Nervous system signalling context
The nervous signalling to skeletal muscle occurs through nicotinic receptors which use acetylcholine. These are quick receptors, which acetylcholine binds to them they let in Na+ ions, leading to action potentials with enough sodium at the neuromuscular junction
Additionally different tissues have different isoforms of the nicotinic receptors and therefore different characteristics
If we want to stop the effects of acetylcholine on the muscles we can do this by:
- Inhibiting release of ACh
- Inhibiting esterase which breaks down ACh (causing tetanus)
- Inhibiting nicotinic receptors at the NMJ
This brings us to the drugs:
The drugs
We can have depolarising and nondepolarising blockers. Nondepolarising blockers are competitive agonists which compete at the NMJ with ACh and with enough concentration ACh will have no effect as it cannot get through. Depolarising on the other hand is depolarising and giving it leads to brief tetanus, then a mandatory inability for action potential to take place. The happens because after the tetanus the myocytes think there is something wrong with the acetylcholine receptors and take them all into the cell to replace them. This means once it is administered you cannot do anything about it until the receptors are replaced,
Non-depolarising
Rocuronium tubocuranine (competitive antagonist) also reversable as it is competitive (slow but fast to clear) not absorbed orally quaternary ammonium compound
a lot of ACh gets release and so only
add neostigimine which is a ACh esterase inhibitor to functionally magnify ACh
Depolarising
suxamethoium decomethonium (agonist) (fast but long to clear)
overactivates nicotinic receptors.
phase 1 block causes tetanic spasms and then flaccidity as loss of membrane potential decmethonium can be metabolised out
phase 2 block this is bc muscles figure out receptors are damaged and endocytoses receptors so then you have to wait for new receptors