Muscle

Relaxants
I Wayan Sumardika
Pharmacology Department
Faculty of Medicine, Udayana
University
 Muscle Relaxants
 Facilitate intubation of the
trachea
 Facilitate mechanical ventilation

 Optimized surgical working

conditions
 Reduce abnormally elevated tone

by neurologic or muscle end plate

diseases
Muscle Relaxants
 Muscle relaxants must not be
given without adequate dosage
of analgesic and hypnotic drugs

 Inappropriately given : a patient

is paralyzed but not anesthetized
Muscle Relaxants
 Mechanism of Action
 Neuromuscular junction
 Nerve terminal
 Motor endplate of a muscle
 Synaptic cleft
 Nerve stimulation
 Release of Acetylcholine (Ach)
 Postsynaptic events
Neuromuscular Junction
(NMJ)
Binding of Ach to receptors on muscle end-
plate
Neuromuscular
Blocking Drugs
 Depolarizing muscle relaxant
 Succinylcholine
 Nondepolarizing muscle
relaxants
 Short acting
 Intermediate acting
 Long acting
 Depolarizing Muscle
Relaxant
 Succinylcholine
 Pharmacokinetics
 Metabolized by plasma cholinesterase
 Not metabolized locally at NMJ
 Physically resemble Ach
 Rapid onzet of action
 Mechanism of Action
 Act like nicotinic agonist and depolarize the
neuromuscular end plate
 Initial depolarization: twicthing and fasciculations
 Continuous end-plate depolarization causes
muscle relaxation
 Neuromuscular
Blocking Drugs
 Reversal of Blockade
 Action of Non depolarizing blockers reversed by
increasing the cooncentration of transmitter at
the receptor
 Accomplised by administration of cholinesterase
inhibitors (neostigmine, pyridostigmine)
 Paralysis produced by depolarizing blockers
increased by cholinesterase inhibitors during
phase I. During phase II, the block produced by
succinilcholine is ussually reversible by
cholinesterase inhibitors
 Neuromuscular
Blocking Drugs
 Toxicity
 Respiratory paralysis Mechanical
ventilation
 Autonomic effect and histamine release
 Specific effect of succinylcholine
hypercalemia
 Interaction

Inhaled anesthetics, potentiate and prolong
neuromuscular blockade

Aminoglycoside and antiarrhytmic drugs
Nondepolarizing Muscle
Relaxants
 Long acting
 Pancuronium
 Intermediate acting
 Atracurium
 Vecuronium
 Rocuronium
 Cisatracurium
 Short acting
 Mivacurium
 Nondepolarizing Muscle
Relaxants
 Pharmacokinetic
 Agents that metabolized or eliminated in the bile have shorter
duration of action than those eliminated by the kidney.
 Mechanism of Action
 Compete with Ach at the binding sites
 Do not depolarized the motor endplate
 Act as competitive antagonist
 Excessive concentration causing channel blockade
 Act at presynaptic sites, prevent movement of Ach to
release sites
Nondepolarizing Muscle
Relaxants
 Pancuronium
 Aminosteroid compound
 Onset 3-5 minutes, duration 60-90
minutes
 Intubating dose 0.08-0.12 mg/kg
 Elimination mainly by kidney (85%),
liver (15%)
 Side effects : hypertension, tachycrdia,
dysrhythmia,
Nondepolarizing Muscle
Relaxants
 Vecuronium
 Analogue of pancuronium
 much less vagolytic effect and shorter
duration than pancuronium
 Onset 3-5 minutes duration 20-35 minutes
 Intubating dose 0.08-0.12 mg/kg
 Elimination 40% by kidney, 60% by liver
Nondepolarizing Muscle
Relaxants
 Atracurium
 Metabolized by
 Ester hydrolysis

Hofmann elimination
 Onset 3-5 minutes, duration 25-35 minutes
 Intubating dose 0.5 mg/kg
 Side effects :
 histamine release causing hypotension, tachycardia,
bronchospasm
 Laudanosine toxicity
Nondepolarizing Muscle
Relaxants
 Cisatracurium
 Isomer of atracurium
 Metabolized by Hofmann elimination
 Onset 3-5 minutes, duration 20-35
minutes
 Intubating dose 0.1-0.2 mg/kg
 Minimal cardiovascular side effects
 Much less laudanosine produced
Nondepolarizing Muscle
Relaxants
 Rocuronium
 Analogue of vecuronium
 Rapid onset 1-2 minutes, duration 20-
35 minutes
 Onset of action similar to that of
succinylcholine
 Intubating dose 0.6 mg/kg
 Elimination primarily by liver, slightly
by kidney
Antagonism of
Neuromuscular
Blockade
Effectiveness of anticholinesterases depends
on the degree of recovery present when they
are administered
 Anticholinesterases
 Neostigmine
 Onset 3-5 minutes, elimination halflife 77

minutes
 Dose 0.04-0.07 mg/kg

 Pyridostigmine
 Edrophonium
Antagonism of
Neuromuscular
Blockade
 Mechanis of action
 Inhibiting activity of acetylcholineesterase
 More Ach available at NMJ, compete for
sites on nicotinic cholinergic receptors
 Action at muscarinic cholinergic receptor
 Bradycardia
 Hypersecretion
 Increased intestinal tone
Antagonism of
Neuromuscular
Blockade
 Muscarinic side effects are
minimized by anticholinergic
agents
 Atropine

Dose 0.01-0.02 mg/kg
 Scopolamine
 glycopyrrolate
 SPASMOLYTIC DRUGS
 Diseases of the CNS (cerebral palsy,
multiple sclerosis)
 Abnormal high reflex activity in the neural
pathways that control skeletal muscle
 Painful spasm
 Therapy: reduction of excessive sceletal
muscle tone without reduction of strength.
 Drugs for Chronic Spasm
 Act in the CNS or in the sceletal
muscle cell rather than at the NMJ
 Diazepam
 Baclofen
 Tizanidine
 Dantrolene
 Mechanism of Action
 Diazepam---facilitates GABA-mediated
presynaptic inhibition
 Baclofen---acts as a GABA agonist causing
membrane hyperpolarization via increased K+
conductance
----decrease the release of excitatory
neurotransmiter
 Tizanidine---significant Alpha 2 agonist activity,
reinforce both presynaptic and postsynaptic
inhibition in the cord
 Dantrolene---reduce the release of
activator calcium from the
sarcoplasmic reticulum
 Effective in the treatment of
malignant hypertermia (massive
calcium release from the
sarcoplasmic reticulum of skeletal
muscle)
 Drugs for Acute Muscle
Spasm
 Treatment of acute spasm resulting
from muscle injury
 Sedative or act in the brain stem or
spinal cord
 Cyclobenzaprine
 Antimuscarinic actions
 Cause confusion and visual hallucination