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    Skeletal Muscle Relaxants JJ

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    Fachrul Aq
    Skeletal muscle relaxants are classified as peripherally or centrally acting. Peripherally acting drugs include neuromuscular blockers that work presynaptically to inhibit acetylcholine synthesis/release or postsynaptically as competitive or depolarizing blockers. Centrally acting drugs like baclofen and diazepam facilitate muscle relaxation by acting on the spinal cord or brain. Dantrolene acts directly on skeletal muscles to interfere with calcium release and excitation-contraction coupling. These drugs find uses for muscle spasms, convulsions, and to facilitate procedures under anesthesia by inducing relaxation. Their mechanisms, pharmacokinetics, side effects and clinical applications are described.

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    Skeletal Muscle Relaxants JJ

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    Fachrul Aq
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    Skeletal muscle relaxants are classified as peripherally or centrally acting. Peripherally acting drugs include neuromuscular blockers that work presynaptically to inhibit acetylcholine synthesis/release or postsynaptically as competitive or depolarizing blockers. Centrally acting drugs like baclofen and diazepam facilitate muscle relaxation by acting on the spinal cord or brain. Dantrolene acts directly on skeletal muscles to interfere with calcium release and excitation-contraction coupling. These drugs find uses for muscle spasms, convulsions, and to facilitate procedures under anesthesia by inducing relaxation. Their mechanisms, pharmacokinetics, side effects and clinical applications are described.

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    Skeletal muscle relaxants are classified as peripherally or centrally acting. Peripherally acting drugs include neuromuscular blockers that work presynaptically to inhibit acetylcholine synthesis/release or postsynaptically as competitive or depolarizing blockers. Centrally acting drugs like baclofen and diazepam facilitate muscle relaxation by acting on the spinal cord or brain. Dantrolene acts directly on skeletal muscles to interfere with calcium release and excitation-contraction coupling. These drugs find uses for muscle spasms, convulsions, and to facilitate procedures under anesthesia by inducing relaxation. Their mechanisms, pharmacokinetics, side effects and clinical applications are described.

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    63 views28 pages

    Skeletal Muscle Relaxants JJ

    Uploaded by

    Fachrul Aq
    Skeletal muscle relaxants are classified as peripherally or centrally acting. Peripherally acting drugs include neuromuscular blockers that work presynaptically to inhibit acetylcholine synthesis/release or postsynaptically as competitive or depolarizing blockers. Centrally acting drugs like baclofen and diazepam facilitate muscle relaxation by acting on the spinal cord or brain. Dantrolene acts directly on skeletal muscles to interfere with calcium release and excitation-contraction coupling. These drugs find uses for muscle spasms, convulsions, and to facilitate procedures under anesthesia by inducing relaxation. Their mechanisms, pharmacokinetics, side effects and clinical applications are described.

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    Skeletal muscle relaxants

    Classification

    Peripherally acting (Neuromuscular blockers). Centrally acting Sk. M. relaxants Baclofen - Diazepam Direct acting Sk. M. relaxants. Dantrolene

    Peripherally acting A) Presynaptic neuromuscular blockers 1) Inhibit Ach synthesis Triethylacholine - hemicholinium 2) Inhibit Ach release Mg, aminoglycosides, botulinum toxin, B) Postsynaptic neuromuscular blockers 1) Competitive (non depolarizing blockers) 2) Depolarizing blockers

    Postsynaptic Neuromuscular Blockers


    Competitive NM blockers d-tubocurarine Gallamine Atracurium Pancuronium Vecuronium Depolarizing NM blockers Succinylcholine (suxamethonium )

    Uses of NMB blockers


    control convulsion electroshock therapy in psychotic patient . Relieve of tetanus and epileptic convulsion. facilitate endoscopy As adjuvant in general anesthesia to induce muscle relaxation orthopedic surgery.

    Competitive NM blockers
    Mechanism of Action competitive antagonists: compete with Ach at the Nicotinic receptors of NMJ. No depolarization of postjunctional membrane. Cholinesterase inhibitors can reverse blockade (Neostigmine).

    Pharmacokinetics

    They are polar comp.

    inactive orally &taken parenterally.


    No cross placenta & CNS

    Metabolism depend upon kidney or liver EXCEPT

    atracurium - mivacurium (cholinesterase).

    Pharmacological actions

    Skeletal muscle relaxation.

