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Similar to Sk. Muscle Relaxantsnursing and its side effects
Sk. Muscle Relaxantsnursing and its side effects
- 4. Upper motor neuronfrom cerebral cortex activated AP travels in the neuron AP travels to spinal cord,release of epinephrine,glutamate AP excites lower motor neuron Muscle contraction
- 7. Arrival of anaction potential at the motor nerve terminal Influx of calcium Release of acetylcholine Diffusion of acetylcholine across the synaptic cleft Activation of nicotinic receptors on motor end plate
- 8. Ach Nicotinic Receptor (PENTAMER) 2α,1β, 1γ, 1δ
- 9. Binding of twoacetylcholine molecules to receptors on the α-β and δ-α subunits Opening of the channel Movement of sodium & potassium through the channel A graded depolarization of the end plate membrane - motor end plate potential Adjacent muscle membrane is depolarized, and an action potential propagated along the entire muscle fiber
- 10. Muscle contraction is theninitiated by excitation- contraction coupling Released acetylcholine is quickly removed from the end plate region AP depolarizes muscle membrane + travels deeply within the muscle fiber SR release Ca++ Ca++ initiates attractive forces between Actin & Myosin filaments Ca++ pumped back into SR Diffusion & enzymatic destruction by the local acetylcholinesterase enzyme
- 11. By interruption offunction at several sites Along the pathway from the central nervous system (CNS) to myelinated somatic nerves Unmyelinated motor nerve terminals Nicotinic acetylcholine receptors Motor end plate Muscle membrane Intracellular muscular contractile apparatus
- 12. CENTRALLY ACTING Spasmolytics DIRECTLY ACTING Dantrolene PERIPHERALLY ACTING Neuromuscular Blockers Depolarizing Non-depolarizing
- 13. Spasmolytics Diazepam Baclofen Tizanidine Gabapentin Progabide Glycine Idrocilamide, riluzole (for ALS)
- 14. I- STIMULANTS Choline esters Anticholinesterases II-BLOCKERS A. Non-Depolarizing D-tubocurarine Gallamine Pancuronium Atracurium Cisatracurium Mivacurium B. Depolarizing Succinylcholine (Suxamethoniu m) Suxethonium Decamethonium
- 16. Prevent or interruptmuscle spasm associated with: Spastic diseases Spinal cord injury Overexertion of muscles Adjunct treatment for: Anesthesia Intubation surgical& orthopedic procedures
- 17. Facilitates GABA(inhibitory) transmission in the CNS Diazepam although acts more through GABAA but through GABAB spasmolytic effect is more pronounced Muscle relaxant activity is due to inhibition of polysynaptic pathways in spinal cord Sedation Centrally Acting Muscle Relaxants
- 20. Orally effectiveGABA-mimetic agent GABA agonist at GABAB receptors MECHANISM OF ACTION: Hyperpolarization Decrease the release of excitatory transmitters in both the brain & SC Reduce pain in pts with spasticity (inhibiting the release of substance P in SC) It is as effective as Diazepam having advantage causes less sedation Baclofen (contd.)
