Download CENTRAL Muscle Relaxants

MUSCLE RELAXANTS
Peripheral vs central muscle relaxants
CENTRAL
Muscle Relaxants
Classification

benzodiazepines vs non-benzodiazepines (syn. others)

benzodiazepines
 tetrazepam and diazepam (not approved in this indication in the
Czech Rep.)

non-benzodiazepines
 baclofen, carisoprodol, orphenadrine, thiocolchicoside,
tizanidine and tolperison
 mephenoxalon and guaifenesin have also anxiolytic effects
 dantrolen is used for the treatment of malignant hyperthermia
Mechanism of action

relaxation of skeletal muscles

MA:

potentiation of GABAergic transmission (benzodiazepines, baclofen (acts as a GABA-B
agonist) etc.)

stimulation of alpha-2 adrenergic receptors => decreased release of mediators to
synaptic cleft (tizanidine etc.)

stimulation of glycinergic transmission (thiocolchicoside)

tolperison inhibits voltage-gated sodium channels

tolperison and its derivatives (eperison, lanperison, inaperison and silperison) dosedependently inhibit potentials of ventral spinal roots and decreases the activity of motor
neurons; it also blocks voltage-gated calcium ion channels in afferent pathways for pain
(result: analgesia)

mefenoxalon decreases muscle tonus by inhibition of polysynaptic supraspinal reflex
arch

dantrolen blocks calcium release from sarcoplasmic reticulum => dissociation of
excitation and contraction of skeletal muscles
Indications

acute back pain caused by spasms of
skeletal muscle

chronic painful conditions but for short-term
use only

additive effect with NSAIDs or paracetamol
(carisoprodole + paracetamol; orphenadrine
+ diclofenac)
PERIPHERAL
Muscle Relaxants
Muscle Relaxants
 What
are they used for?
Facilitate intubation of the
trachea
 Facilitate mechanical ventilation
 Optimized surgical working
conditions

Neuromuscular Junction (NMJ)
Muscle Relaxants

Depolarizing muscle relaxant


Succinylcholine
Nondepolarizing muscle relaxants



Short acting
Intermediate acting
Long acting
Depolarizing Muscle Relaxant


Succinylcholine
What is the mechanism of action?






Physically resemble Ach
Act as acetylcholine receptor agonist
Not metabolized locally at NMJ
Metabolized by pseudocholinesterase in plasma
Depolarizing action persists > Ach
Continuous end-plate depolarization causes
muscle relaxation
Depolarizing Muscle Relaxant

Succinylcholine
 Does it has side effects?








Cardiovascular
Fasciculation
Muscle pain
Increase intraocular pressure
Increase intragastric pressure
Increase intracranial pressure
Hyperkalemia
Malignant hyperthermia
Nondepolarizing Muscle
Relaxants

What is the 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

Long acting


Intermediate acting





Pancuronium
Atracurium
Vecuronium
Rocuronium
Cisatracurium
Short acting

Mivacurium
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