicotinic receptors at the post-
synaptic membrane of the NMJ.
 Routes of Administration:
Intravenously. ED95 is 0.23 mg/kg
Initial dose of 0.5mg/kg relaxes for 15-35mins
ET intubation can be achieved within 90-120 seconds.
Maintenance achieved with 0.1-0.2mg/kg boluses.
Infusions: 0.3-0.6mg/kg/hr
Hypothermia(25 degrees) decreases metabolism
95% recovery twitch height, following a single dose of atracurium within
35 minutes.
MECHANISM OF ACTION

8.  Distribution:
protein binding- 82% in plasma
Does not cross BBB
Crosses placenta but not in clinically
significant amounts
 Metabolism:
2 pathways
Hofmann degradation, NSE Hydrolysis
KINETICS

9.  Hofmann Elimination:
(Cleave link between quarternary nitrogen
ion and the central chain)
Degrades to Laudanosine and a quarternary
Monoacrylate.
Laudanosine primarily cleared by the liver.
 NSE Hydrolysis:
minor pathway, hydrolysed to a quarternary
alcohol and a quarternary acid.
*Metabolites have no neuromuscular blocking
activity.
KINETICS

10.  Excretion:
Clearance is 5-6ml/kg/min
Elimination half life is 17-21mins
 No dose adjustment required in
renal and hepatic impairment
KINETICS

12.  CVS- minimal
<5% change in HR, MAP, SVR, CVP, PCWP
 RS
risk of BRONCHOSPASM(secondary to
histamine release) in 0.2% patients.
 CNS- No effect on ICP, IOP
 AS- LES pressure is unaffected by atracurium
DYNAMIC EFFECTS

13.  Histamine release can occur with doses
>0.6mg/kg- cutaneous flushing, hypotension,
bronchospasm
 Rarely, anaphylactoid reactions
 In ICU patients, associated with development
of critical illness neuropathy/myopathy
PROBLEMS/ TOXICITY

14.  Prolongation of duration of action:
hypokalemia, hypocalcemia, hypermagnesemia, hypoproteinemia,
dehydration, acidosis, hypercapnia
 Promoting Drugs:
Isoflurane(35%), Ketamine, Fentanyl, Scoline, Diuretics, CCBs, alpha and
aminoglycosides
 Decelerating Drugs:
patients on c/c anticonvulsant therapy
*safe in patients susceptible to malignant hyperpyrexia
 Cisatracurium- less histamine release
 Acidic pH Atracurium- should not be mixed with alkaline
solutions(barbiturates)
SPECIALS

15. VECURONIUM

16.  Chemical- bis-quarternary aminosteroid (analogue to
pancuronium)
 Presentation:
Lyophilized powder containing- citric acid
monohydrate(20.75mg), disodium hydrogen phosphate
dihydrate(16.25mg), mannitol(170mg), sodium hydoxide or
phosphoric acid.
 Diluted in water or NS prior to use to yield a clear, colourless,
isotonic solution containing 2mg/ml of vecuronium bromide,
Solution is stable for 24hours.
CHEMICAL NATURE

17.  Competitive antagonism of Ach at Nicotinic receptors in post-synaptic
membrane of NMJ. Also has some prejunctional action.
 Routes of administration/ Doses:
Administered intravenously
ED90 is 0.057mg/kg
Initial dose of 0.1mg/kg provides relaxation for 25-40 minutes.
ET intubation in 90-120 seconds
95% recovery of twitch height within 45 minutes.
Maintenance with boluses of 0.02- 0.03 mg/kg
Infusion: 0.8-1.4 mcg/kg/min
Drug is non cumulative with repeated dosing.
MECHANISM OF ACTION

18.  CVS- minimal
in large doses- CO increases(9%), SVR
decreases(12%)
 RS
low potential for histamine release; bronchospasm
is extremely uncommon
 CNS- No effect on ICP, IOP
 AS- LES pressure remains unaltered
 Metabolic/other
Decreases PTT, PT
DYNAMIC EFFECTS

19.  Rare reports of anaphylactoid
reactions
Cross sensitivity may exist with
rocuronium and pancuronium.
PROBLEMS/ TOXICITY

