These<unk> s fall into two groups: *Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant<unk>  blockers. They act by competitively blocking the binding of ACh to its receptors, and in some cases, they also directly block the ionotropic activity of the ACh receptors. *Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber. This persistent depolarization makes the muscle fiber resistant to further stimulation by ACh. Non-depolarizing blocking agents A<unk>  non-depolarizing agent is a form of<unk>  blocker that 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<unk> s for muscle relaxation, most commonly in anesthesia. It is necessary to prevent spontaneous movement of muscle during surgical operations. Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. What they have in common, and is necessary for their effect, is the structural presence of quaternary ammonium groups, usually two. Some of them are found in nature and others are synthesized molecules. Mind Map showing a summary of<unk>  nondepolarizing agent Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing<unk>  blocker. It has a slow onset (>5 min) and a long duration of action (30 mins). Side-effects include hypotension, which is partially explained by its effect of increasing histamine release, a vasodilator, as well as its effect of blocking autonomic ganglia. It is excreted in the urine. This<unk>  needs to block about 70–80% of the ACh receptors for<unk>  conduction to fail, and hence for effective blockade to occur. At this stage, end-plate potentials (EPPs) can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction. +Comparison of non-depolarizing<unk>  blocking agents Agent Time to onset (seconds) Duration (minutes) Side effects Clinical use Storage Rapacuronium (Raplon) Bronchospasm Withdrawn due to Bronchospasm risk Mivacurium (Mivacron) 90 12–18 *hypotension (transiently), by release of histamine No longer manufactured secondary to marketing, manufacturing, and financial concerns refrigerated Atracurium (Tracrium) 90 30 min or less *hypotension, transiently, by release of histamine *Toxic metabolite called laudanosine, greater accumulation in individuals with renal failure widely refrigerated Doxacurium (Nuromax) long *hypotension, transiently, by release of histamine *Harmful metabolite called laudanosine (lowering seizure threshold); greater accumulation in individuals with renal failure Cisatracurium (Nimbex) 90 60–80 does not cause release of histamine refrigerated Vecuronium (Norcuron) 60 30–40 Few, may cause prolonged paralysis and promote muscarinic block widely non-refrigerated Rocuronium (Zemuron) 75 45–70 may promote muscarinic block non-refrigerated Pancuronium (Pavulon) 90 180 or more *tachycardia (slight) (no hypotension) widely non-refrigerated Tubocurarine (Jexin) 300 or more 60–120 *hypotension (by ganglion-block and histamine release) *Bronchoconstriction (by histamine release) rarely gallamine (Flaxedil) 300 or more 60–120 *tachycardia Pipecuronium 90 180 or more *tachycardia (slight) (no hypotension) non-refrigerated Depolarizing blocking agents A depolarizing<unk>  blocking agent is a form of<unk>  blocker that depolarizes the motor end plate. An example is succinylcholine. Mind Map showing a summary of<unk>  depolarizing agent Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine. However, these agents are more resistant to degradation by acetylcholinesterase, the enzyme responsible for degrading acetylcholine, and can thus more persistently depolarize the muscle fibers. This differs from acetylcholine, which is rapidly degraded and only transiently depolarizes the muscle. There are two phases to the depolarizing block. During phase I (depolarizing phase), they cause muscular fasciculations (muscle twitches) while they are depolarizing the muscle fibers. Eventually, after sufficient depolarization has occurred, phase II (desensitizing phase) sets in and the muscle is no longer responsive to acetylcholine released by the motoneurons. At this point, full<unk>  block has been achieved. The prototypical depolarizing blocking<unk>  is succinylcholine (suxamethonium). It is the only such<unk>  used clinically. It has a rapid onset (30 seconds) but very short duration of action (5–10 minutes) because of hydrolysis by various cholinesterases (such as butyrylcholinesterase in the blood). Succinylcholine was originally known as diacetylcholine because structurally it is composed of two acetylcholine molecules joined with a methyl group. Decamethonium is sometimes, but rarely, used in clinical practice. Comparison of<unk> s The main difference is in the reversal of these two types of<unk> s. * Non-depolarizing blockers are reversed by acetylcholinesterase inhibitor<unk> s since non-depolarizing blockers are competitive antagonists at the ACh receptor so can be reversed by increases in ACh. * The depolarizing blockers already have ACh-like actions, so these agents have prolonged effect under the influence of acetylcholinesterase inhibitors. Administration of depolarizing blockers initially produces fasciculations (a sudden twitch just before paralysis occurs). This is due to depolarization of the muscle. Also, post-operative pain is associated with depolarizing blockers. The tetanic fade is the failure of muscles to maintain a fused tetany at sufficiently high frequencies of electrical stimulation. * Non-depolarizing blockers have this effect on patients, probably by an effect on presynaptic receptors. * Depolarizing blockers do not cause the tetanic fade. However, a clinically similar manifestation called Phase II block occurs with repeated doses of suxamethonium. This discrepancy is diagnostically useful in case of intoxication of an unknown<unk> .
Neuromuscular-blocking drug
Neuromuscular blocking agents
Cholinergic blocking drugs
Antiprion drug
Antihypotensive agent
Muscle relaxant
Immunosuppressive drug
Antihypertensive drug