An 18-year-old male was undergoing anesthesia for appendectomy. On administration of a muscle relaxant, a gradual fall in the blood pressure together with increased airway resistance was noticed. The airway resistance improved with the administration of diphenhydramine. The most likely muscle relaxant that was administered is

Answer: d) d-tubocurarineMUSCLE RELAXANTSDirectly actingNeuro muscular blocking agentCentrally acting agent* Dantrolene* QuinineDepolarizing (Non-competitive):* Succinyl choline/ Scoline/ Suxamethonium* DecamethoniumNon depolarizing (competitive):* Gantacurium * Mivacurium * Vecuronium, Rocuronium, Atracurium, Cisatracurium Others: Galamine, d-tubo curarine, Pancuronium, Pipecuronium, DoxacuriumActs on cerebrospinal axis without altering consciousness* Benzodiazepine* Mephensin* GABA derivatives as BaclofenDIRECT ACTING SKELETAL MUSCLE RELAXANTSDantrolene inhibits release of Ca2+ from sarcoplasmic reticulum, by inhibiting Ryanodine receptors.Dantrolene is DOC for malignant hyperthermia and neurolept malignant syndrome.S/E of Dantrolene - Muscle weakness and hepatitisQuinine is used to treat nocturnal leg cramps.NEURO MUSCULAR BLOCKING AGENTMaximum histamine release, contraindicated in Asthma: d-TCMinimum histamine release, used in Asthma: VecuroniumShortest acting non-depolarizing muscle relaxant = MivacuriumShortest acting depolarizing muscle relaxant = Succinyl cholineOverall shortest acting muscle relaxant = Succinyl cholineLongest acting Neuromuscular blocker = PancuroniumMost commonly used muscle relaxant = VecuroniumMost potent skeletal muscle relaxant = DoxacuriumLeast potent skeletal muscle relaxant = Succinyl cholineLeast potent Non-depolarising skeletal relaxant = RocuroniumMetabolized by pseudo cholinesterase: Succinyl choline & MivacuriumMuscle relaxant of choice in obstetrics & to decrease BP: d-Tubo curare (does not cross placenta)Muscle relaxant of choice to increase BP: PancuroniumMuscle relaxant with ganglion block: Curare, Galamine, Trimethaphan & PancuroniumFastest acting non-depolarising neuromuscular blockers - RocuroniumVagal & Ganglion stimulation caused by Succing cholineMaximal vagal block & Tachycardia- PancuroniumHistamine release & maximal vagal blockage- d -Tubocuramine Depolarizing blockNon depolarising blockEffect on single twitch heightDepressionDepressionTrain of four fadeAbsentPresentTetanic fadeAbsentPresentPost tetanic facilitationAbsentPresentEffect of anti cholinesterasePotentiation of blockReversal of blockEffect of non depolarizing agentLess blockadeMore blockadeSUCCINYL CHOLINEThe only depolarizing (noncompetitive) muscle relaxant in use.Rapid onset of action (30-60 seconds)Over all shortest duration of action (3-5 min) due to rapid hydrolysis by pseudo choline esterase.Succinylcholine is two acetylcholine molecules linked end-to-end.Scoline is metabolized completely into succinic acid + cholineDibucaine inhibits pseudo choline esterase activity.The percentage of inhibition of pseudo choline esterase activity is termed the dibucaine number.% of abnormal/normal pseudo choline esterase is determined by Dibucaine number & fluoride number.Under standardized test conditions, dibucaine inhibits the normal enzyme by 80% and the abnormal enzyme by only 20%.Dibucaine-resistant (variant) gene, is m/c recognized abnormal pseudocholinesterase genes.Normal Dibucaine no = 75 - 85.Drugs Known to Decrease Pseudocholinesterase ActivityDescriptionDrugOrganophosphate use for glaucomaEchothiophateCholinesterase inhibitorsNeostigmine,PyridostigmineMonoamine oxidase inhibitorPhenelzineAntineoplastic agentCyclophosphamideAntiemetic/prokinetic agentMetoclopramideB-BlockerEsmololNondepolarizing muscle relaxantPancuroniumVarious agentsOral contraceptivesScoline transiently increases muscle tone in the masseter musclesCauses dual or biphasic block with doses more than 500 mg Phase I BlockFeatures of classical depolarization blockPhase II BlockResults from desensitization of receptor to Ach. & resembles competitive / non -depolarization block and partially antagonized by anticholinesterasesClinical Responses and Monitoring of Phase I and Phase II Neuromuscular Blockade by Succinylcholine InfusionResponsePhase lPhase IIEnd-plate membrane potentialDepolarized to -55 mVRepolarization toward -80 mVOnsetImmediateSlow transitionDose-dependenceLowerUsually higher