Skeletal muscle relaxants

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• Skeletal muscle relaxants
• Prof. Hanan Hagar

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• 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

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• 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

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

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• Neuromuscular blockers
• Classification
• 1) Competitive (non depolarizing blockers)
• 2) Depolarizing blockers

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• 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

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Neuromuscular Junction
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Competitive NM blockers

• Have the suffix curium or curonium
• Classified according to duration of action into
• Long acting
• d-tubocurarine (proto type drug)
• Pancuronium

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Competitive NM blockers

• Intermediate acting
• Atracurium
• Cisatracurium
• Vecuronium
• Rocuronium
• Short acting
• Mivacurium

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• 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)

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• 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

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• 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

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• 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).

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• 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).

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• 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)

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

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• 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

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

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• 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).

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

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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

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

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• 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

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

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• 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 8 - 9 hrs).
• Uses
• Malignant Hyperthermia.
• Spastic states.

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

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Alteration of responses

• Increase in duration of action of skeletal muscle
  relaxants by diseases as
• Diseases
• Myasthenia gravis
• Kidney failure
• Liver failure

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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