Download MUSCLE RELAXANTS

MUSCLE RELAXANTS
Muscle relaxants are drugs that
interrupt transmission of neural
impulses at the neuromuscular junction
History
Involved research using Banded Krait
(bungarotoxins) and cobra as well as
curare from South American plants
Banded Krait from Taiwan
Most potent source of curare
Clinical uses
1. Provide skeletal muscle relaxation to
facilitate intubation of the trachea
2. Provide optimal surgical working
conditions
3. In the intensive care setting to facilitate
mechanical ventilation of the lungs
Note
MR lack anesthetic or analgesic effects and
must not be used to render an
inadequately anesthetized patient
immobile
The choice of MR is influenced by:
1. Its speed of onset
2. Duration of action
3. Rout of elimination
4. Associated side effects
Neuromuscular junction
Consist of a prejuctional motor nerve ending
separated from the highly folded
postjunctional membrane by synaptic cleft
Neuromuscular transmission is initiated by
arrival of an impulse at the motor nerve
terminal with an associated influx of
calcium and a resultant release of
neurotransmitter acetylcholine
Ach binds to nicotinic cholinergic receptors
on postjunctional membrane, causing a
change in membrane permeability to ions,
principally K & Na ions
Ach is rapidly hydrolyzed by enz.
Acetylcholine esterase (true
cholinesterase)
Nicotinic cholinergic receptors
1.Prejunctional
2.Postjunctional
3.extrajunctional
Neuromuscular Junction
50% recaptured
by nerve terminal
ACh
ACh
Ca2+
Ca2+ Voltage-dependent
Ca2+ channels
Ca2+
Acetate and choline
ACh
ACh
(8-10,000
molecules)
~100mM
nAChR
Muscle fibre
Muscle relaxants
Depolarizing
noncompetitive
Nondepolarizing
competitive
Depolarizing (succinylcholine or
Suxamethonium)
Clinical use: - - - - - -
Averse effects
1.
2.
3.
4.
5.
6.
7.
8.
9.
Cardiac dysrthymia: Bradycardia, arrest
Myalgia
Myoglobinuria
Increased Intraocular pressure
Increased Intragastric pressure
Increased Intracranial pressure
Trismus
Allergic reactions
Trigger for malignant hyperthermia
10. Hyperkalemia
• Denervation injury (spinal cord
transection)
• Unhealed skeletal muscle injury as
produced by 3rd degree burn
• Upper motor neuron injury
• Multiple trauma
Causes of delayed recovery from
succinylcholine
1.
2.
3.
4.
Sever liver disease
Potent anticholine esterase (insecticides)
Chemotherapy (cyclophosphamide)
A typical pseudo cholinesterase
Nondepolarizing
competitive
Nondepolarizing
competitive
Long acting
(>30 min)
Pancuronium
D-tubocurarine
Gallamine
Intermediate acting
(15-25 min)
Vecuronium
Cis (atracurium)
rocuronuim
Short acting
(<15 min)
Mivacurium
Factors enhance effects of NDMR
1.
2.
3.
4.
5.
6.
7.
8.
9.
Volatile anesthetics
Aminoglycosides Antibiotics
Mg
Local analgesics
Calcium channel blockers (verapamil)
Cardiac antiarrythmias (quinidine)
Hypothermia
Acidosis
Hypokalemia
Drug-assisted antagonism of
Nondepolarizing muscle relaxants
Anti-choline
esterase
Neostigmine
edrophonium
pyridostigmine
Anticholinesterase
Drug accelerates the already established
pattern of spontaneous recovery at the
neuromuscular junction by inhibiting the
activity of acetylcholinesterase leading to
accumulation of ach. At nicotinic
(neuromuscular junction) and muscarinic
sites
The competition between ach and a
Nondepolarizing MR in favor of the
neurotransmitter (Ach) and restores
neuromuscular transmission
• Anticholinesterase does not cross blood
brain barrier
• Peripheral muscarinic effects block by
anticholinergic drugs like Atropine
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