1. NEUROMUSCULAR JUNCTION BLOCKERS
BY :DR ISRAA OMAR

2. 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.

3. Neuromuscular Junction (NMJ)

4. Binding of Ach to receptors on muscle end-plate

5. Muscle Relaxants Depolarizing muscle relaxant
Succinylcholine
Nondepolarizing muscle relaxants
Short acting
Intermediate acting
Long acting

6. 1. Depolarizing Muscle Relaxant
Succinylcholine
Mechanism 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

7. Depolarizing Muscle Relaxant
Clinical use:
Most often used to facilitate intubation
Electroconvulsive therapy
Side effects:
Fasciculation
Muscle pain
Hyperkalemia
Malignant hyperthermia
Apnea

8. 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

9. Nondepolarizing Muscle Relaxants
Long acting
Pancuronium
Intermediate acting
Atracurium
Short acting
Mivacurium

10. 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

11. Myasthenia gravis
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

12. Drugs affecting autonomic ganglia

13. 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

14. Ganglionic blocking agents
Mechanism of action
Inhibition of acetylcholine release
Botulinum toxin, hemicholinium, magnesium ion
Non- depolarizing blockers:
Hexamethonium, mecamylamine and trimethaphan
Used historically for treatment of hypertension.
Depolarization block:
Occurs when the receptors is persistently depolarized by nicotinic agonist (nicotine) and results in decrease electrical excitability of post-synaptic cells

15. 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.

16. Good luck

17. Reference
Rang and Dale pharmacology