11. Muscle relaxants Flashcards
Muscle relaxants
-drugs that decrease skeletal muscle tone
-used to treat muscle hypertonicity (central muscle relax) or decrease physiological tone of skeletal muscle (anesthesiology)
-2 groups->.central vs peripheral acting
central muscle relaxants
-used for muscle hypertonicity
-affects nerve excitement EARLIER THAN ON THE NMJ
MoA of central muscle relaxants
-varies depending on the representative
-inhibits polysynaptic signals at INTRANEURONAL SPINAL CORD LEVEL
-potentitate inhibition-> main inhibitory neurotransmitter in CNS -> GABA
-attenuate excitation -> main excit NT-> GLUTAMATE
how are the central muscle relaxants classified
benzos vs non benzos
what are the benzos
Diazepam
what are the non benzos
baclofen
tolperisone
tizanidine
thiocolchicoside
orphenadrine
guaifenesin
mephenoxalone
Cannabis sativa with defined content of THC and CBD (cannabidiol)
Diazepam -properties
muscle relaxant
anticonvulsant
anxiolytic
sedative
hypnotic
Diazepam action
-potentiated inhibition - (increased GABA at inhib synapse) -> anticonvuls and muscle relax
-increased gaba leads to attenuated excitation -Glut-> anxiolytic and hypnosedative
benzodiazepine receptors
BZD1 rc- anxiolytic and hypnosedative
BZD2- anticonvuls, muscle relax
Baclofen
-structural analogue of GABA
-agonist of GABA rcp- acts on level of spinal cord
-reduces monosynaptic and polysynpatic reflex transmissions in spinal cord by stimulating GABA B receptors
-inhibits release of excitatory amino acids
-acts mainly presynaptically -> reduces excitability of motorneuron
Tolperison
-similar chem structure to lidocaine
inhib action at level of reflex spinal pathway
-stabilising effect on cell membranes-reduces electrical excitability of motor neurons
-inhibits influx of Na+ membrane isolated nerve cells -> reduces amplitude and frequency of action potentials
-inhib action of ca2+ voltage gated channels-> reduces NT release
-weak alpha antag and antimusc properties
Tizanidine
-acts on spinal cord -> inhibits polysynaptic signals at interneuronal level-> reduces muscle tone
- inhibits release of excitatory amino acids stimulating NMDA receptors by stimulating presynaptic alpha receptors
-shows a mild analgesic effect
-high individual variability
Thicolchicoside
- a colchicine analog with muscle relaxant pharm activity
-acts as an agonist of GABA A receptors
orphenadrine
-block M and NMDA rcp in CNS
-affects the transmission in nerve impulses from spinal cord to muscle -> muscle relaxation
-shows locally anaesthetic and weak antihistamine properties
guaifenasin
-antagonises NMDA recep
-causes anxiolytic and expectorant effects
risk of overuse
mephenoxalone
-inhibits of neuronal transmission at level of reflex arc
Delta 9 tetrahydrocannabinol( THC )and cannabidiol (CBD)
from cannabis sativa
oral spray
used to improve symps in MS (mild to moderate spasticity)
for pts who have improved after an initial trial treatment in spasticity
How are peripheral muscle relaxants classified
-by their action
-direct mechanism (botulinum toxin) vs indirect mechanism (non depolarising vs depolarising)
what is the moa of non depolarising peripheral muscle relaxants ?
competitive antagonism at NM rcp. of
neuromuscular junction → Na+ channels will NOT
open → depolarization will NOT occur → muscle
contraction will NOT occur
do non depolarising p.m relax have antidote
yes- ache inhibitors abolish the action
what is the moa of depolarising peripheral muscle relaxants ?
non-competitive agonism at NM rcp.of
neuromuscular junction → Na+ channels open →
depolarization occurs → muscle contraction occurs
briefly but Na+ channels remain LONG inactive
state, agonist is degraded longer than ACh → rcp.
are blocked, new stimulation is not possible which
leading to relaxation
There is NO antidote- Ache inhibitors slow down the degradation and therefore increase the effect
what are the depolarising peripheral muscle relaxants
suxamethonium
what are the non depolarising peripheral muscle relaxants
pipecuronium
atracurium
rocuronium
mivacurium
Pk of peripheral muscle relaxants
NOT ABSORBED ORALLY
ONLY INJECTION
does not cross BBB-> consciousness not affected
clinical use of peripheral muscle relaxants
General anaesthesia
-application until the introduction
CONTROLLED LUNG VENTILATION NEEDED ( diaphragm will also relax)
-muscle relaxation before intubation (urgent in injuries and accidents)
Succinylcholine=suxamethonium
-the only depolarising muscle relaxant used
fast onset , short effect (intubation and short term intervention
what are the AE of suxamethonium
bradycardia
increased intraocular pressure and intracranial pressure
increased K+
malignant hyperthermia
prolonged paralysis
CI of suxamethonium
bradycardia - bradycardia
crrush syndrome -(because of increased K+)
glaucoma -increased ICP and IOP
history of malig hyperthermia (malignant hyperthermia)
Tubocurarine
-arrow poison
-rapid onset
short half life
long acting
AE- sudden histamine release, sudden BP drop , bronchospasm-> so it is replaced with a better representative with shorter duration of action
long acting non depolarising p.m relaxant
pipercuronium - has a fast onset
medium acting non depolarising p.m. muscle relaxant
rocuronium - fast onset , indication: INTUBATION
vercuronium
short acting non depolarising p.m. muscle relaxant
mivacurium -> degraded by cholinesterase
what are the AE of non depolarising peripheral muscle relaxants ?
Resemble an allergic reaction:
―histaminoliberation
―hypotension
―bronchospasm
―bronchial secretion and salivation
―myopathy (in accumulation)
―ganglion blockade contributes to
postoperative atony of the GIT and urinary tract
Agents used to reverse the non depolarising peripheral muscle relaxants
sugammadex
neostigmine
dantrolene
sugammadex
-causes the cancellationn of the rocuronium induced neuromuscular blockade
-binds selectively to steroid muscle relaxant-> forms an inactive plasma complex-> which is excreted unchanged in the urine
-causes fast cancellation of muscle relaxation and fewer. side effects than using NEOSTIGMINE
neostigmine
an acetylcholinesterase
-used to antagonise the non depolarising periph muscle relax effect
dantrolene mechanism of action and indication
moa - direct, by binding to ryanodine rcp. 1 of the sarcoplasmic reticulum blocks the
release of Ca2+ into the cytosol → prevents contraction directly in the myocyte
indication -malignant hyperthermia and malig neuroleptic syndrome
-must be given before all Ca2+ is released
what is malignant hyperthermia
-rare congenital AE with high mortality rate
-caused by mutation in the Ca2+ channel of the sarcoplasmic reticulum (ryanodine receptors) -> leads to intense muscle cramps
-leads to sudden increase in body temp after admin of certain substances
what is the most common cause of malignant hyperthermia
suxamethonium
how is malignant hyperthermia treated
-dantrolene
- a substance that inhibits muscle contractions by preventing the release of Ca2+ from sarcoplasmic reticulum