    CVS
    H.R Gallamine Pancuronium

    Hypotension (Histamine release) d.Tubocurarine Mivacurium Atracurium

    Gallamine ( Flaxedil ) Less potent than curare ( 1/5 ).

    Metabolized mainly by kidney 100% # in renal failure

    Long duration of action.


    Tachycardia due to :

    Atropine like action. Release of NA from adrenergic nerve endings.

    d Tubocurarine

    More potent than gallamine


    Long duration of action ( 1 - 2 hr. ) Eliminated by kidney 60% - liver 40%. Histamine releaser

    Bronchospasm

    Hypotension

    Blocks autonomic ganglia (Hypotension)

    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).

    used in liver failure & kidney failure ( drug of choice ). Liberate histamine ( Transient hypotension ). No effect on muscarinic receptor nor ganglia .

    Mivacurium

    Chemically related to atracurium


    Metabolized by pseudo cholinesterases. Fast onset of action Short duration of action (15 min). Transient hypotension (histamine release).

    Longer duration in patient with liver disease or genetic cholinesterase deficiency.

    Pancuronium More potent than curare ( 6 times ).

    Excreted by the kidney ( 80 % ).


    Long duration of action. Tachycardia

    Antimuscarinic action

    NE release from adrenergic nerve endings.

    Vecuronium More potent than tubocurarine ( 6 times ).


    Metabolized

    mainly by liver.
    duration of action.

    Intermediate Has

    few side effects. histamine release. ganglion block.

    No No No

    antimuscarinic action.

    Depolarizing Neuromuscular Blockers Mechanism of Action

    Phase I ( Depolarizing )

    combine with nicotinic receptors depolarization of motor end plate initial muscle twitching Persistent depolarization paralysis.
    Phase I block is augmented not reversed by anticholinestrases.

    Phase II ( Desensitization Block )


    Continuous exposure to succinylcholine depolarization decreases and the membrane become repolarized, but the membrane cannot be depolarized by Ach as long as succinylcholine present desensitization of the membrane. This phase reversed by anticholinesterase.

    Succinylcholine ( suxamethonium )
    Pharmacological Actions
    1.

    2.

    3.
    4.

    5.

    SK. muscle : fasciculation spastic paralysis. Hyperkalemia : Cardiac arrest. Eye : intraocular pressure. GIT : intragastric pressure regurgitation of gastric content to esophagus. CVS : arrhythmia

    Pharmacokinetics
    Short onset of action ( 1 min. ). Short duration of action (5-10 min.). Destroyed by pseudocholinesterase

    Side Effects

    Hyperkalemia. CVS arrhythmia (Bradycardia, extrasystol and cardiac arrest ). IOP # glaucoma Malignant hyperthermia. Succinylcholine apnea due to ? liver disease (neonates elderly). Malnutrition Organophosphorous poisoning.

    Drug Tubocurarine Gallamine Pancuronium

    Duration Long (1 h) Long Long

    Side effects Hypotension Tachycardia Muscarinic antagonist Tachycardia Antimuscarinic action Few side effects

    Notes # Renal failure Renal excretion # Renal failure # Renal failure

    Vecuronium Atracurium

    short short

    # Liver failure

    Transient hypotension Spontaneous Histamine release degradation Used in liver and kidney failure Less histamine release

    Cisatracurium

    Short

    Mivacurium

    Similar to atracurium Metabolized by plasma choline esterases # Choline esterase deficiency

    Suxamethonium

    Short

    Hyperkalemia Arrhythmia Increase IOP

    CVS Diseases Glaucoma Liver disease

    Spasmolytics

    Baclofen:

    Centrally acting (GABA agonist Sp. cord).


    Diazepam (Benzodiazepines):

    Centrally acting (facilitate GABA action on Sp. Cord & CNS).


    Dantrolene: direct action on sk. muscles.

    Uses of spasmolytics
    reduce muscle spasm in Spinal cord injury Stroke Cerebral palsy

    Dantrolene Mechanism of Action 1. It interferes with the release of calcium from its stores in sk. muscles (sarcoplasmic reticulum). 2. It inhibits excitation-contraction coupling in the muscle fiber. Uses Malignant Hyperthermia. Spastic states. IV, orally t = 8 - 9 hrs.

    Malignant hyperthermia

    Inability to bind calcium by sarcoplasmic reticulum in some patients due to genetic defect . Sensitive to some drugs general anesthesia e.g. halothane neuromuscular blockers e.g. suxamethonium Ca release, intense muscle spasm, rise in Temp

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