11. Muscle relaxants

Question 1

Muscle relaxants

Answer 1

-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

Question 2

central muscle relaxants

Answer 2

-used for muscle hypertonicity
-affects nerve excitement EARLIER THAN ON THE NMJ

Question 3

MoA of central muscle relaxants

Answer 3

-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

Question 4

how are the central muscle relaxants classified

Answer 4

benzos vs non benzos

Question 5

what are the benzos

Answer 5

Diazepam

Question 6

what are the non benzos

Answer 6

baclofen
tolperisone
tizanidine
thiocolchicoside
orphenadrine
guaifenesin
mephenoxalone
Cannabis sativa with defined content of THC and CBD (cannabidiol)

Question 7

Diazepam -properties

Answer 7

muscle relaxant
anticonvulsant
anxiolytic
sedative
hypnotic

Question 8

Diazepam action

Answer 8

-potentiated inhibition - (increased GABA at inhib synapse) -> anticonvuls and muscle relax

-increased gaba leads to attenuated excitation -Glut-> anxiolytic and hypnosedative

Question 9

benzodiazepine receptors

Answer 9

BZD1 rc- anxiolytic and hypnosedative
BZD2- anticonvuls, muscle relax

Question 10

Baclofen

Answer 10

-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

Question 11

Tolperison

Answer 11

-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

Question 12

Tizanidine

Answer 12

-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

Question 13

Thicolchicoside

Answer 13

• a colchicine analog with muscle relaxant pharm activity
  -acts as an agonist of GABA A receptors

Question 14

orphenadrine

Answer 14

-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

Question 15

guaifenasin

Answer 15

-antagonises NMDA recep
-causes anxiolytic and expectorant effects
risk of overuse

Question 16

mephenoxalone

Answer 16

-inhibits of neuronal transmission at level of reflex arc

Question 17

Delta 9 tetrahydrocannabinol( THC )and cannabidiol (CBD)

Answer 17

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

Question 18

How are peripheral muscle relaxants classified

Answer 18

-by their action
-direct mechanism (botulinum toxin) vs indirect mechanism (non depolarising vs depolarising)

Question 19

what is the moa of non depolarising peripheral muscle relaxants ?

Answer 19

competitive antagonism at NM rcp. of
neuromuscular junction → Na+ channels will NOT
open → depolarization will NOT occur → muscle
contraction will NOT occur

Question 20

do non depolarising p.m relax have antidote

Answer 20

yes- ache inhibitors abolish the action

Question 21

what is the moa of depolarising peripheral muscle relaxants ?

Answer 21

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

Question 22

what are the depolarising peripheral muscle relaxants

Answer 22

suxamethonium

Question 23

what are the non depolarising peripheral muscle relaxants

Answer 23

pipecuronium
atracurium
rocuronium
mivacurium

Question 24

Pk of peripheral muscle relaxants

Answer 24

NOT ABSORBED ORALLY
ONLY INJECTION
does not cross BBB-> consciousness not affected

Question 25

clinical use of peripheral muscle relaxants

Answer 25

General anaesthesia -application until the introduction CONTROLLED LUNG VENTILATION NEEDED ( diaphragm will also relax) -muscle relaxation before intubation (urgent in injuries and accidents)

Question 26

Succinylcholine=suxamethonium

Answer 26

-the only depolarising muscle relaxant used fast onset , short effect (intubation and short term intervention

Question 27

what are the AE of suxamethonium

Answer 27

bradycardia increased intraocular pressure and intracranial pressure increased K+ malignant hyperthermia prolonged paralysis

Question 28

CI of suxamethonium

Answer 28

bradycardia - bradycardia crrush syndrome -(because of increased K+) glaucoma -increased ICP and IOP history of malig hyperthermia (malignant hyperthermia)

Question 29

Tubocurarine

Answer 29

-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

Question 30

long acting non depolarising p.m relaxant

Answer 30

pipercuronium - has a fast onset

Question 31

medium acting non depolarising p.m. muscle relaxant

Answer 31

rocuronium - fast onset , indication: INTUBATION vercuronium

Question 32

short acting non depolarising p.m. muscle relaxant

Answer 32

mivacurium -> degraded by cholinesterase

Question 33

what are the AE of non depolarising peripheral muscle relaxants ?

Answer 33

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

Question 34

Agents used to reverse the non depolarising peripheral muscle relaxants

Answer 34

sugammadex neostigmine dantrolene

Question 35

sugammadex

Answer 35

-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

Question 36

neostigmine

Answer 36

an acetylcholinesterase -used to antagonise the non depolarising periph muscle relax effect

Question 37

dantrolene mechanism of action and indication

Answer 37

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

Question 38

what is malignant hyperthermia

Answer 38

-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

Question 39

what is the most common cause of malignant hyperthermia

Answer 39

suxamethonium

Question 40

how is malignant hyperthermia treated

Answer 40

-dantrolene - a substance that inhibits muscle contractions by preventing the release of Ca2+ from sarcoplasmic reticulum