NEUROMUSCULAR JUNCTION BLOCKERS

BY :DR ISRAA OMAR

Muscle Relaxants (Neuromuscular blocking drugs)

• Neuromuscular blocking drugs block cholinergic transmission between motor nerve endings & the nicotinic receptors on the neuromuscular end plate of skeletal muscle.

Neuromuscular Junction (NMJ)

Binding of Ach to receptors on muscle end-plate

Muscle Relaxants

1. Depolarizing muscle relaxant – Succinylcholine

2. Nondepolarizing muscle relaxants– Short acting– Intermediate acting– Long acting

1. Depolarizing Muscle Relaxant• SuccinylcholineMechanism of action: – Physically resemble Acetylcholine– Act as acetylcholine receptor agonist– Not metabolized locally at NMJ–Metabolized by pseudocholinesterase in plasma– Depolarizing action persists > Acetylcholine– Continuous end-plate depolarization causes

muscle relaxation

Depolarizing Muscle Relaxant• Clinical use: –Most often used to facilitate intubation– Electroconvulsive therapy

• Side effects: – Fasciculation–Muscle pain–Hyperkalemia –Malignant hyperthermia–Apnea

2. Non depolarizing Muscle Relaxants (Competitive blockers)• Mechanism of action: – Compete with Acetylcholine at the binding sites– Do not depolarized the motor endplate– Act as competitive antagonist– Excessive concentration causing channel blockade– Act at presynaptic sites, prevent movement of

Acetylcholine to release sites

Nondepolarizing Muscle Relaxants

A. Long acting–Pancuronium

B. Intermediate acting–Atracurium

C. Short acting–Mivacurium

Myasthenia gravis

• This is an autoimmune disease manifested by muscle weakness and increased fatigability resulting from failure of neuromuscular transmission .

• The release of ACh from nerve terminal is normal but the nicotinic receptors are reduced by antibodies circulating in the plasma

• This disease is treated by cholinesterase inhibitors like Physostigmine which greatly increase the muscle function and corticosteroids which reduce the immunological attack

• Eaton –Lampart syndrome is variant of myasthenia associated with internal malignancy

Myasthenia gravis

Drugs affecting autonomic ganglia

Ganglion stimulating agents

• Nicotine, lobeline, and dimethylphenylpiprazinum (DMMP).

• They stimulate autonomic ganglia preferentially• Only nicotine is used clinically to help people for

stop smoking; other wise they are used as experimental tools

• They cause complex peripheral effect associated with generalized stimulation of the autonomic ganglia

Effects of ganglionic blocking agents

• Effects are complex but those for CVS and the visceral smooth muscles are the most important.

• In the CVS there is a fall in arterial blood pressure and cardiac output; postural hypotension; post exercise hypotension .

• In motility of all part of the GIT and urinary tract is inhibited and this leads to constipation, urine retention and sexual dysfunction.

Mechanism of action1. Inhibition of acetylcholine release – Botulinum toxin, hemicholinium, magnesium ion

2. Non- depolarizing blockers: – Hexamethonium, mecamylamine and trimethaphan – Used historically for treatment of hypertension.

3. Depolarization block: – Occurs when the receptors is persistently

depolarized by nicotinic agonist (nicotine) and results in decrease electrical excitability of post-synaptic cells

Good luck

Reference• Rang and Dale pharmacology