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Skeletal Muscle Relaxants

Depolarizing Agent
Succinylcholine (suxamethonium)
polar (given parenterally)
Short half-life
Rapidly hydrolysed by plasma cholinesterase
Small fraction reach NMJ (neuromuscular junction)
Action terminated by diffusion away into ECF
MOA
Phase I (Depolarizing)
Phase II (Desensitising)
Prolonged stimulation of nicotinic
Due to continued expos ure to
receptors
succinylcholine

Initially causing depolarization

Repolarization occur

Spread of AP

Membrane cannot be easily

depolarized again

Muscle contraction
desensitisation
(fasciculation)
Membrane remain depolarized

Similar to blockade by
nondepolarising agents

Unresponsive to subsequent
impulse

Reversed by anticholinesterase

Flaccid paralysis
Block augmented by
anticholinesterases

Rapid onset (30-60 se c)

Short duration (<10 min)
Duration prolonged by

Dose

Abnormal metabolism
o
Hypothermia
o
pseudocholinesterase (pregnancy, liver disease, renal failure,
drugs)
o
Genetic


Heterozygous (20-30 min)


Homozygous (4 -8 hours)
Side effects

Hyperkalaemia

Intraocular pressure

Intragastric pressure

Muscle pain (post-op unsynchronised muscle contraction)

Bradycardia

Intracranial pressure

Malignant hyperthermia

Nondepolarizing Agent
Pancuronium, Vecuronium, Atracurium, Cisatracurium, Rocuronium
polar (given parenterally)
Excreted via kidney - half-life
Metabolised by liver - half-life
Steroidal agent produce active metabolite accumulate in long term admins
MOA

Compete with ACh at binding sites

Do not depolarize motor end plate

Competitive antagonist

Excessive conce ntration cause channel blockade

Act at presynaptic sites prevent Ach movement to release sites

Pancuronium
Eliminated
mainly
kidney - 85%
Liver - 15%
Side effects
Hypertension
Tachycardia
Dysrhythmia

Vecuronium
Eliminated
mainly liver
- 60%
Kidney 40%
Vagoly@c

Atracurium
Metabolism
Hofmann
elimination
Ester
hydrolysis
Side effects
Hypotension
Tachycardia
Bronchos pasm

Cisatracurium
Metabolism
Hofmann
elimination

Rocuronium
Eliminated
mainly liver
Kidney
slightly

CVS side
effects

Drug interactions

Inhalation agents

Intravenous anesthetics

Local anesthetics

Neuromuscular blocking drugs

Antibiotics aminoglycosides
Anticholinesterases

Reverse effect of nondepolarizing muscle relaxants

Neostigmine, Pyridostigmine, Edrophonium

MOA
o
Inhibit acetylcholinesterase


ACh available at NMJ


Compete for sites at receptors
o
Action at muscarinic receptor


Bradycardia


Hypersecretion


intes@nal tone

Muscarinic side effects mini mized by anticholinergic agents

o
Atropine
o
Scopolamine
o
Glycopyrrolate

Spasmolytic agents
Benzodiazepines , Baclofen, Dantrole ne
Benzodiazepines

Diazepam

Clonazepam

MOA
Facilitate GABA action in CNS
Causes sedation

Dantrolene

Hydantoin derivative

Interfere with excitationcontraction coupling in

muscle fibres

muscle strength

Use in malignant
hyperthermia

Baclofen

Activate GABA receptors

Oral, Intrathecal

sedative than
benzodiazepine

Cause muscle weakness

Withdrawal precipitate
seizures (in epileptics)
Botulinum toxin

Prevent release of ACh

Injection spastic muscles

Effects weeks - months