- 21. Increases K+conductance - hyperpolarization of neuronal membrane Decreases Ca++ influx Less sedation & muscular weakness Can be given intrathecally in severe spasms Alcoholics to reduce craving Centrally Acting Muscle Relaxants
- 23. ADVERSE EFFECTS: CNSdepression Confusion Delirium Coma Impaired renal function
- 24. Congener ofclonidine α2 agonist Reinforces both pre & postsynaptic inhibition in spinal cord ADVERSE EFFECTS 1. Hypotension 2. Asthenia 3. Sedation 4. CNS depression Centrally Acting Muscle Relaxants
- 26. Blocking the effect ofphysiological agonist Excess of depolarizing agonist Tubocurarine Acetylcholine Succinylcholine Non-depolarizing blockade Depolarizing blockade
- 29. Curare -arrow poison Strychnos species Strychnos toxifera Quarternary neuromuscular - blocking alkaloids
- 30. Structural resemblance to acetylcholine Succinylcholine:2acetylcholine molecules linked end-to-end Presence of one or two quaternary nitrogens - makes them poorly lipid soluble and limits entry into the CNS
- 31. BENZYL- ISOQUINOLINES Natural d-Tubocurarine Synthetic Mivacurium* Atracurium* Doxacurium Gantacurium AMMONIO- STEROIDS Rapacuronium Rocuronium* Vecuronium* Pancuronium* Pipecuronium 31 Mixed-onium chlorofumarates Gantacurium
- 32. Ultra shortacting: Succinylcholine (Dep) Gantacurium (investigational) Short acting: Mivacurium slow onset Intermediate acting: Vecuronium hepatic& billiary exc. Rocuronium fastest onset atracurium Hofman elimination cisatracurium,
- 33. Long acting: D-Tubocurarine*(prototype) metocurine pancuronium* doxacurium
- 34. Prototype: d, tubocurarine Mono-quarternaryammonium alkaloid Highly polar Not absorbed from GUT NOT metabolised in liver Excreted unchanged
- 35. Atracurium -intermediate-acting Hepatic metabolism + Hofmann elimination Breakdown products laudanosine - slowly metabolized by the liver - longer elimination half-life (ie, 150 minutes) - readily crosses BBB - high blood concentrations: seizures Cisatracurium
- 36. Site ofaction: motor end plate Competes with acetylcholine for nicotinic receptors Blockade is competitive and surmountable Decrease frequency of channel opening Not preceded by fasciculation
- 38. Action canbe reversed by neostigmine, edrophonium An important clinical consequence:* reversal of residual blockade by cholinesterase inhibitors
- 39. Succinylcholine: Extremelyshort duration of action(5–10 minutes) Rapid hydrolysis by butyrylcholinesterase (liver) & predominantly pseudocholinesterase (plasma) Circulating levels of plasma cholinesterase influence the duration of action of succinylcholine DIBUCAINE NUMBER
- 41. Phase-I block (Depolarizing) Mimics action of acetylcholine at motor end plate Binds to nicotinic ion channels and opens Depolarization of motor end plate – spreads to adjacent membranes causing contractions of motor units Succinylcholine not metabolized as effectively as acetylcholine at synapse – depolarized membrane remains depolarized & unresponsive to subsequent impulses
- 43. Phase-I block (Depolarizing) End plate repolarization “repriming” required for excitation-contraction coupling and repetitive firing to maintain muscle tension Flaccid paralysis results which is preceded by fasciculation Phase-I block is augmented but not reversed by anticholinesterases
- 44. Phase II Block(Desensitizing) Persistent depolarization slowly decreases- repolarization starts – can not be depolarized…..desensitization of the membrane Cause: Channel block . channel behaves like in a prolonged closed state - Later in phase II: behaves like block by non-depolarizing drugs and can be reversed by anticholinesterases
- 45. Motor muscleweakness total flaccid paralysis Muscles capable of rapid movement (eye, jaw, larynx )…….. paralyzed first Then neck, limbs, trunk…… paralyzed Diaphragm and other respiratory muscles……. last to be paralyzed Recovery occurs in reverse order i.e diaphragm to be the first to recover and facial muscles are last of all
- 46. Bronchospasm(histamine release) Raised intraocular pressure(succinylcholine) Increased intra-gastric pressure (increased risk of regurgitation & aspiration of stomach contents) Myalgias (succinylcholine) HYPERKALEMIA
- 47. PROLONGED APNEA Airwayobstruction Neuromuscular depressant effect of excessive neostigmine Low plasma butyrylcholinesterase Presence of latent myasthenia gravis Decreased elimination: hepatic dysfunction (cisatracurium, rocuronium, vecuronium) or renal dysfunction (pancuronium)
- 48. MOA: Interferes withthe release of calcium from its stores in the sarcoplasmic reticulum of the sarcomere & thus reduces the muscle strength by affecting excitation-contraction coupling in the muscle fibre Calcium exits out of sarcoplasmic reticulum through Ryanodine channels Dantrolene probably combines with the same channel and interferes with the release of the Ca++ Cardiac &smooth muscles are depressed slightly
- 50. CLINICAL USES Malignant hyperthermia ADVERSEEFFECTS Sedation Muscular weakness Fatigue Rashes Jaundice/hepatitis Diarrhea Should be used with caution in concomitant hepatic, renal ,cardiac and pulmonary disorders.
