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ATRACURIUM VECURONIUM PANCURONIUM

Presenter- Dr. Ranjith R ThampiDepartment of Anaesthesiology and Critical CareAmrita Institute of Medical Sciences, Kochi, Kerala

Non Depolarizing Muscle Relaxants

ATRACURIUM

Benzyl isoquinolinium ester

Presentation:Clear, colourless or pale yellow solutionAvailable 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

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/kgInitial dose of 0.5mg/kg relaxes for 15-35minsET intubation can be achieved within 90-120 seconds.Maintenance achieved with 0.1-0.2mg/kg boluses.Infusions: 0.3-0.6mg/kg/hrHypothermia(25 degrees) decreases metabolism95% recovery twitch height, following a single dose of atracurium within 35 minutes.

MECHANISM OF ACTION

Distribution:protein binding- 82% in plasmaDoes not cross BBBCrosses placenta but not in clinically significant amounts

Metabolism:2 pathways Hofmann degradation, NSE HydrolysisKINETIC

S

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.KINETIC

S

Excretion:Clearance is 5-6ml/kg/minElimination half life is 17-21mins

No dose adjustment required in renal and hepatic impairment

KINETICS

CVS- minimal<5% change in HR, MAP, SVR, CVP, PCWP

RSrisk 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

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

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

VECURONIUM

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

Competitive antagonism of Ach at Nicotinic receptors in post-synaptic membrane of NMJ. Also has some prejunctional action.

Routes of administration/ Doses:Administered intravenouslyED90 is 0.057mg/kgInitial dose of 0.1mg/kg provides relaxation for 25-40 minutes. ET intubation in 90-120 seconds95% recovery of twitch height within 45 minutes.Maintenance with boluses of 0.02- 0.03 mg/kgInfusion: 0.8-1.4 mcg/kg/min

Drug is non cumulative with repeated dosing.

MECHANISM OF ACTION

CVS- minimalin large doses- CO increases(9%), SVR decreases(12%)

RSlow 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

Rare reports of anaphylactoid reactionsCross sensitivity may exist with rocuronium and pancuronium.

PROBLEMS/ TOXICITY

Distribution:protein binding- 60-90% in plasmaDoes not cross BBBCrosses placenta but not in clinically significant amounts

Metabolism:Deacetylation in liver to active metabolites 3 and 17 OH and 3,17 di-OH- vecuroniumMetabolites have 50% potency of vecuroniumPresent in low concentrations, may be of clincial significance after prolonged dosing.

Excretion:Urine- 20-30% excreted unchangedBile- 20% unchanged, Metabolised drug is excreted in bile.Clearance- 3-6.4ml/kg/min, Elimination half life is 31-80 minutesRenal failure leads to prolongation of elimination half lifeHepatic failure leads to significant dose dependent decrease in clearance and increase in duration of action of drug.

KINETICS

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

PANCURONIUM

Bis Quarternary Amino Steroid

Presentation:Clear, colourless

2mg/ml of pancuronium bromide. Usually 2ml ampoule

pH- 4

CHEMICAL NATURE

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/kgInitial dose of 0.45-0.6 mg/kg relaxes for 65-100 minsET 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/kgInfusions: 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 3-6minsMECHANISM OF ACTION

Distribution:protein binding- 15-30% in plasmaDoes not cross BBBCrosses 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

Excretion:Decreases Triphasic manner40-50% excreted in urine5-10% in bile

Clearance is 1.10-2.22 ml/kg/minElimination half life is 69-161 mins

Dose adjustment needed in hepatic and renal impairment.

KINETICS

CVS-Increase in HR, BP, CO – secondary to vagolytic actionSVR remains unchanged.CVP may fall slightly.

RSLow 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

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

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

Thank You