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

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

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

4. General anaesthesia: hypnosis Putting someone ‘to sleep’ Usually IV, then maintained with inhalational agents Inhalational in children Onset/ offset MetabolismUseCommon examples DrugCardio/Resp effect Other comments IVRapidLiverInduction of anaesthesia in most cases PropofolHypotension+ Depress ventilation No hangover effect ThiopentoneHypotension+ Depress ventilation Hangover effect KetamineMinimal ventilation depression or hypotension Used in war Dissociative anaesthesia Hallucinations InhalationalSlowAlmost none – “blown-off” by alveolar gas exchange Maintenance (cheap) Inducing kids IsofluraneDepress ventilation + hypotension Desflurane SevofluraneSmells pleasant

5. General anaesthesia: muscle relaxation To understand muscle relaxants, we need to understand the neuromuscular junction. Order these steps at the NMJ… Action potential arrives at motor nerve terminal Voltage-gated Ca2+ channels open allowing Ca2+ influx Increase in intracellular [Ca2+] causes fusion of presynaptic vesicles to cell membrane and release of Acetylcholine by exocytosis 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) Upon reaching threshold an AP occurs in the muscle Acetylchloinesterase hydrolyses Ach to choline and acetate, which are recycled

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. When would you need to give drugs for muscle relaxation? Intubation (insertion of tube into trachea) Surgery requires muscles relaxed e.g. abdominal surgery 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 What are the TWO categories of muscle relaxant? Depolarising Non-depolarising General anaesthesia: muscle relaxation

8. THREE examples? How does a non-depolarising muscle relaxant work? Competes with ACh and blocks nAChR 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 General anaesthesia: muscle relaxation 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. How can local anaesthetic toxicity occur? Local anaesthetics 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. http://www.fastbleep.com/medical-notes/other/15/31/528 Although level of detail is probably more appropriate for clinical years Fastbleep notes: Regional anaesthesia Resources