Atracurium Vecuronium Pancuronium

Non depolarising Agents made Easy

1. 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

2. ATRACURIUM

3. 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

4. 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

5. 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

6. Hofmann Elimination: (Cleave link between quarternary nitrogen ion and the central chain) Degrades to Laudanosine and a quarternary M onoacrylate . 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

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

8. 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

9. 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

10. 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

11. VECURONIUM

12. 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

13. 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

14. 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

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

16. 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

17. 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

18. PANCURONIUM

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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

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