or follows prolonged infusionRecoveryRapidMore prolongedTrain of four and tetanic stimulationNo fadeFade*Acetylcholinesterase inhibitionAugmentsReverses or antagonizesMuscle responseFasciculations - flaccid paralysisFlaccid paralysis"Post-tetanic potentiation follows fade.Side effects:Increases muscle tone, Intraocular pressure, Intra-abdominal pressureMuscle fasciculation/Muscle soreness or acheHyperkalemia - diastolic cardiac arrest.Sudden Cardiac Arrest After Intubation And Succinylcholine - HyperkalemiaIncreases temperature i.e. Malignant HyperpyrexiaConditions causing susceptibility to Succinylcholine-induced Hyperkalemia* Burns* Massive trauma* Severe intraabdominal infection* Spinal cord injury* Encephalitis* Stroke* Guillain-Barre syndrome* Parkinson's disease , Polyneuropathy* Tetanus* Prolonged total body immobilization* Ruptured cerebral aneurysm* Closed head injury* Hemorrhagic shock with metabolic acidosis* Myopathies (eg, Duchenne's dystrophy)NONDEPOLARIZING MUSCLE RELAXANTSRelaxantChemical StructureMetabolismPrimary ExcretionHistamine ReleaseVagal BlockadeAtracuriumBenzyl-isoquinolone+++Insignificant+0Cisatracurium+++Insignificant00Mivacurium+++Insignificant+0DoxacuriumInsignificantRenal00PancuroniumSteroidal+Renal0++Pipecuronium+Renal00Vecuronium+Biliary00RocuroniumInsignificantBiliary0+ ATRACURIUMHofmann Elimination: Inactivated in plasma by spontaneous non enzymatic degradation & by choline esterases.Major metabolite - laudanosine (CNS stimulant) produce epileptiform fits.It's duration of action is not altered in patients with hepatic and renal in sufficiencyMuscle relaxant of choice in renal failure, anephric patients & liver diseaseHistamine release leading to flushing of skin.CISATRACURIUMUndergoes Hoffman elimination & also metabolized by kidneys.4-5 times more potent than atracuriumLaudanosine production is 5 times lesser than atracuriumPANCURONIUMCauses vagal blockade and releases noradrenaline.Produces tachycardia and hypertension.It is muscle relaxant of choice in shock and hypotension.It is metabolized by the kidney, so avoided in renal failure.VECURONIUMMost commonly used muscle relaxant for routine surgery.Most cardio stable. It is the muscle relaxant of choice for cardiac patients.Contraindicated in liver disease and in biliary obstruction.Causes polyneuropathy on long term use.PIPECURONIUMLong actingNo vagolytic activity (or) ganglion blockade activity.ROCURONIUMEarliest onset of action among non-depolarising muscle relaxant.Muscle relaxant of choice for pre-curarizationNon- depolarizing muscle relaxant of choice for intubation.ASYMMETRIC MIXED-ONIUM CHLOROFUMARATES (GANTACURIUM)Ultra short acting muscle relaxant.Degraded by two chemical mechanisms, neither of which is enzymatic:Rapid formation of an apparently inactive cysteine adduction product, with cysteine replacing chlorine.Slower hydrolysis of the ester bond adjacent to the chlorine substitution, presumably to inactive hydrolysis products.SUGAMMADEXSugammadex is the first selective relaxant binding agent.Sugammadex exerts its effect by forming very tight complexes in a 1:1 ratio with steroidal neuromuscular blocking agents (rocuronium > vecuronium >> pancuronium).Tubocurarine, the first muscle relaxant used clinically, produces hypotension and tachycardia through histamine release.Patients allergic to iodine (eg, shellfish allergies) could exhibit hypersensitivity to metocurine preparations as they too contain iodide.Gallamine has potent vagolytic properties and is entirely dependent on renal function for elimination.Rapacuronium is not used anymore because of severe bronchospasm.NOTE:d-Tubocurarine, atracurium, and mivacurium are non-depolarizing muscle relaxants, which are derived from benzylisoquinolinium compounds.These agents have a propensity to release histamine, with d-Tubocurarine having the highest propensity out of all the compounds.This results in greater predisposition to bronchoconstriction. However, this can be reversed with the administration of antihistaminics.The increased airway resistance is due to the presence of increased levels of histamine and administration of an antihistaminic such as diphenhydramine causes the reversal of the effects of histamine.d-Tubocurarine can block even the sympathetic ganglia.Histamine release along with sympathetic blockade can result in severe hypotension.