1. Skeletal muscle relaxants
Prof. Hanan Hagar

2. By the end of this lecture, students should be able to:
Learning objectives
By the end of this lecture, students should be able to:
Identify classification of skeletal muscle relaxants
Describe the pharmacokinetics and dynamics of neuromuscular relaxants
Recognize the clinical applications for neuromuscular blockers
Know the different types of spasmolytics
Describe the pharmacokinetics and dynamics of spasmolytic drugs
Recognize the clinical applications for spasmolytic drugs

3. 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

4. Peripheral acting sk. M. relaxants Neuromuscular blockers
These drugs act by blocking neuromuscular junction or motor end plat leading to skeletal muscle relaxation.

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

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

8. Neuromuscular Junction

9. Competitive NM blockers
Have the suffix curium or curonium
Classified according to duration of action into:
Long acting
d-tubocurarine (proto type drug)
Pancuronium

10. Competitive NM blockers
Intermediate acting
Atracurium
Cisatracurium
Vecuronium
Rocuronium
Short acting
Mivacurium

11. Pharmacokinetics of competitive NM blockers
They are polar compounds
inactive orally & taken parenterally
Do not cross BBB (no central action)
Do not cross placenta
Metabolism depend upon kidney or liver
Except
Mivacurium (degraded by acetylcholinesterase )
Atracurium (spontaneous degradation in blood)

12. Pharmacological actions of competitive NMBs:
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 (constriction of bronchial smooth muscles).
Hypotension
Tachycardia

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

15. Mivacurium Chemically related to atracurium Fast onset of action
Short duration of action (15 min).
Metabolized by pseudo-cholinesterases.
Longer duration in patient with liver disease or genetic cholinesterase deficiency or malnutrition.
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 post-junctional 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 pseudo-cholinesterase in plasma
Half life is prolonged in
Neonates
Elderly
Pseudo-cholinesterase deficiency (liver disease or malnutrition or genetic cholinesterase deficiency).

21. Side Effects
Hyperkalemia
CVS arrhythmia
 Intraocular pressure contraindicated in glaucoma
Can produce malignant hyperthermia
May cause succinylcholine apnea due to deficiency of pseudo-cholinesterase.

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

23. 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

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

27. Spasmolytics
These drugs reduce muscle spasm produced by neurological disorders.
Classification
Centrally acting skeletal muscle relaxants
e.g. Baclofen – Diazepam
Direct acting skeletal muscle relaxants
e.g. Dantrolene

28. Central acting skeletal muscle relaxants
Baclofen:
Centrally acting
GABA agonist – acts on spinal cord.
Diazepam (Benzodiazepines):
facilitate GABA action on CNS.

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.
Orally, IV, (t ½ = hrs).
Uses
Malignant Hyperthermia.
Spastic states.

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

31. Alteration of responses
Increase in duration of action of skeletal muscle relaxants by diseases as:
Diseases
Myasthenia gravis
Kidney failure
Liver failure

32. Alteration of responses
Increase in duration of action of skeletal muscle relaxants by drugs as:
Drug interactions
General anesthetics
Aminoglycosides antibiotics ( e.g. gentamycin)
Anticonvulsants
Magnesium