General anaesthetics (GAs) cause a controlled and reversible loss of consciousness, analgesia and amnesia, but despite having been in use for over 150 years, the precise mechanism of action of commonplace GAs is still not fully understood. A variety of compounds with widely different chemical structures can act as GAs. Central nervous system (CNS) areas affected by GAs include the cerebral cortex, thalamus, reticular activating system and spinal cord, and potential molecular targets include GABA, NMDA, serotonin (5-HT) and glycine receptors, as well as voltage-gated ion channels. GAs are delivered intravenously (IV) or are inhaled, by specially trained anaesthesiologists who must closely monitor the patient's vital signs during the procedure. Muscle relaxants (neuromuscular blockers) such as pancuronium, rocuronium, vecuronium, atracurium, mivacurium, and succinylcholine are used alongside the GA agents. The effect of these neuromuscular blockers can be reversed at the end of surgery by administration of anticholinesterase drugs (e.g. neostigmine).
Following a premedication step, general anaesthesia is described as a four stage process: Stages 1-3 represent the safe clinical window during which surgery can proceed, stage 4 must be avoided.
Several different types of drug are given together during general anaesthesia.
Stage 1: induction - is the time between administration of the drug and loss of consciousness. Administered IV or by inhalation.
Stage 2: excitement - this stage is characterised by erratic breathing and heart rate, and is associated with a vomiting risk. Modern, fast-acting drugs have been designed to limit the time spent in stage 2.
Stage 3: surgical anesthesia - during this stage muscles relax, motor reflexes are blunted, vomiting stops, breathing is depressed and eye movements cease. Anaesthesia is then maintained for the duration of the procedure using IV or inhalational anaesthetics.
Stage 4- overdose- administration of medication overdose causes brain stem or medullary suppression and leads to respiratory and cardiovascular collapse.
Malignant hyperthermia is a rare but potentially lethal complication of anaesthesia, most commonly associated with use of the volatile anaesthetics. This condition is characterised by a rapid rise in temperature, increased muscle rigidity, tachycardia, and acidosis. Dantrolene sodium is used in the treatment of malignant hyperthermia.
A teaching slide set (29 in total) describing the mechanisms of action and clinical use of local anaesthetics. This session is a basic introduction to the pharmacodynamics and pharmacokinetics of local anaesthetics. It is aimed at preclinical medical or dental students, or students in the early years of a pharmacology degree. Contributed by Clare Guilding, Newcastle University Medicine Malaysia.