1. Skeletal muscle relaxants
Prof. Hanan Hagar

2. Skeletal muscle relaxants
Are drugs used to induce muscle relaxation
Classification
Peripherally acting (Neuromuscular blockers).
Centrally acting skeletal muscle relaxants
e.g. Baclofen - Diazepam
Direct acting skeletal muscle relaxants
e.g. Dantrolene

3. Neuromuscular blockers
Classification:
1) Competitive (non depolarizing blockers)
2) Depolarizing blockers

4. Binding of Ach to receptors on muscle end-plate

6. Neuromuscular Junction

7. Uses of neuromuscular blockers
Facilitate endotracheal intubation
Facilitate endoscopy
control convulsion  electroshock therapy in psychotic patient .
Relieve of tetanus and epileptic convulsion.
As adjuvant in general anesthesia to induce muscle relaxation
orthopedic surgery.

8. Muscle Relaxants Competitive (Nondepolarizing) muscle relaxants
Short acting
Intermediate acting
Long acting
Depolarizing muscle relaxant
Succinylcholine

9. Competitive NM blockers
Long acting
d-tubocurarine
Pancuronium
Intermediate acting
Atracurium
Cisatracurium
Vecuronium
Rocuronium
Short acting
Mivacurium

10. Competitive NM blockers
Mechanism of Action
Are competitive antagonists
Compete with Ach for the nicotinic receptors present in postjunctional membrane of motor end plate.
No depolarization of postjunctional membrane

11. Pharmacokinetics
They are polar compounds
inactive orally & taken parenterally
Do not cross placenta & CNS
Metabolism depend upon kidney or liver
Except
Mivacurium (degraded by acetylcholinesterase )
Atracurium (spontaneous degradation in blood)

12. Pharmacological actions:
Skeletal muscle relaxation.
They produce different effects on CVS
Some release histamine and produce hypotension
d.Tubocurarine
Atracurium
Mivacurium
Others produce tachycardia ( H.R)
Pancuronium

13. d – Tubocurarine Long duration of action (1 - 2 hr)
Eliminated by kidney 60% - liver 40%.
Releases histamine that causes:
Bronchospasm
Hypotension
Tachycardia

14. Atracurium As potent as curare (1.5)
Has intermediate duration of action (30 min).
Eliminated by non enzymatic chemical
degradation in plasma (spontaneous hydrolysis at body pH, Hofmann elimination).
used in liver failure & kidney failure (drug of choice).
Liberate histamine  (Transient hypotension)

15. Mivacurium Chemically related to atracurium Fast onset of action
Metabolized by pseudo cholinesterases.
Short duration of action (15 min).
Longer duration in patient with liver disease or genetic cholinesterase deficiency.
Transient hypotension (due to histamine release).

16. Pancuronium Excreted by the kidney ( 80 % ). Long duration of action.
More potent than curare ( 6 times ).
Excreted by the kidney ( 80 % ).
Long duration of action.
Side effects : hypertension, tachycardia
 NE release from adrenergic nerve endings.
Antimuscarinic action (block parasympathetic action)

17. Vecuronium More potent than tubocurarine ( 6 times ).
Metabolized mainly by liver.
Intermediate duration of action.
Has few side effects.
No histamine release.
No tachycardia.

18. Depolarizing Neuromuscular Blockers
Mechanism of Action
combine with nicotinic receptors in postjunctional membrane of neuromuscular junction  initial depolarization of motor end plate  muscle twitching  Persistent depolarization  relaxation

19. Succinylcholine (suxamethonium)
Pharmacological Actions
SK. muscle : initial contraction followed by relaxation.
Hyperkalemia : Cardiac arrest.
Eye :  intraocular pressure.
CVS : arrhythmia

20. Pharmacokinetics
Fast onset of action (1 min.).
Short duration of action (5-10 min.).
Metabolized by pseudocholinesterase in plasma
Half life is prolonged in
Neonates
Elderly
Pseudcholinesterase deficiency (liver disease –
malnutrition).

21. Side Effects
Hyperkalemia
CVS arrhythmia
 IOP # glaucoma
Can produce malignant hyperthermia
May cause succinylcholine apnea due to deficiency of pseudocholinesterase.

22. Notes Side effects Duration Drug Tubocurarine Pancuronium Atracurium
# Renal failure
Hypotension
Long
1-2 h
Tubocurarine
# Renal failure
Tachycardia
Pancuronium
Spontaneous degradation
Used in liver and kidney failure
Transient hypotension
Histamine release
Short
30 min.
Atracurium
# Liver failure
Few side effects
40 min.
Vecuronium
Metabolized by pseudocholinesterase
# Choline esterase deficiency
Similar to atracurium
15 min.
Mivacurium
# CVS Diseases
# Glaucoma
# Liver disease
Hyperkalemia
Arrhythmia
Increase IOP
10 min.
Succinyl
choline

25. Alteration of responses
Diseases
Myasthenia gravis
Kidney failure
Liver failure
Drug interactions
Inhalation & Intravenous anesthetics
Aminoglycosides antibiotics
Anticonvulsants
Magnesium

26. Malignant hyperthermia
Is a rare inherited condition that occurs upon administration of drugs as:
general anesthesia e.g. halothane
neuromuscular blockers e.g. suxamethonium
Inability to bind calcium by sarcoplasmic reticulum in some patients due to genetic defect
 Ca release, intense muscle spasm, hyperthermia

27. Spasmolytics They reduce muscle spasm in spastic states Baclofen:
Centrally acting
GABA agonist – acts on spinal cord.
Diazepam (Benzodiazepines):
facilitate GABA action on CNS.
Dantrolene:
direct action on skeletal muscles.
Used in treatment of malignant hyperthermia

28. Uses of spasmolytics
They reduce muscle spasm in spastic states produced by :
Spinal cord injury
Cerebral stroke
Cerebral palsy

29. Dantrolene Mechanism of Action
It interferes with the release of calcium from its stores in skeletal muscles (sarcoplasmic reticulum).
It inhibits excitation-contraction coupling in the muscle fiber.
Uses
Malignant Hyperthermia.
Spastic states.
IV, orally t ½ = hrs.