- 51. Chemodenervation & localparalysis in muscle Cosmetic Cerebral palsy Dystonia Overactive bladder incontinence Chronic migraine
- 52. Cyclobenzaprine* (prototype), antimuscariniceffects – sedation, transient visual hallucinations Carisoprodol Chlorphenesin* Chlorzoxazone Metaxalone Methocarbamol Orphenadrine*
- 53. Succinylcholine, halothane Life threatening condition Contracture, rigidity & heat production from skeletal muscle -hyperthermia, metabolic acidosis, tachycardia Uncontrolled release of Ca+2 from SR (Ryanodine receptor) Genetic predisposition Dantrolene, rapid cooling 100% oxygen, control of acidosis
- 55. Skeletal musclerelaxant during surgery Orthopedic manipulations Facilitate endotracheal intubation Facilitate laryngoscopy, bronchoscopy, esophagoscopy Tetanic convulsions & Status epilepticus In Modified ECT As a treatment of crush injures of chest Rx of poisoning due to convulsant drugs e.g. strychnine
- 56. Myasthenia gravis Concomitant use of aminoglycosides Asthmatic patients Hypotensive states Succinylcholine in children Hyperkalemia (caution with other conditions/drugs) Severe liver/kidney disease Atypical pseudocholinesterase in patients
- 57.
- 58. d-Tubocurarine Suxamethonium Source: NaturalSynthetic Chemistry Alkaloid, Monoquaternary Ammonium Compound Two molecules of acetylcholine joined together Mechanism of action Non-depolarizing; competitive antagonism with ACH at nicotinic receptors of motor end plate Persistent depolarizing (action like ACH) followedby desensitization of area around motor end plate. Initial fasciculations Absent Present
- 59. d-Tubocurarine Suxamethonium Onset ofaction 4 minutes 1 minute Duration of action 20-30 minutes 4-10 minutes Effect on histamine release Moderate Slight Metabolism Not metabolised Rapidly hydrolysed by pseudocholinesterase. Excretion Mainly through kidney as unchanged Only a small proportion is excreted unchanged Effect of administration of neostigmine Antagonistic Augmented during Phase I; Antagonistic during Phase II
- 60. d-Tubocurarine Suxamethonium Effect of administration oftubocurarine Antagonistic during Phase I; Augmented during Phase II Pharmacogeneti cs No genetic problem Prolonged apnea due to atypical pseudocholinesterase Main Uses As adjuvant to anesthesia for moderate to prolonged operations For rapid endotracheal intubation for operations of short duration
- 61. Non depolarizing blockade: Cholinesterase inhibitors Neostigmine Pyridostigmine Edrophonium Suggammadex(for rocuronium) Depolarizing blockade Phase1:cannot be reversed Phase2: same as non depolarizing blockade
- 62.
Editor's Notes
- #10 The magnitude of the end plate potential is directly related to the amount of acetylcholine released. If the potential is small, the permeability and the end plate potential return to normal without an impulse being propagated from the end plate region to the rest of the muscle membrane. At least two additional types of acetylcholine receptors are found within the neuromuscular apparatus. One type is located on the presynaptic motor axon terminal, and activation of these receptors mobilizes additional transmitter for subsequent release by moving more acetylcholine vesicles toward the synaptic mem-brane. The second type of receptor is found on perijunctional cells and is not normally involved in neuromuscular transmission. However, under certain conditions (eg, prolonged immobiliza-tion, thermal burns), these receptors may proliferate sufficiently to affect subsequent neuromuscular transmission.
