1. Anaesthesia Emily Matthews (e.k.matthews@warwick.ac.uk)

2. Three ‘types’ of anaesthesia • General • Regional (e.g. spinal, brachial plexus block, femoral nerve block) • Local What is anaesthesia? Loss of sensation What is GENERAL anaesthesia? Drug-induced loss of sensation + loss of consciousness Decreasing level of consciousness Extreme unresponsiveness – no voluntary behaviour Tolerate unpleasant procedure. Verbally rousable

3. General anaesthesia What is the triad of general anaesthesia? Analgesia Musclerelaxation Hypnosis /unconsciousness

4. General anaesthesia: hypnosis • Putting someone ‘to sleep’ • Usually IV, then maintained with inhalational agents • Inhalational in children

5. General anaesthesia: muscle relaxation To understand muscle relaxants, we need to understand the neuromuscular junction. Order these steps at the NMJ… Ach diffuses across the synaptic cleft and binds to nAChR on postsynaptic  membrane. nAChR is a Na+/K+ channel – it opens and there is Na+ influx Na+ influx generates action potential in the motor endplate called an endplate potential (EPP) Increase in intracellular [Ca2+] causes fusion of presynaptic vesicles to cell membrane and release of Acetylcholine by exocytosis Acetylchloinesterase hydrolyses Ach to choline and acetate, which are recycled Upon reaching threshold an AP occurs in the muscle Action potential arrives at motor nerve terminal Voltage-gated Ca2+ channels open allowing Ca2+ influx

6. General anaesthesia: muscle relaxation 1. Action potential arrives at motor nerve terminal 2. Voltage-gated Ca2+ channels open allowing Ca2+ influx 3. Increase in intracellular [Ca2+] causes fusion of presynaptic vesicles to cell membrane and release of ACh by exocytosis 4. ACh diffuses across the synaptic cleft and binds to nAChR on postsynaptic  membrane. nAChR is a Na+/K+ channel. It opens and there is Na+ influx 5. Na+ influx generates action potential in the motor endplate called an endplate potential (EPP) 6. Upon reaching threshold an AP occurs in the muscle 7. Acetylchloinesterase hydrolyses ACh to choline and acetate, which are recycled

7. General anaesthesia: muscle relaxation When would you need to give drugs for muscle relaxation? • Intubation (insertion of tube into trachea) • Surgery requires muscles relaxed e.g. abdominal surgery What are the TWO categories of muscle relaxant? • Depolarising • Non-depolarising How does a depolarising muscle relaxant work? Similar structure to Ach so binds to nAChR at NMJ Example? • Side-effects • Fasciculations • K+ efflux can lead to hyperkalemia Suxamethonium • Important points about ‘sux’: • Cannot be reversed – wait for it to wear off in 3-5mins • Wears off as broken down by pseudocholinesterase. People deficient in this enzyme get suxamethonium apnoea and stop breathing for up to 2hrs

8. General anaesthesia: muscle relaxation How does a non-depolarising muscle relaxant work? Competes with ACh and blocks nAChR THREE examples? • Atracurium • Rocuronium • Vecuronium • Hoffman degradation – not dependent on liver/kidneys pH and temperature dependent. Why might you need to ‘reverse’ muscle relaxation? • End of operation to allow patient to breathe on their own • Failed intubation – wake patient up, let them breathe on their own Reversal agents: • Atracurium: anticholinesterases e.g. neostigmine and pyridostigmine. Inhibit acetylecholinesterase which breaksdown Ach, thus more Ach available to compete with muscle relaxant • Rocuronium and vecuronium: drug called sugammadex (expensive)

9. Local anaesthetics How do local anaesthetics work? Block Na channels Examples? Lidocaine (still pronounced “lig-no-caine”) Bupivicaine – slower onset, longer lasting Why can local anaesthetics give a ‘mobile block’ (loss of sensation, motor function retained)? Larger diameter, myelinated motor fibres less sensitive to anaesthetic than sensory fibres

10. Local anaesthetics How can local anaesthetic toxicity occur? • Intravascular injection Signs and symptoms? • Paraesthesia of tongue and lips • CNS • Drowsiness • Seizures • Muscle twitching • CVS • Hypotension • Bradycardia • Cardiac arrest Related to Na channel blocking action

11. Resources • Fastbleep notes: • Regional anaesthesia http://www.fastbleep.com/medical-notes/other/15/31/528 Although level of detail is probably more appropriate for clinical years