Skeletal muscle relaxants Prof. Hanan Hagar

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 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.

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): Centrally acting 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 = 8 - 9 hrs.