This document discusses neuromuscular blockers, which are drugs that block transmission between motor neurons and muscles. It describes two main types - non-depolarizing and depolarizing. Non-depolarizing blockers like pancuronium competitively block acetylcholine receptors without depolarizing the muscle. Depolarizing blockers like succinylcholine initially cause muscle contraction but then induce prolonged depolarization, preventing further signaling. The document provides examples of long, intermediate, and short acting non-depolarizing drugs and explains their mechanisms of action and uses, particularly in anesthesia and surgery to induce muscle relaxation.
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Acetylcholine is an organic chemical that functions in the brain and body of many types of animals as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells, such as neurons, muscle cells and gland cells.
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pharmacology,clinical pharmacology,clinical,injections,pharmacological,what is pharmacology,lethal injection drugs,pharmacology definition,Plus review of anatomy of the ANS
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2. Definition:
Also known as skeletal muscle relaxants.
These are those agents in drugs which are used to block the
cholinergic transmission between motor nerve ending and
nicotinic receptor on the neuromuscular end plate of skeletal
muscle.
Neuromuscular junction: junction between neuron and
muscles in which Neurotransmitters release from neuron and
bind with receptors present on muscles and cause contraction
and movement.
5. Non-depolarizing blockers:
These drugs does not depolarize the motor end plate.
The quaternary ammonium muscle relaxants belong to this class.
Quaternary ammonium muscle relaxants are quaternary ammonium salts
used as drugs for muscle relaxation most commonly used in anesthesia. It
is necessary to prevent spontaneous movement of muscle during surgical
operations.
Which are poorly absorbed and rapidly excreted and can't cross placenta.
They inhibit neuron transmission to muscle by competitively blocking the
binding of acetylcholine(Ach) to its nicotinic receptors and block the
ionotropic activity of the Ach receptors.
6. Non-depolarizing drugs:
Long acting:
i. Pancuronium
Intermediate acting:
I. Atracurium
II. Vercuronium
III. Rocuronium
IV. Cisatracurium
Short Acting:
I. Mivacurium
7. Depolarizing Blockers:
An example is Succinylcholine.
The most commonly used depolarizing blocker is succinylcholine (also
called suxamethonium or SCh). When administered intravenously,
succinylcholine rapidly binds to the nicotinic acetylcholine receptors on
the motor endplate of skeletal muscles. It causes a brief initial
depolarization, which leads to muscle fasciculation or twitches.
However, succinylcholine's unique characteristic is that it is metabolized
more slowly than acetylcholine.
8. Succinylcholine:
Dose required for Tracheal intubation in adults is 1.0-1.5 mg kg.
This dose produces profound block within 60sec.
But very short duration of action about 5-10 minutes because of Plasma
cholinesterase, which has an enormous capacity to hydrolyze
succinylcholine.
10. Mechanism of Action(Non-Depolarizing):
The competitive blocker have affinity for the nicotinic cholinergic
receptor at the muscle end plate, but have no intrinsic activity.
The two α-subunit carry two acetylcholine(Ach) binding sites in
Nicotinic receptor.
Most of the competitive blockers attract for the same site, but due to
bulky nature of competitive blockers molecules does not allow
conformational changes in subunits for opening of channel.
11. Acetylcholine (Ach) molecule released fro motor nerve ending
are not able to combine with the receptor of end plate
potential.
There fore muscle fails to contract.
13. Mechanism of Action(Depolarizing):
The depolarizing agent such as succinylcholine act by
different mechanism.
Their initial cation is to depolarize the membrane by opening
channels in the same manner as acetylcholine.
But the depolarizing is for longer time because
acetylcholine(ach) is destroyed by cholinesterase.
14. Longer lasting depolarization make receptor incapable for
further signaling.
Therefore muscle fails to contract. These drugs produce rapid
complete paralysis and the recovery is spontaneous.
16. Uses:
Acute muscle spasms: The mephenesin-like and BZD muscle relaxants,
combined with analgesics.
Torticollis (tilted and twisted neck),lumbago (pain in the muscle and
joints of the lower back), back ache, neuralgias (pain caused by
damaged nerves)
Anxiety and tension: Diazepam group
Spastic neurological diseases: These conditions are benefited by
baclofen, diazepam, tizanidine and dantrolene.
Tetanus: Diazepam, methocarbamol
Electroconvulsive therapy: Diazepam
Orthopedic manipulations: Diazepam, methocarbamol