Skeletal muscle relaxants

Prof. Hanan Hagar

Skeletal muscle relaxantsAre 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

Neuromuscular blockers

Classification:

1) Competitive (non depolarizing blockers) 2) Depolarizing blockers

Binding of Ach to receptors on muscle end-plate

Neuromuscular Junction

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.

Muscle Relaxants

Competitive (Nondepolarizing) muscle relaxants◦Short acting◦Intermediate acting◦Long acting

Depolarizing muscle relaxant ◦Succinylcholine

Competitive NM blockers Long acting◦d-tubocurarine◦Pancuronium

Intermediate acting◦Atracurium◦Cisatracurium◦Vecuronium◦Rocuronium

Short acting◦Mivacurium

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

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)

Pharmacological actions:

Skeletal muscle relaxation. They produce different effects on CVS Some release histamine and produce

hypotensiono d.Tubocurarine o Atracurium o Mivacurium

Others produce tachycardia ( H.R)o Pancuronium

d – Tubocurarine

Long duration of action (1 - 2 hr) Eliminated by kidney 60% - liver 40%. Releases histamine that causes:

◦Bronchospasm

◦Hypotension

◦Tachycardia

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)

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).

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)

Vecuronium More potent than tubocurarine ( 6 times ).Metabolized mainly by liver.Intermediate duration of action.Has few side effects.

◦No histamine release.

◦No tachycardia.

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

Succinylcholine (suxamethonium)

Pharmacological Actions

1. SK. muscle : initial contraction followed by

relaxation.

2. Hyperkalemia : Cardiac arrest.

3. Eye : intraocular pressure.

4. CVS : arrhythmia

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).

Side Effects Hyperkalemia CVS arrhythmia IOP # glaucoma Can produce malignant hyperthermia May cause succinylcholine apnea due to

deficiency of pseudocholinesterase.

Drug Duration Side effects NotesTubocurarine Long

1-2 hHypotension # Renal failure

Pancuronium Long1-2 h

Tachycardia # Renal failure

Atracurium Short30 min.

Transient hypotension

Histamine release

Spontaneous degradation

Used in liver and kidney failure

Vecuronium Short 40 min.

Few side effects # Liver failure

Mivacurium Short 15 min.

Similar to atracurium

Metabolized by pseudocholinesterase# Choline esterase

deficiency

Succinyl choline

Short10 min.

HyperkalemiaArrhythmiaIncrease IOP

# CVS Diseases# Glaucoma

# Liver disease

Alteration of responses

Diseases ◦Myasthenia gravis◦Kidney failure◦Liver failure

Drug interactions◦Inhalation & Intravenous anesthetics◦Aminoglycosides antibiotics ◦Anticonvulsants◦Magnesium

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

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

Uses of spasmolytics They reduce muscle spasm in spastic states

produced by :

Spinal cord injury Cerebral stroke Cerebral palsy

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.