Skeletal Muscle RelaxantsFACULTY OF PHARMACYUNIVERSITY OF SANTO TOMAS

Skeletal Muscle RelaxantsDivided into 2 dissimilar groupsNeuromuscular blocking agentsAct at the skeletal myoneural junction to produce muscle paralysis to facilitate surgery or artificial ventilation

Skeletal Muscle RelaxantsDivided into 2 dissimilar groupsSpasmolytic drugsAct on the CNS to reduce abnormally elevated tone caused by neurologic or muscle endplate disease

Skeletal Muscle RelaxantsTubocurarineMivaricuriumBaclofenDiazepamTizanidineDantroleneCyclobenzaprineSuccinylcholine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSClassification and prototypesSkeletal muscle contractionEvoked by a nicotinic cholinergic transmission processBlockade of transmission at the skeletal muscleendplate (postsynaptic structure bearing thenicotinic receptors) Produces relaxation of muscleA requirement for surgery

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSClassification and Prototypes Neuromuscular blockersQuaternary aminesStructurally related to acetylcholine (ACh) Nondepolarizing typeNicotinic antagonist TubocurarineDepolarizing typeNicotinic agonist Succinylcholine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSClassification and Prototypes Neuromuscular blockersNondepolarizing typeSubclassified depending on chemical structureIsoquinoline derivativesAtracuriumcisatracuriumDoxacuriummetocurineMivacuriumtubocurarine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSClassification and Prototypes Neuromuscular blockersNondepolarizing typeSubclassified depending on chemical structureSteroid derivativesPancuroniumPiperacuroniumRocuroniumVecuronium

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsPharmacokineticsAll drugs are given IVDrugs metabolized by plasma cholinesteraseMivacurium (shortest duration of action)Drugs eliminated in the bile have shorter duration of actionVecuronium

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsPharmacokineticsAll drugs are given IVDrugs eliminated by the kidney PancuroniumTubocurarine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsPharmacokineticsAtracurium clearanceHoffman eliminationRapid spontaneous breakdown to form laudanosine and other productsIndependent of hepatic or renal function

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsPharmacokineticsCisatracuriumStereoisomer of atracuriumLess dependence oh hepatic metabolismForms less laudanosineLess likely to release histamineFewer side effects

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsMechanism of actionPrevent the action of ACh at the skeletal muscle endplateAct as surmountable blockersOvercomed by increasing the amount of agonist

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSNondepolarizing neuromuscular blocking drugsMechanism of actionCompete with ACh at the receptor siteEffect is reversed by cholinesterase inhibitors

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSDepolarizing neuromuscular blocking drugsPharmacokinetics SuccinylcholineComposed of 2 ACh moleculesMetabolized by the plasma cholinesterase(butyrylcholinesterase or pseudocholinesterase)Duration of action of only a few minutes if given as a single dose

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSDepolarizing neuromuscular blocking drugsPharmacokinetics SuccinylcholineBlockade may be prolonged in patients with genetic variants of plasma cholinesterase Metabolizes the drug very slowly Not rapidly hydrolyzed by acetylcholinesterase

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSDepolarizing neuromuscular blocking drugsMechanism of actionAct like nicotinic agonistsDepolarize the neuromuscular end plateParalysis that results from persistent depolarization of the end plate

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSDepolarizing neuromuscular blocking drugsMechanism of actionInitial depolarizationTwitching and fasciculationsContinuous depolarizationMuscle relaxation and paralysis

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSDepolarizing Neuromuscular Blocking DrugsMechanism of actionContinuous infusionChanges from continuous depolarization(phase I) to gradual repolarization withresistance (phase II)

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSReversal of blockadeNondepolarizing blockersReversed by increasing the concentrationof normal transmitter at the receptorsAdministration of cholinesterase inhibitorsNeostigmine and physostigmine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSReversal of blockadeDepolarizing blockersPhase I (Continuous depolarization)Paralysis is increased by cholinesteraseinhibitorsPhase II (Desensitization)Membrane cannot easily be depolarized againReversed by cholinesterase inhibitors

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSToxicityRespiratory paralysisFull doses leads directly to respiratoryparalysisMechanical ventilation should be provided to avoid asphyxiation

Drug Effect on autonomic ganglia Effect on cardiac muscarinic receptors Ability to release histamine Nondepolarizing isoquinoline derivatives Atracurium

None

None

Slight CisatracuriumNone None None Mivacurium None None Moderate Tubocurarine Weak block None Moderate Nondepolarizing steroid derivatives Pancuronium

None

Moderate block

None RocuroniumNoneSlightNone Vecuronium None None None Depolarizing Succinylcholine StimulationStimulationSlight

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSToxicityAutonomic effects and histamine releaseAutonomic ganglia Stimulated by succinylcholineBlocked by tubocurarine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSToxicityAutonomic effects and histamine releaseHistamine releaseOccur with tubocurarineTo a slight extent with atracurium,mivacurium, and succinylcholine

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSToxicitySpecial effects of succinylcholineMuscle pain is a common postoperative complaint Muscle damage may occurStimulates cardiac muscarinic receptors Pancuronium is a moderate blocker

Skeletal Muscle RelaxantsNEUROMUSCULAR BLOCKING DRUGSToxicitySpecial effects of succinylcholineHyperkalemia in patients Burn or spinal cord injuryPeripheral never dysfunctionMuscular dystrophyIncreases in intragastric pressure Promotes emesis

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSPainful spasms Associated with abnormally high reflexactivity Control of skeletal muscle is affected Bladder and anal sphincter control is also affected

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSPainful spasms Chronic diseases of the CNS Cerebral palsyMultiple sclerosisStroke Acute injuryInflammation of muscle

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSGoal in both acute and chronic conditionsReduction of excessive skeletal muscle tone without reduction of strengthReduced spasm results in reduction of pain and improved mobility

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasmClassificationDo not resemble ACh in structure or effectAct in the CNS or in the skeletal muscle than in the neuromuscular endplateAll given oral

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsDiazepam BenzodiazepineFacilitates GABA-mediated presynapticinhibition

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsBaclofenGABA agonist causing membranehyperpolarization Increased K+ conductanceDecreases the release of excitatory neurotransmitters including substance P

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsTizanidineImidazoline related to clonidineWith significant alpha2 agonist activityReinforces both presynaptic and post-synaptic inhibition in the spinal cord

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsDantroleneActs on the sarcoplasmic reticulum of the skeletal muscle by reducing the release of activator Ca+2

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsDantroleneMalignant hyperthermiaMassive release of Ca+2 Uncontrolled contraction and stimulation of metabolism in the skeletal muscleGeneral anesthesia protocols with succinylcholine and tubocurarine

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsBotulinum toxinInjected to selected muscles to prevent the release of ACh in order to reduce pain caused by severe spasm

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm Classification and mechanisms of actionsGabapentinAntiseizure drugStructural analogue of GABAEffective in multiple sclerosis

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for chronic spasm ToxicityBaclofen Less sedating than diazepamDantrolene Muscle weaknessLess sedating than diazepam or baclofen Tizanidine Hypotension and drowsiness

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for acute muscle spasmPromoted for treatment of acute spasmresulting from muscle injurySedatives that act in the brain or spinal cord

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for acute muscle spasmCyclobenzaprineActs in the brain stem by interfering with the post synaptic reflexes that maintain skeletal muscle toneGiven oral

Skeletal Muscle RelaxantsSPASMOLYTIC DRUGSDrugs for acute muscle spasmCyclobenzaprineMarked sedative and muscarinic actionsMay cause confusion, visual hallucinationsNot effective in muscle spasm resultingfrom cerebral palsy or spinal cord injury