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

Provide skeletal muscle relaxation to facilitate intubation of the trachea Provide optimal surgical working conditions 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: Its speed of onset Duration of action Rout of elimination 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

CAT Ca2+ AChE Ca2+ Ca2+ nAChR ACh ACh Acetate and choline ACh ACh Na+ High affinity choline carrier choline Na+ CAT AcCoA CoA choline ACh active transport 50% recaptured by nerve terminal ACh Empty vesicle ACh Acetate and choline ACh Ca2+ AChE ACh (8-10,000 molecules) ~100mM Na+ Ca2+ Voltage-dependent Ca2+ channels Na+ Ca2+ nAChR K+ Muscle fibre

Depolarizing (succinylcholine or Suxamethonium) Clinical use: - - - - - -

Averse effects 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 Sever liver disease Potent anticholine esterase (insecticides) Chemotherapy (cyclophosphamide) A typical pseudo cholinesterase

Nondepolarizing competitive

Factors enhance effects of NDMR Volatile anesthetics Aminoglycosides Antibiotics Mg Local analgesics Calcium channel blockers (verapamil) Cardiac antiarrythmias (quinidine) Hypothermia Acidosis Hypokalemia

Drug-assisted antagonism of Nondepolarizing muscle relaxants

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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