Neuromuscular Blockers in Anaesthesia with monitoring
- 3. Voltage gated calcium channels P channels - Not affected by ccb. - Affected by calcium entry blocking drugs - Also blocked by bivalent cations (mg) Activates voltage gated and calcium activated potassium channel--- depolarize Post tetanic potentiation - In tetanic stimulus, calcium enters but can’t get out fast enough, resulting in accumulation inside the nerve terminals. Eaton-lambert syndrome- antibody against vgcc. Weakness. Increased sensitivity to muscle relaxants.
- 4. Release of acetylcholine Release of acetylcholine vesicles – fusion, docking, exocytosis Mediated by SNARE grp of prtns SYNAPSIN- frees vesicle from cytoskeleton SYNAPTO-TAGMIN- helps to carry vesicle to ca rich membrane area and Stabilizes for docking. Target of botulinum toxin. SYNAPTO-BREVIN (vesicular membrane) forms complex with SYNTAXIN, SNAP 25 (nerve terminal membrane).
- 7. Fate of synaptic vesicles Binding Release Kiss and run Briefly opens Completely collapses into the membrane instantly Compensatory Stay open longer Do not completely collapse Stranded Stays open till next stimulus Completely Collapses but not released till next stimulus
- 8. MEPP Small release of acetylcholine vesicles in resting state. (Quantal) Miniature end plate potential Summation- if reaches threshold (-45)-- ap
- 9. Acetyl choline receptor (Nm) Adult/ junctional Foetal/ extra junctional Location End Plate On muscle surface Component 2 alpha, 1 beta, 1 delta, 1 epsilon 2 alpha, 1 beta, 1 gamma, 1 delta Sensitivity to Ach More Single channel Conductance Low Duration of opening Longer (2-10x) T 1/2 2 weeks 24 hrs
- 10. Neuronal Variant (New Discovery) 5 apha7 subunit. Present in skeletal muscle in sepsis, immobilization, denervation. All alpha subunit can bind to Ach. More sensitive to choline. No desensitization Can lead to large amount of K release Can cause Resistance to NDMR
- 11. Perijunctional Sodium Channels • Activation Gate (Voltage) • Time Gate Time gate open • at rest • Both Gates has to be open for ion transfer Voltage Gate opens • When depolarization current arrives. • Can’t close till depolarization current is over • Normal AP propagation. • Sch fasciculation Time get closes • End of AP • Can’t re-open till Voltage gate is closed. • MOA for Sch paralysis
- 13. NMJ Diseases
- 15. Miller Fischer Syndrome (variant of GBS) MFS is thought to be an autoimmune process in which a preceding infection stimulates production of an antibody that reacts to a glycolipid found on neuronal membranes, causing demyelination and loss of function of the peripheral nerves. In most people with Miller Fisher Syndrome (96%) an antibody called anti- GQ1b is identified. The GQ1b antigen is located on the Schwann cells of the ocular cranial nerves
- 16. NMJ Disease
- 17. Lambert Eaton Vs Myasthenia Gravis
- 18. Succinyl Choline- partial Agonist Dose- 0.5-1.5 mg/kg TBW 70kg BW- 50mg/ml- 2 ml Obese- 1mg/kg TBW Onset- 30-60 sec Duration- 5- 10 min
- 19. Contra indications- o Burns o Extensive Denervation of skeletal Muscle o Major Trauma o Children (unrecognized muscular dystrophy) o Open eye surgery
- 20. Side Effects • Cardiac Dysfunction- • Mimics acetyl choline in cardiac post ganglionic muscarinic receptors. • Highest Incidence- 2nd dose of Scoline, 5 min after the initial dose. • Atropine provides some protection (2-4 min before)
- 21. Side Effects • Hyperkalaemia- • Due to sutained opening of extrajunctional receptors. Usually, 0.5mg • Exacerbated in prolonged denervation, muscle injury (burns, ICU, Trauma) • CKD does not exacerbate. Can be used if no uraemic neuropathy.
- 22. Side Effects • Myalgia- • caused due to unsynchronized contraction. Can also lead to increased CPK, Myoglobinuria. • can be prevented by pre-curarizing dose of NMDB •Pre curarizing dose- Atra -0.03 mg/kg Vec – 0.007 mg/kg • Eg- 65 kg BW • Atra 10mg/ml- 0.2 ml • Vec 1mg/ml- 0.5 ml 3-4 mins Sch 2 mg/kg • Sch 50mg/ml- 2.6 ml
- 24. Side effects Increased IOP ,ICP, IGP Instead of brief contraction like in skeletal muscles, causes prolonged contraction of intra ocular muscles Draws the eye close to orbit Raises IOP as much as 20g for 5-10 mins To avoid in open eye surgery or cases with increased IOP. Malignant Hypertension
- 25. Atypical PseudoCholinesesterase • Dibucaine number is a measure of Functional Quality of Pseudocholinesterase. • No relation with quantity • CLD- normal dibucaine number, prolonged Sch apnoea due to quantity deficit.
