Drug Classification: Anaesthesia

Propofol

UNDER REVIEW (September 2016)

Mechanism of Action:

Short-acting intravenous agent used for the induction of general anesthesia or for short operations. Mode of action is unknown, but there is evidence that it interacts with the GABA(A) receptor to mimic GABA or to potentiate its actions. Since GABA is an inhibitory neurotransmitter in the CNS, GABA-mimetics will depress the CNS leading to loss of consciousness.

Lecture and CAL materials:

 

Isoflurane

UNDER REVIEW (September 2016)

Mechanism of Action:

Isoflurane is a halogenated ether used for inhalation anesthesia. It is a volatile liquid. The mode of action, as with most inhalation agents, is unknown but was generally thought to involve non-specific pressure-dependent actions on cell membranes, which lead to loss of consciousness. These membrane actions are presumed to disrupt the propagation of nerve impulses as a consequence of depressant actions at excitatory synapes (e.g. glutamatergic), or facilitatory actions at inhibitory (e.g. GABAergic) synapses within the CNS. Current evidence from neurophysiological patch clamp studies on neurones suggest that the GABAa receptor is probably the primary target for GAs, though exactly how fluorohydrocarbon GAs such as isoflurane, or inert gases such as xenon, interact with the receptor complex and/or the nearby neuronal membrane remains to be established.

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Nitrous Oxide

UNDER REVIEW (September 2016)

Mechanism of Action:

Gaseous inhalation anaesthetic which can also be used as an analgesic (with oxygen: entonox = 50:50 mix). Nitrous oxide is a dissociative agent which causes euphoria and dizziness. The mechanism of action is not completely understood, but it is thought that the gas interacts with the plasma membranes of nerve cells in the brain and thus affects the communication among such cells at their synapses, resulting in anaesthesia. These membrane actions are presumed to disrupt the propagation of nerve impulses as a consequence of depressant actions at excitatory synapes (e.g. glutamatergic), or facilitatory actions at inhibitory (e.g. GABAergic) synapses within the CNS. Current evidence from neurophysiological patch clamp studies on neurones suggest that the GABAa receptor is probably the primary target for GAs, though exactly how nitrous oxide, or inert gases such as xenon, interact with the receptor complex and/or the nearby neuronal membrane remains to be established.

Lecture and CAL materials:

Atracurium

UNDER REVIEW (September 2016)

Mechanism of Action:

Atracurium is a non-depolarizing competitive antagonist acting at the nicotinic ACh receptor (nAChR) on skeletal muscle to cause muscle relaxation. Atracurium binds to the same receptor site as ACh on the muscle end plate, preventing the activation of the receptor-channel complex. It belongs to the non-depolarising class of neuromuscular-blocking drugs (the other class being depolarizing drugs such as suxamethonium – see separate eDrug entry). ACh is released in response to the arrival of an action potential at the nerve ending. The amount of ACh released by the nerve ending and the amount needed to initiate an action potential at the muscle fibre is redundant by several folds. Hence, blocking just a few receptor sites at the muscle end plate will be compensated by the copious amount of ACh activating the remaining receptors. For atracurium to be effective, it needs to block 70-80% of nACHRs at any one muscle fibre. A small muscle end plate potential may still be recorded at the muscle fibre from the remaining nAChRs but this does not exceed the threshold potential required to initiate an action potential at the muscle fibre (all-or-nothing principle of transmission). The degree of muscle relaxation represents the proportion of muscle fibres failing to respond to a nerve action potential. This sort of block can be overcome by increasing the relative concentration of ACh by administration of an anti-cholinesterase drug such as neostigmine (see separate eDrug entry). High levels of ACh will effectively compete with atracurium to occupy nAChR sites on the muscle end plate. Atracurium is designed to spontaneously degrade at physiological plasma pH. It subsequently has a short duration of action and is independent of renal and hepatic function.

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Lidocaine

UNDER REVIEW (September 2016)

Mechanism of Action:

A sodium channel block blocker (Class 1b). Has its major effect on electrically excitable tissues such as cardiac cells and nervous tissues.

  1. Anti-arrhythmic action – reduces the rate of depolarization of cardiac action potential, increases effective refractory period and decreases atrioventricular conduction.
  2. Local anaesthetic effect. Reduces conduction in sensory neurones.

Lecture and CAL materials:

Suxamethonium

Mechanism of Action:

Suxamethonium acts on the neuromuscular junction, as a depolarizing blocker. Compared to non-depolarizing blockers (e.g. atracurium), which are competitive antagonists of acetylcholine (ACh) at the nicotinic receptor (nAChR) in skeletal muscle, non-depolarizing blockers are agonists that activate the nAChR. Suxamethonium causes sustained depolarization at the endplate which prevents normal neuromuscular transmission. Suxamethonium consists of 2 ACh molecules linked by acetyl groups and is broken down by enzyme cholinesterase (AChE). Therefore the duration of action is prolonged in those who have low enzyme levels (genetic variation) or take anticholinesterase drugs.

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