Transcript Lecture 2- skeletal muscle relaxants.ppt

Skeletal muscle relaxants
Prof. Hanan Hagar
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
Neuromuscular blockers
Classification:
1) Competitive (non depolarizing blockers)
2) Depolarizing blockers
Neuromuscular Junction
Uses of neuromuscular blockers
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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.

Competitive (Nondepolarizing) muscle
relaxants
◦ Short acting
◦ Intermediate acting
◦ Long acting

Depolarizing muscle relaxant
◦ Succinylcholine

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
hypotension
o 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
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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)
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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).
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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)

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.
2.
3.
4.
SK. muscle : initial contraction followed by
relaxation.
Hyperkalemia : Cardiac arrest.
Eye :  intraocular pressure.
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
Notes
Tubocurarine
Long
1-2 h
Hypotension
# Renal failure
Pancuronium
Long
1-2 h
Tachycardia
# Renal failure
Transient
hypotension
Histamine release
Spontaneous
degradation
Used in liver and
kidney failure
Few side effects
# Liver failure
Atracurium
Short
30 min.
Vecuronium
Short
40 min.
Mivacurium
Short
15 min.
Succinyl
choline
Short
10 min.
Similar to
atracurium
Hyperkalemia
Arrhythmia
Increase IOP
Metabolized by
pseudocholinesterase
# Choline esterase
deficiency
# CVS Diseases
# Glaucoma
# Liver disease
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.
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