SKELETAL MUSCLES RELAXANTS

1. SKELETAL MUSCLE
RELAXANTS
LECTURE # 5

2. CLINICAL IMPORTANCE
In conjugation with General Anesthetics:
1.Facilitate intubation of the trachea
2.Facilitate mechanical ventilation
3.Optimized surgical working conditions

3. CLASSIFICATION
 The centrally acting
 Peripherally acting:
1. Drugs acting directly on skeletal muscles
2. Drugs Acting on Neuro Muscular Junction (NMJ)
A) DEPORALIZING BLOCKERS
B) NON DEPOLARIZING BLOCKERS (LONG, SHORT AND INTERMEDIATE
ACTING)
C) OTHERS

5. Physiology of Skeletal Muscle
Contraction

6. Acetylcholine
Acetylcholine is a major transmitter at autonomic,
somatic and central nervous system:
1. All preganglionic sites (Both Parasympathetic and
sympathetic)
2. Skeletal Muscles
3. CNS: Cortex Basal ganglia, spinal cord and others

7. Neuromuscular Junction (NMJ)

9. Peripherally acting:
Neuromuscular Blockers
 Depolarizing Blockers (Act on open channels)
Succinylcholine is an ultra-short-acting depolarizing muscle relaxant,
which binds to motor endplate cholinergic receptors to produce
depolarization.
Since the depolarization is sustained, the electrical activity of the
motor endplate is lost, leading to paralysis.

11. Non-Depolarising Drugs
Act on closed channels

12. Mechanism of Action
They have affinity for Nicotinic receptors
(Antagonist)
They are quaternary N+ compounds act only
on closed Na+ channels –
No action on already opened Na+ channels

13. The cationic head binds to the anionic ACh binding
site at the subunit of the Nm receptor but cannot
bring conformational change & Na+ channels
remains closed
Muscle Action Potential decreases
Action can be overcome by increased ACh
concentration or blocking of acetylcholinesterase
Mechanism of Action

14. Mechanism of Action:
Non-depolarizing Block in Muscles

16. Non-Depolarising Drugs
Competitive Blockers (antagonist)
• These are of 3 types based on their activity:
– Long Acting : d-TC, Pancuronium, Pipecuronium,
Gallamine (Kidney Excretion)
– Intermediate : Vecuronium, Rocuronium,
Atracuronium (eliminated by liver)
– Short Acting : Mivacuronium, Ropcacuronium
(inactivated by plasma cholinesterase)

17. Effects of Non-depolarizing blockers
Low Doses:
– Competitive antagonists of ACh
– Action reversed by ACh ecterase inhibitors

18.  Large Doses:
– Ion Channel is blocked
– More weakness of neuromuscular transmission
– Action could not be reversed by ACh esterase inhibitors
 Other actions:
– Can block pre-junctional Na+ channels and interfere with
mobilization of ACh at nerve endings

19. Non-depolarizing Drug:
 Gallamine
– Less potent than curare
– Tachycardia

20.  D-Tubocurarine
– 1-2 hr duration of action
– Histamine releaser (Bronchospasm, hypotension)
– Blocks autonomic ganglia (Hypotension)
 Atracurium
– Rapid recovery
– Safe in hepatic & renal impairment
– Spontaneous inactivation to laudanosine (seizures)

21. Mivacurium
 – Metabolized by
pseudocholinesterase
 – Fast onset and short duration
Pencuronium
 – Long duration of action
 – Tachycardia

22. Vecuronium
 – Intermediate duration of action
 – Fewer side effects (no histamine release, no ganglion
 blockade, no antimuscarinic action)

24. Directly acting relaxants - Dantrolene
Different from neuromuscular blockers, no action on
neuromuscular transmission
Mechanism of Action:
1. Depresses excitation-contraction coupling in
skeletal muscle by binding to the ryanodine
receptor 1,
2. Decreasing intracellular calcium concentration.

25. Ryanodine receptors mediate the
release of calcium from the sarcoplasmic
reticulum, an essential step in muscle
contraction.

26. The sarcoplasmic reticulum (SR)
a specialized form of the
endoplasmic reticulum of muscle
cells, dedicated to calcium ion
(Ca2+) handling, necessary for
muscle contraction and relaxation.

28. Dantrolene
 Absorbed orally, penetrate brain and produces sedation,
metabolized in liver, excreted in kidney.
 T1/2 8-12 hrs
 Dose: 25-100mg - 4 times daily
 Uses: Upper Motor Neuron disorders – paraplegia,
hemiplegia, cerebral palsy and malignant hyperthermia (drug
of choice 2.5-4 mg/kg)
 Adverse effects – Sedation, malaise, light headedness,
muscular weakness, diarrhoea and hepatotoxicity

29. The centrally acting muscle relaxants
MECHANISM OF ACTION
1. Facilitation of the action of gamma aminobutyric
acid (GABA), an inhibitory neurotransmitter in
the central nervous system.
2. This results in the sedative, hypnotic (sleep-
inducing), anxiolytic (anti-anxiety),
anticonvulsant (Anti-seizure), and muscle
relaxant properties

31. Diazepam and midazolam are centrally acting
muscle relaxants that are frequently combined with
opioids to produce calming and muscle relaxation
before surgery.
The centrally acting muscle relaxants

33. SIDE EFFECTS/Other Actions of Nm
Blockers
Automic ganglia:
 Partial blockage of ganglia (Nm type of receptor)
 Results in fall in BP and tachycardia
Histamine release:
 Hypotension

34.  Bronchospasm, excess bronchial and salivary
secretion
Cardiovascular: Fall in BP due to
 Ganglion blockage, histamine release and
reduced venous return
 Succinylcholine may cause cardiac arrhythmias
SIDE EFFECTS/Other Actions of Nm
Blockers

35. Classification