20.  Distribution:
protein binding- 60-90% in plasma
Does not cross BBB
Crosses placenta but not in clinically significant amounts
 Metabolism:
Deacetylation in liver to active metabolites 3 and 17 OH and 3,17 di-OH-
vecuronium
Metabolites have 50% potency of vecuronium
Present in low concentrations, may be of clincial significance after prolonged
dosing.
 Excretion:
Urine- 20-30% excreted unchanged
Bile- 20% unchanged, Metabolised drug is excreted in bile.
Clearance- 3-6.4ml/kg/min, Elimination half life is 31-80 minutes
Renal failure leads to prolongation of elimination half life
Hepatic failure leads to significant dose dependent decrease in clearance and
increase in duration of action of drug.
KINETICS

22.  Prolongation of duration of action:
hypokalemia, hypocalcemia, hypermagnesemia,
hypoproteinemia, dehydration, acidosis, hypercapnia
 Promoting Drugs:
Isoflurane(35%), Ketamine, Fentanyl, Scoline, Diuretics,
CCBs, alpha and beta adrenergic antagonists,
protamine, lidocaine, metronidazole, aminoglycosides
 Burns patients may develop resistance to vecuronium
 Length of onset of action and duration may be
prolonged in patients on chronic anticonvulsant
therapy. Safe in patients susceptible to malignant
hyperpyrexia.
 Reversal- Neostigmine only after TOF of 4 twitches
 Sugammadex (gamma- cyclodextrin) can be used to
reverse effects. (conc. Gradient)
SPECIALS

23. PANCURONIUM

24.  Bis Quarternary Amino Steroid
 Presentation:
Clear, colourless
 2mg/ml of pancuronium bromide.
Usually 2ml ampoule
pH- 4
CHEMICAL NATURE

25.  Acts by competitive antagonism of Ach at Nicotinic receptors at the post-
synaptic membrane of the NMJ. *Also has some pre-junctional action.
 Routes of Administration:
Intravenously. ED95 is 0.05 mg/kg
Initial dose of 0.45-0.6 mg/kg relaxes for 65-100 mins
ET intubation can be achieved within 90-150 seconds.
Maintenance achieved with 0.01-0.02 mg/kg boluses.
*If administered after suxamethonium, iv dose to be reduced to 0.02-0.06 mg/kg
Infusions: NOT RECOMMENDED
Intramuscularly- 1mg/kg for infants and 2mg/kg for children to produce VC and
diaphragmatic palsy for intubation. But not fully effective until after 3-6mins
MECHANISM OF ACTION

26.  Distribution:
protein binding- 15-30% in plasma
Does not cross BBB
Crosses placenta but not in clinically significant amounts
 Metabolism:
30-45% undegoes hepatic metabolism by deacetylation to 3-
OH-, and 17-OH-, and 3,17- OH derivatives with subsequent
biliary excretion.
 3-OH derivative has half neuromuscular blocking activity of
parent drug compared to other metabolites
KINETICS

28.  Excretion:
Decreases Triphasic manner
40-50% excreted in urine
5-10% in bile
Clearance is 1.10-2.22 ml/kg/min
Elimination half life is 69-161 mins
 Dose adjustment needed in hepatic and
renal impairment.
KINETICS

29.  CVS-
Increase in HR, BP, CO – secondary to vagolytic action
SVR remains unchanged.
CVP may fall slightly.
 RS
Low potential for Histamine release; BRONCHOSPAM
extremely uncommon
 CNS- No effect on ICP, IOP
 AS- salivation slightly increased
 Metabolic/Other- May dcrease PTT and PT
DYNAMIC EFFECTS

30.  Rarely, anaphylactoid reactions
 Cross sensitivity with vecuronium and rocuronium
 At transient rash may occur following administration of
pancuronium.
 CONTRAINDICATIONS:
 -Ascites, Asthma, Breastfeeding, Cardiac disease,
Pulmonary Diseases, Hepatic Disease, Neuromuscular
Disorders.
PROBLEMS/ TOXICITY

31.  Prolongation of duration of action:
hypokalemia, hypocalcemia, hypermagnesemia,
hypoproteinemia, dehydration, acidosis, hypercapnia
 Promoting Drugs:
Isoflurane(35%), Ketamine, Fentanyl, Scoline, Diuretics,
CCBs, Alpha and Beta adrenergic antagonists, protamine,
lidocaine, metronidazole, aminoglycosides
 *safe in patients susceptible to malignant hyperpyrexia
SPECIALS

32. Thank You