Review of Pharmacology - 9E (2015)

Anaesthesia
Centrally Acting Muscle Relaxants
These drugs cause muscle relaxation by their action in the CNS. All these drugs can cause
sedation. Important drugs in this class are:
• Mephenesin group includes carisoprodol (its metabolite meprobamate is used as
a CNS depressant), chlorzoxazone, chlormezanone and methocarbamol. These drugs
selectively inhibit polysynaptic reflexes and are useful in local muscle spasms
like sprains and spasms due to spondylitis.
• Benzodiazepines like diazepam and clonazepam inhibit both polysynaptic as
well as monosynaptic reflexes and are useful in muscle spasms of almost any
origin. They are mainly used in spinal injuries and tetanus.
• GABA B
(It is a G protein coupled receptor unlike GABA A
, which is an ionotropic
receptor) agonists like baclofen increase K + conductance and can inhibit monosynaptic
as well as polysynaptic reflexes. Baclofen is used to relieve spasticity in multiple
sclerosis and spinal injuries. It is not useful in cerebral palsy.
• Tizanidine is a centrally acting α 2
agonist but unlike clonidine, has no effect
on blood pressure. It inhibits the release of excitatory neurotransmitters in the
spinal cord (by its presynaptic action). It can be used to relieve spasms in multiple
sclerosis, amyotrophic lateral sclerosis, other neurological disorders and spinal
injuries.
Dantrolene is the drug of choice
for the treatment of malignant
hyperthermia and is also
useful in neurolept malignant
syndrome.
Peripherally Acting Muscle Relaxants
These drugs do not enter the CNS and cause muscle relaxation by blocking neuromuscular
junction (neuromuscular blockers) or by acting directly on the muscle.
A. Directly Acting Skeletal Muscle Relaxants
• Dantrolene and quinine act directly on the skeletal muscles.
• Dantrolene inhibits the release of Ca ++ from sarcoplasmic reticulum via inhibition of
ryanodine receptors. It is used to relieve spasticity due to multiple sclerosis, cerebral
palsy and spinal cord injuries but is ineffective in spasms due to musculoskeletal
injuries. It is the drug of choice for the treatment of malignant hyperthermia
and is also useful in neurolept malignant syndrome. Major adverse effects of this
drug are muscle weakness and hepatitis.
• Quinine acts by decreasing the excitability of motor end plate and can be used in
patients with nocturnal leg cramps.
General Anaesthesia Pharmacology
B. Drugs Acting On Neuromuscular Junction (NMJ)
These drugs decrease the transmission of impulse across NMJ either by inhibiting nicotinic
N M
receptors or by consistently depolarizing the muscle end plate.
(a) Depolarizing Blockers
Succinylcholine (SCh) or suxamethonium is the only depolarizing SMR in use at present. It
is an ACh analogue and thus stimulates nicotinic N M
receptors resulting in depolarization of
the membrane. This effect is responsible for initial fasciculations seen on administration of
this agent (results in post operative muscle pain or soreness). Constant depolarization makes
the end plate refractory to other impulses and muscle relaxation results. It is a type of flaccid
paralysis that cannot be reversed with neostigmine (Phase I block). On prolonged use, this
block may be converted to phase II block that can be reversed with anticholinesterases.
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