- 26. Phases of Sch Block Phase 2 block start at 5-7 mg /kg
- 27. NDMR NON DEPOLARIZING MUSCLE RELAXANT, NON-COMPETITIVE ANTAGONIST
- 28. Types of NDMR AMINO STEROID No release of histamine Cardiovascular stable BENZYL ISOQUINOLINE Releases Histamine (can be reduced by slow injection) Leads to vasodilation Hypotension and tachycardia Bronchospasm Flushing Cardiovascular Stable
- 29. Histamine release Dose dependent- threshold- atra 0.5mg/kg, miva 0.2 mg/kg Rate of injection- slow injection prevents. Good practice to inject over 40-60 sec. Pretreatment with H1,H2 blocker Repeated Dose Lower Histamine release.
- 30. Duration Based Classification Amino Steroid Benzyl Isoquinolone Pancuronium Long Acting Doxacurium Vecuronium Intermediate Acting Atracurium Rocuronium Cis atracurium Rapacuronium Short Acting Mivacurium
- 31. Dosing of NMBD
- 32. Maintenance dose- 20% of induction dose 65 kg IBW 1mg/ml- 1.3ml 10mg/ml- 1ml 10mg/ml- .7ml
- 33. Rocuronium Dose- 0.6-1.2 mg/kg IBW 65kg BW- 10mg/ml- 8 ml Onset- 60-120 sec Duration- 30-60 min (60 with RSI dose of 1.2mg/kg) Metabolism- liver S/E- bradycardia
- 34. Atracuronium Dose- 0.5 mg/kg IBW 65kg BW- 10mg/ml- 3 ml Onset- 3-5 min Duration- 25-30 min Metabolism- Hoffman Degradation (Temperature Sensitive) S/E- Histamine Release Metabolic by product- Laudanosine Accumulate in prolonged infusion Can cause Seizure
- 35. Drug Interaction- Potentiation 1. Volatile Anesthetic- Des>Sevo>Iso> N2O, Opiod > Propofol. Reduce dose of NMB by 15-20%. 2. Mg 3. Antibiotic- Aminoglycoside, Polymixin, Clindamycin
- 36. Drug Interaction- Faster Recovery 1. Calcium 2. Carbamazepine, phenytoin 3. Aminophylline
- 37. Some Diseases
- 38. NM Monitoring
- 39. Synapse Physiology- Few Terms Synaptic Fatigue- Synaptic fatigue is a decrease in the number of discharges by the postsynaptic membrane when excitatory synapses are repetitively and rapidly stimulated. Mechanism - exhaustion of the stores of neurotransmitter in the synaptic vesicles. Unmasked in MG Post-tetanic Facilitation- Post-tetanic facilitation is increased responsiveness of the postsynaptic neuron to stimulation after a rest period that was preceded by repetitive stimulation of an excitatory synapse. Mechanism- increased release of neurotransmitters due to enhanced local concentrations of intracellular calcium.
- 40. Types of Current Threshold Current- Lowest current required to elicit any detectable muscle response. Maximal Current- Current which generates contraction in all muscle fibers. Supramaximal Current- 25% higher current than Maximal Current. 2-3x than threshold current.
- 41. Single Twitch Stimulation 1 supramaximal stimuli at 0.1 hz Used during induction
- 42. TOF • 4 Supramaximal stimuli given at 0.5 sec interval. •TOF Count •TOF ratio •Fade
- 44. Tetanic Stimulus
- 45. Post Tetanic Count Stimulation (PTC)
- 47. Double Burst Stimulus (DBS)
- 48. Which monitoeing to use when
- 52. Facial Nerve
- 55. Reversal
- 56. TOF relation to clinical
- 61. S/E • Maximal effect within 10 min • No value of repeat dose • Don’t combine two anticholinesterase • Volatile Anesthetics reduce speed of recovery. Sevo>iso
- 63. Suggamadex
- 64. Features o Cyclodextrin with 8 glucose molecules o Roc> Vec> Pan o Binds with Roc in 1:1 fation and makes a water soluble compound. o Acts only on the Plasma, Not NMJ o No Serious adverse effect
- 65. Is it better than Neostagmine?
- 66. Limitations of NM Monitoring