Anaesthetics

Anaesthesia is a controlled temporary loss of awareness, with varying degrees of pain relief (analgesia), loss of memory (amnesia) and muscle paralysis. Involves 3 agents:

1) General Anaesthetic

Believed to potentiate GABA receptors and K+ channels and inhibit excitatory NMDA receptors.

2) Opioid pain relief

e.g. fentanyl + sufentanil – Provides very fast acting pain relief 

3) Muscle relaxant

e.g mivacurium or succinylcholine – Blocks the NMJ to stop muscle reflexes 

Inhalation Anaesthetics

These are complete anaesthetics as they cause loos of consciousness + analgesia/amnesia + immobility
– The potency is measured by the Minimum Alveolar Concentration (MAC) = Minimum concentration of anaesthetic in alveoli that results in immobility in 50% of patients when exposed to noxious stimuli
– As the potency of the agent increases, the lower the MAC value will be.

For inhalation anaesthetics, the solubility of the gas in air vs blood is measured by blood-gas coefficient:

For low solubility gases, it means few molecules need to be present in blood to increase partial pressure.

– Therefore, this gives rapid equilibrium in CNS with rapid onset action + rapid elimination
– Increasing cardiac output decreases induction rate, as presents larger volume into which gas dissolves
– For high solubility, means slower induction + slower elimination as it redistributes into fat.

Nitrous Oxide (N20)

This is often useful as a combination drug, as it increases uptake rate of gas anaesthetics

– It lacks potency for surgical anaesthesia + no muscle relaxant properties 

Side effects
  • Postoperative nausea
  • Vomiting
Isoflurane/Desflurane/Halothane
These are inhalation anaesthetics which give rapid induction and emergence

Sevoflurane

This gives rapid induction with rapid recovery, widely used in paediatrics

– Also causes bronchodilation, useful for patients with respiratory difficulties. 

General Side effects
  • Agents cause a reduction in the BMR and the set point for thermoregulation, giving vasodilation and hypothermia
  • Malignant hyperthermia –> a rapid increase in muscle metabolism due to mutations of the ryanodine receptor, occurring after use with GA halothane usually

Symptoms:

  • Tachycardia
  • Muscle spasm
  • Hyperthermia

Treatment:

  • Dentrolene (stops Ca2+) release from SR

 

IV Anaesthetics

e.g. Propofol

This is a commonly used agent for quick sedation, given IV and has a short duration of efficacy.
– Widely used for many surgical procedures giving minimal side effects 

Side effects
  • Systemic hypotension from vasodilation

Etomidate

This is an alternative to Propofol and thiopental for rapid-onset, short-duration anaesthesia 

Ketamine

This is an antagonist of NMDA receptors, so decreases glutamergic transmission
– It has similar MOA to Memantine – NDMA antagonist used to treat Alzheimer’s Disease
– Produces a special type of anaesthesia giving analgesia and amnesia without the loss of consciousness
– Also, it is a cardiovascular stimulant for people in shock 

Side effects
  • Distortions of reality
  • Hallucinations

LOCAL ANAESTHETICS

These drugs cause a transient reversible loss of sensation without a loss of consciousness.
– They are classified as either esters or amides.
– They both act by blocking voltage-gated sodium channels in the inactivated state.
– All local anaesthetics are vasodilators, and so they are given with adrenaline to reduce systemic absorption

Amides – Lidocaine (suffix = -caine)
Lidocaine has a rapid onset and intermediate duration of action (1-2 hours)
– It is are used for minor procedures, epidurals and spinal anaesthesia (+anti-arrhythmic)

 Esters – Procaine + Tetracaine + Benzocaine
Procaine has a short duration of action and so is used for infiltration anaesthesia
– Tetracaine is long acting and so is used for spinal anaesthesia and ophthalmology use.

General Side effects
  • CNS (dizziness, sedation, tremor)
  • Cardiovascular (bradycardia + hypotension)
Sources

Image 1: John D’Orazio, Stuart Jarrett, Alexandra Amaro-Ortiz and Timothy Scott / CC BY (https://creativecommons.org/licenses/by/3.0) 2.

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