Drugs that increase or block transmission at the Neuromuscular Junction: 1.           Drugs that block release of Acetylcholi...

DRUGS THAT INCREASE OR BLOCK TRANSMISSION AT NEUROMUSCULAR JUNCTION |FINDYOURSELF

July 21, 2019 2 Comments

Drugs that increase or block transmission at the Neuromuscular Junction:

1.          Drugs that block release of Acetylcholine.

2.          E.g: Botulinum toxin, lack of Ca, excess of Mg.

3.          Botulinum prevents the release of Acetylcholine by blocking the fusion of Acetylcholine containing vesicles with the postsynaptic membrane & thus prevents the exocytosis of these vesicles. It has some therapeutic use to relieve pain of pathological contraction. 

4.          Lack of Calcium also leads to blocking of exocytosis of the secretory vesicles.

2. Drugs that stimulate the muscle fibre by Ach-like Action

•      Example: methacholine, carbachol, and nicotine

•      They have the same effect on the muscle fiber as does Ach. The difference b/w these drugs and Acetylcholine is that the drugs are NOT destroyed by cholinesterase or are destroyed so slowly that their action often persists for many minutes to several hours.

•      The drugs work by causing localized areas of depolarization of the muscle fiber membrane at the motor end plate where the acetylcholine receptors are located. Then, every time the muscle fiber recovers from a previous contraction, these depolarized areas, by virtue of leaking ions, initiate a new action potential. Thus, there is a constant state of muscle spasm.

3. Drugs That Stimulate the Neuromuscular Junction by
Inactivating Acetylcholinesterase.

•      Neostigmine, physostigmine, and diisopropyl fluorophosphate

•      They inactivate the acetylcholinesterase by combining with it in the synaptic cleft so that it no longer hydrolyzes acetylcholine. Therefore, with each successive nerve impulse, additional acetylcholine accumulates and stimulates the muscle fiber repetitively.

•      This causes muscle spasm when even a few nerve impulses reach the muscle. Unfortunately, it can also cause death due to laryngeal spasm, which smothers the person.

•      Neostigmine and physostigmine work for a few hours.

•      Diisopropyl fluorophosphate is effective for weeks. This makes it a particularly lethal poison with great military potential. It is thus used as a powerful “nerve gas poison”. 

4.          NON-DEPOLARIZING DRUGS:
Drugs That Block Transmission at the Neuromuscular Junction.

A group of drugs known as curariform drugs e.g. D-tubocurarine can prevent passage of impulses from the nerve ending into the muscle. This is done by competing with the Ach for the receptor sites on the postsynaptic membrane. When this drug is bound to these receptor sites, then Ach cannot act on them, thus preventing sufficient increase in permeability of the muscle membrane channels to initiate an action potential.

  It can have some therapeutic uses:

   - used with artificial respiration to control convulsions in tetanus.

   - used during surgery when complete muscle relaxation is required.