Pharmacology Skeletal Muscle Relaxant.pdf

Pharmacology Year 1 MBBS skeletal muscle relaxtant

1. 17. (Pharm) Skeletal Muscle Relaxant


Drug acting at Neuromuscular Junction
Non-depolarizing / Competitive
Mechanism of Action Non-depolarising blocking agents act as competitive antagonists at the nicotinic Ach receptors of the endplate.
Effects -The effects of non-depolarising neuromuscular-blocking agents are mainly due to motor paralysis, although some of the drugs also
produce clinically significant autonomic effects.
-The first muscles to be affected are the extrinsic eye muscles and the small muscles of the face, limbs and pharynx.
-Respiratory muscles are the last to be affected and the first to recover.
Uses Maintain neuromuscular relaxation throughout an operation which may be of several hours duration or when unconscious in an
intensive care unit.
Pharmacokinetics -Minimally absorbed when given orally
-Vecuronium and Rocuronium and metabolites appear mainly in bile
-Most drugs excreted primarily unchanged in urine
Drugs Tubocurarine Pancuronium Vecuronium Atracurium Mivacurium
Speed of Onset Slow (>5 min) Intermediate (2–3 min) Intermediate Intermediate Fast (∼2 min)
Duration of action Long (1–2 h) Long (1–2 h) Intermediate (30–40 min) Intermediate (<30 min) Short (∼15 min)
Side Effects Hypotension
(ganglion block plus
histamine release)
Bronchoconstriction
(histamine release)
Slight tachycardia,
Hypertension
-Widely used
(Few Side effects)
prolonged paralysis, probably owing to active
metabolite Rocuronium
is similar, with faster
onset
Transient hypotension
(histamine release)
Transient hypotension
(histamine release)
rapidly inactivated by
plasma cholinesterase
(therefore longer acting in
patients with liver disease
or with genetic
cholinesterase deficiency)
Depolarizing Neuromuscular-blocking Drug
Drug Succinylcholine or Suxamethonium
Mechanism of Action -Acts by depolarisation of endplate (nicotinic agonist effect)
-Succinylcholine attaches to the nicotinic receptor and acts like ACh to depolarize the junction
Phase I – Depolarizing
First causes the opening of the sodium channel associated with the nicotinic receptors, which results in depolarization of the receptor.
This leads to a transient twitching of the muscle (fasciculations).
Phase II – Desensitization
Continued binding of the depolarizing agent renders the receptor incapable of transmitting further impulses. With time, continuous
depolarization gives way to gradual repolarization as the sodium channel closes or is blocked. This causes a resistance to
depolarization and flaccid paralysis.

Speed of Onset Fast
Duration of action Short (∼10 min)
Uses Used for brief procedures (e.g. tracheal intubation, electroconvulsive shock therapy), induction of anaesthesia
Side Effects -Bradycardia (muscarinic agonist effect) Cardiac dysrhythmias (increased plasma K+ concentration – avoid in patients with burns or
severe trauma)
-Raised intraocular pressure (nicotinic agonist effect on extraocular muscles)
-Postoperative muscle pain, malignant hyperthermia (rare)
-Short duration of action owing to hydrolysis by plasma cholinesterase (prolonged action in patients with liver disease or genetic
deficiency of plasma cholinesterase)

Neuromuscular Blocking Agents
- Drugs can block neuromuscular transmission either
by acting presynaptically to inhibit ACh synthesis or
release, or by acting postsynaptically.
- Important adjunct to anaesthesia
- Except suxamethonium, all of the drugs used
clinically are non-depolarising agents

Central
-Diazepam
-Baclofen

Peripheral
-Drugs acting at Neuromuscular junction (NMJ)
▪ Non-Depolarizing/ Competitive
→Tubocurarine
→Vecuronium
→Atracurium
→Mivacurium
▪ Depolarizing
▪ Others
-Drugs directly acting on skeletal muscle



Characteristics of Non-depolarising vs Depolarising
Non-depolarising block is reversible by anticholinesterase drugs, depolarising block is not.

2. 17. (Pharm) Skeletal Muscle Relaxant

Scoline apnoea (Condition)
▪ Administration of succinylcholine to a patient who is
deficient in plasma cholinesterase or who has an
atypical form of the enzyme can lead to prolonged
apnea due to paralysis of the diaphragm.
▪ The rapid release of potassium may also contribute to
prolonged apnea in patients with electrolyte imbalances who receive this drug.
▪ In patients with electrolyte imbalances who are also
receiving digoxin or diuretics (such as heart failure patients) succinylcholine should be used cautiously or
not at all.

Pharmacogenetic basis
▪ Genetic variants of plasma cholinesterase with
reduced activity
▪ Severe deficiency, enough to increase the duration
of action to 2h or more, occurs in approximately 1 in
3500 individuals.
▪ Very rarely, the enzyme is completely absent and
paralysis lasts for many hours.
▪ Biochemical testing of enzyme activity in the
plasma and its sensitivity to inhibitors is used
clinically to diagnose this problem; genotyping is
possible but as yet not practicable for routine screening
to prevent the problem.

Treatment
Mechanical ventilation

Dantrolene
Mechanism of action
-Direct acting muscle relaxant
-Directly prevents excitation-contraction coupling by
decreasing calcium
-Release from sarcoplasmic reticulum
Uses
-Malignant hyperthermia
-Neuroleptic malignant syndrome
-Spasticity of upper motor neurone lesion
-Cerebral palsy
-Multiple sclerosis
Side Effects
Weakness, hepatotoxicity, euphoria, dizziness and
drownsiness
Centrally acting muscle relaxants
Drugs Diazepam Baclofen
-derivative of GABA (inhibitory
neurotransmitter)
Mechanism of action ▪ Enhances the effect of GABA, an inhibitory
neurotransmitter in CNS at the level of spinal
cord
▪ Enhances the presynaptic inhibition of
afferent neuronal terminals in the primary
reflex arc
▪ Stimulates GABA-B receptor in the spinal
cord and decreases the release of excitatory neurotransmitters
Uses ▪ Cerebral palsy
▪ Spasticity due to spinal cord lesions
▪ Spasticity due to multiple sclerosis
▪ Spasticity due to traumatic lesions spinal cord
Side effects ▪ CNS depressant effect
▪ Hangover effect
▪ Tolerance and drug dependence


Others skeletal muscle relaxants
▪ Botulinum toxin and β -bungarotoxin, act specifically to inhibit Ach release.
▪ Botulinum toxin is a protein produced by the anaerobic bacillus Clostridium botulinum, an organism that can multiply in preserved
food and can cause botulism, an extremely serious type of food poisoning.