Skeletal Muscle Relaxant - Majmaah University

Skeletal Muscle Relaxant - Majmaah University

Skeletal Muscle Relaxants Dr Naser Ashraf Types of skeletal muscle relaxants: 2 groups Neuromuscular blockers Relax normal muscles (surgery and assistance of ventilation) No central nervous system activity. Used primarily as a part of general anesthesia Spasmolytics Reduce spasticity Centrally acting (except dantrolene which act on the skeletal muscle) Used in a variety of neurologic conditions

Skeletal Muscle Relaxants Neuromuscular blockers Spasmolytics Non-depolarizing (Competitive) D tubocurarine Pancuronium Vecuronium Atracurium Mivacurium Depolarizing (Non-Competitive) Succinylcholine Decamethomium

Directly acting Centrally acting Diazepam Chlorzoxazone Tizanidine Baclofen

Dantrolene Skeletal Muscle contraction Na+ Na + ab 2+ a Ca ACH ote

nti al ACH ACH NMreceptor b a Motor neuron ACH ACH ACH ACH ACH ACH

a Ac tio nP ACH ACH ACH ACH a ba Skeletal Muscle ACHEsterase Mechanism of action of

Neuromuscular Blockers Normal d-Tubocurarine A Ch Ach Ach Ach SCh SCh Ach Depolarization

Succinylcholine No Depolarization Repolarization Contraction No contraction Relaxation Flaccid Paralysis Persistent Depolarization Contraction (Fasciculation) Relaxation Competitive Antagonists

(Non-depolarizing Blockers) (Non-depolarizing blockers) Long-acting: d tubocurarine, pancuronium Intermediate: Atracurium , vecuronium , rocuronium , Anti-cholinestrases (neostigmine, edrophonium) which preserve acetylcholine are used to reverse

the effect of d-tubocurarine Mechanism of Action Competitive Antagonism Agonist Ach Ach Antagonist d-Tubocurarine Affinity : Yes Intrinsic action : No NM receptor Motor End Plate Actions

Muscle weakness Flaccid paralysis Order of muscle affected: Extrinsic eye muscles, muscles of finger Neck muscles (muscles of phonation and swallowing) Face Hands, Feet Trunk Respiratory muscles (intercostal and diaphragm) Recovery in the reverse order Consciousness, appreciation of pain not affected

Actions Autonomic ganglion blocking property Histamine release (by d-tubocurarine) CVS Significant fall in BP Increase in Heart rate Vagal gangionic blockade (also ve and pan) Newer competitive blockers: Negligible effect on BP and HR Adverse effects Hypotension

Tachycardia Respiratory paralysis Bronchospasm Aspiration of gastric contents Advantages of synthetic (Newer) competitive blockers Less histamine release Do not block autonomic ganglia Spontaneous recovery with most of drugs Rapacuronium & rocuronium have rapid onset Atracuronium: Hoffmans elimination Mivacurium short acting

Uses As an adjunct to general anaesthesia For producing satisfactory skeletal muscle relaxation For facilitating endotracheal intubation Rocuronium preferred due to rapid onset of action Succinylcholine is better due to short lasting duration Depolarizing Blocker (Non-competitive Antagonist) Succinylcholine One Drug, Two blocks, Brief and quick, Genetic variability in metabolism, Malignant hyperthermia

Skeletal Muscle Relaxants Quaternary ammonium Succinyl Choline Depolarising muscle relaxants Two molecules of Acetylcholine) Acetylcholine Quaternary ammonium Mechanism of action Agonist at Nicotinic (NM) receptor Produces neuromuscular block by overstimulation, end plate is unable to respond to further stimulation.

Longer lasting or persistent depolarization Succinylcholine Actions Small rapidly moving muscles (eye, jaw, larynx) relax before those of limbs and trunks Ultimately intercostals and finally diaphragm paralysis occur respiratory paralysis Recovery in the reverse order Muscle relaxation: Onset: within 1 min; peak: 2 min, duration: 5 min; longer duration relaxation requires continued IV infusion Succinylcholine Uses Suitable for short-term procedures Rapid endotracheal intubation during induction of anaesthesia

During Electro-Convulsive shock Therapy (ECT) To prevent injury Succinylcholine Adverse Effects Transient Intraocular Tension Hyperkalemia : Fasciculations release potassium in blood Succinylcholine apnoea Malignant hyperthermia: when used alng with halothane in general anaesthesia Treatment is by rapid cooling of patient & dantrolene i.v Muscle pain Treatment of succinylcholine apnoea No antidote is available

Fresh frozen plasma should be infused Patient should be ventilated artificially untill full recovery Comparison of Competitive and Depolarizing Blocking Agents Sr.no 1 2 3 4 Competitive Competitive blockade Non depolarizing Single block Anticholinesterases reverse blockade Succinyl choline

Persistant depolarization Depolarizing Dual block Do not reverse 5 Initial fasciculations not Present present 6 Slow onset long duration Rapid onset short duration 7

Release histamine Doesnt release Dantrolene Directly acting skeletal Muscle relaxant Inhibits depolarization induced calcium release from sarcoplasmic reticulum by acting on ryanodine receptors Drug of choice in malignant hyperthermia Drug interactions Non depolarizing blockers Anticholine-esterases (Neostigmine) Reverse the action of only non depolarizing blockers Halothane, Aminoglycoside antibiotic like gentamicin & calcium channel blockers like nifedipine

Enhances the neuromuscular blockade Depolarizing blockers Halothane can cause malignant hyperthermia Ganglion blockers Competitive blockers Persistant depolarizing Hexamethonium Trimethaphan Mecamylamine Nicotine large dose Actions & Adverse effects of ganglion blockers S.No Organ

Dominant ANS Effect/(side effect)of ganglionic blockade 1. Heart Parasympathetic Tachycardia (Palpitations) 2. Blood vessels Sympathetic

Vasodilation (Hypotension) 3. Iris Parasympathetic Mydriasis (Photophobia) 4. Ciliary Muscle Parasympathetic Cycloplegia (Blurring of vision) 5.

Intestines Parasympathetic motility (Constipation) 6. Bladder Parasympathetic tone (difficulty in micturation) 7. Male sexual function Parasympathetic Inhibition of erection & ejaculation (Impotence)

8. Salivary Glands Parasympathetic Inhibition of salivation (dry mouth, difficulty in swallowing) 9. Sweat Glands Sympathetic Inhibition of sweating

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