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 3. Provide optimal surgical working conditions 5. 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 3. Duration of action 5. Rout of elimination 7. 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

High affinity choline carrier

AcCoA CoA

choline

choline Na+

CAT

ACh active transport
Empty vesicle

50% recaptured by nerve terminal

ACh ACh ACh

Acetate and choline

Ca2+
Ca
2+

AChE
(8-10,000 molecules) ~100mM

Voltage-dependent Ca2+ channels

ACh

Na+

Na+ K+

Ca2+

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 (min 30>) Pancuronium D-tubocurarine Gallamine

Intermediate acting (min 15-25) Vecuronium (Cis (atracurium rocuronuim

Short acting (min 15<) 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

Thank you