DEPOLARIZINGNEUROMUSCULAR BLOCKERS Prepared by: Dr. Sara Khalid Memon 3rd year, MBBS
Background :Generally, when an impulse reaches to the muscle, itcauses it to contract when it is excited. This occursin various stages and the main player in this wholesequence is the NEUROTRANSMITTER that isreleased from the nerve ending onto the motor endplate !This neurotransmitter works when binds to thereceptors on the motor end plate. If it binds andcauses intrinsic activity of the receptor then itwould b called as Agonist , and if a substance justbinds to receptors without causing intrinsic activitythen it is said to b Antagonist.
1. Axon2. Motor end plate3. Muscle Fiber4. Myofibril
Receptor blockers can be depolarizing or Nondepolarizing depending upon the activity theycause in the motor end plate (muscle).Blockers are said to be non depolarizing when theydo not elicit any action potential or any activity inthe effector and block the action of endogenousligand by just binding to the receptors. On theother hand, Depolarizing blockers are those whichdo elicit the action potentials in the effector butmake effector site desensitized and henceendogenous ligand (epinephrine and norepinephrinehere) is unable to produce response.
Depolarizing Neuromuscular Blockersinclude:>> Succinyl-Choline>> DecamethoniumNote: These are not the antagonists in actualsense, infact there action is ofagonist, therefore acetylcholine itselfpharmacologically be used as a depolarizing NMB!
Succinylcholine:>Other names: Suxamethonium Chloride(suxamthonium).-Sold under trade names: Anectine, Quelicine, Scoline>Works on the nicotinic receptors (as acetylcholinedoes)> Onset of action is very rapid (within few seconds)and its duration of action doesn’t last for more thenfew minutes.> Degraded by pseudocholine esterase(butyrylcholine esterase in plasma) intosuccinylmonocholine and choline and is excreted inUrine.
Mechanism Of Action:Succinylcholine acts on the nicotinic receptors of themuscles, stimulates them and then ultimately causetheir relaxation.> This process occurs in 2 steps;> Phase I: During phase I (depolarizing phase), theycause muscular fasciculations (muscle twitches) whilethey are depolarizing the muscle fibers.> Phase II: After sufficient depolarization hasoccurred, phase II (desensitizing phase) sets in andthe muscle is no longer responsive to acetylcholinereleased by the nerve endings.
Explanation:> In normal skeletal muscle, acetylcholine dissociatesfrom the receptor following depolarization and israpidly hydrolyzed by acetylcholinesterase.> Suxamethonium has a longer duration of effect thanacetylcholine, and is not hydrolyzed byacetylcholinesterase. By maintaining the membranepotential above threshold, it does not allow the musclecell to repolarize. When acetylcholine binds to analready depolarized receptor, it cannot cause furtherdepolarization.>This later leads to Paralysis of the affected muscles!!!!
Sequence of paralysis:Short muscles are paralysed first then later occursparalysis of other muscles which may lead to death.Finger and orbit muscles Limbs and trunkmuscles Neck muscles Intercostals DIAPHRAGMNOTE:Recovery from paralysis occurs in reverse sequence!
Uses of depolarizing neuromuscular blockers(succinylcholine):> For Endotracheal intubation.> during electro convulsive therapy.> For laryngoscopy, bronchoscopy, esophagoscopy> For correction of dislocation and alignment offractures> As a Muscle relaxant !
Adverse Effects:> Hyperkalemia> Malignant Hyperthermia> Increased intraocular pressure> Increased cranial pressure> changes in cardiac rhythm, includingbradycardia, cardiac arrest and ventriculardysrhythmias.> For causing death =P