- #11 The magnitude of the end plate potential is directly related to the amount of acetylcholine released. If the potential is small, the permeability and the end plate potential return to normal without an impulse being propagated from the end plate region to the rest of the muscle membrane. At least two additional types of acetylcholine receptors are found within the neuromuscular apparatus. One type is located on the presynaptic motor axon terminal, and activation of these receptors mobilizes additional transmitter for subsequent release by moving more acetylcholine vesicles toward the synaptic mem-brane. The second type of receptor is found on perijunctional cells and is not normally involved in neuromuscular transmission. However, under certain conditions (eg, prolonged immobiliza-tion, thermal burns), these receptors may proliferate sufficiently to affect subsequent neuromuscular transmission.
- #14 amyotropic lateral sclerosis Spasticity:gen. regidity of the muscles.CNS mediated Trauma— exc of nociceptors--exaggurated stretch reflex—inc.contractions—regidity of muscles.
- #18 Result of cl channel opening-hyperpolarization,difference between resting potential & threshold potential is increased,rate of firing is reduced.GABAb-presynaptic..inhibit ca entry inhibitory..dec.neurotransmitterrelease.GABAb post synaptic K+ channel..opening..hyperpolarization gabaA..cl channel post synaptically
- #22 Acts at presynaptic gaba receptors(agonist) decrease the release of glutamate & aspartate
- #23 Go linked. Activate K channels.inhibit Ca influx
- #30 Produced skeletal muscle paralysis,in 16th century in south america.used to kill animals
- #33 DOA;succinyl;5-10 min,atra,roc, vec-20-35 mins,pan;more than 35, tubo;more than 50 Vec&rocu undergo hepatic& billiary excretion Atra..hofman.cisatracurium is an isomer of atracurium.
- #37 When small doses of nondepolarizing muscle relaxants are administered, they act predominantly at the nicotinic receptor site by competing with acetylcholine. The least potent nondepolarizing relaxants (eg, rocuronium) have the fastest onset and the shortest duration of action. In larger doses, nondepolarizing drugs can enter the pore of the ion channel ( Figure 27–1 ) to produce a more intense motor blockade. This action further weakens neuromuscular transmission and diminishes the ability of the acetylcholinesterase inhibitors (eg, neostigmine, edrophonium, pyridostigmine) to antagonize the effect of nondepolarizing muscle relaxants
- #39 When small doses of nondepolarizing muscle relaxants are administered, they act predominantly at the nicotinic receptor site by competing with acetylcholine. The least potent nondepolarizing relaxants (eg, rocuronium) have the fastest onset and the shortest duration of action. In larger doses, nondepolarizing drugs can enter the pore of the ion channel ( Figure 27–1 ) to produce a more intense motor blockade. This action further weakens neuromuscular transmission and diminishes the ability of the acetylcholinesterase inhibitors (eg, neostigmine, edrophonium, pyridostigmine) to antagonize the effect of nondepolarizing muscle relaxants
- #40 Dibucaine inhibits the normal enzyme upto 80% and abnormal enzyme upto 20%. Circulating levels of plasma cholinesterase influence the duration of action of succinylcholine by determining the amount of the drug that reaches the motor end plate
- #45 can not be depolarized again due to desensitization of the membrane. Cause: Channel block may be the cause of this phase & channel behaves like in a prolonged closed state - exact mechanism not clear
- #47 Raised intraocularb pressure due to inc. contractions ofmyofibrilsmyalgias due to unsynchronized contractions of adjacent muscles. Release from intracellular sites Caution in: Patients receiving digoxin or diuretics