Anaesthetic Drugs (DONE)

Question 1

Mechanisms of general anaesthetics

Answer 1

Three phenomena must be explained by any proposed mechanism of action of a general anaesthetic:
Loss of conscious awareness
Loss of response to noxious stimuli
Reversibility

Question 2

Molecular theories of mechanisms

Answer 2

Overton and Meyer 1896
Linear correlation between potency of anaesthetic and lipid solubility
Site of action likely highly lipophilic (cell membranes)
However, ketamine is an extreme outlier and etomidate is a stereoisomer

Question 3

Membrane lipids

Answer 3

Critical volume hypothesis
Perturbation theory
One theory is that anaesthetics dissolve into lipid membrane, membrane expands, distorts Na/K channels, preventing depolarisation

Question 4

Protein sites of action

Answer 4

Interaction (excitatory) at inhibitory neurotransmitter channels- GABA, glycine
Interaction (inhibitory) at excitatory neurotransmitter channels- NMDA, nicotinic

Question 5

GABA

Answer 5

Binding sites for GABA associated with the a subunit

Modulatory sites: a/g interface- benzodiazepines, b- etomidate, thiopentone, propofol, volatiles

Question 6

Glycine receptor

Answer 6

Major inhibitory neurotransmitter
Receptor associated with a chloride channel
Volatile anaesthetics all potentiate the actions of glycine

Question 7

NMDA

Answer 7

Activated by glutamine
Modulated by magnesium
Inhibited by ketamine and nitrous oxide

Question 8

Targets: neuroanatomy

Answer 8

Evidence from neuroimaging studies
Most sensitive areas of brain- midbrain reticular formation, thalamic sensory relay nuclei and to a lesser extent parts of the cortex
Disruption of information transfer through the thalamus and brainstem

Question 9

Intravenous anaesthetics

Answer 9

Agents that will induce unconsciousness in one arm-brain circulation time

Question 10

Ideal properties of IV anaesthetic

Answer 10

Non-toxic, long shelf life at room temperature, water soluble formation, no interaction with any other agents, rapid onset, no hypersensitivity reaction, analgesic in sub-anaesthetic concentrations, no excitation or emergence phenomena, no histamine release, not emetic, no pain on injection, high lipid solubility, rapid recovery, safe following inadvertent intra-arterial injection

Question 11

Thiopentone

Answer 11

Barbiturate
Sodium salt, pale yellow powder
Formulation contains calcium carbonate
Nitrogen in place of air
Gives alkaline solution with pH 10.5
Induction dose: 3-7mg/kg

Question 12

Thiopentone effects

Answer 12

CVS: dose dependent reduction in cardiac output, stroke volume and resistance, compensatory tachycardia
CNS: reduction in cerebral oxygen consumption, reduction in cerebral blood flow, reduction in CSF pressure, rapid general anaesthesia lasting 5-10 mins
Resp: dose dependent respiratory depression, can cause laryngospasm and bronchospasm
Contraindicated in patients with porphyria

Question 13

Propofol

Answer 13

1%/2% emulsion
Contains soya bean oil and egg white protein
Weak acid
Induction dose: 1-2mg/kg

Question 14

Propofol effects

Answer 14

CVS: dose dependent resistance resulting in drop in BP, reduction in myocardial contractility, compensatory tachycardia rare
CNS: excitatory effects seen in 10% patients, some patients demonstrate choreifrom movements
Resp: respiratory depression leading to apnoea, cough and laryngospasm rare
Pain on injection, may turn hair and urine green, antiemetic effect

Question 15

Ketamine

Answer 15

Three concentrations available: 10, 50 and 100mg/ml
Water soluble, forms an acidic solution pH 3.5-5.5
IV (1-2mg/kg) or IM (5-10mg/kg)
General anaesthesia and sedation
Chronic pain

Question 16

Ketamine effects

Answer 16

CVS: sympathetic nervous system stimulation, increase in HR, cardiac output, BP
CNS: dissociative anaesthesia, analgesia, unpleasant dreams, hallucinations, emergence phenomena, increases cerebral blood flow, intracranial pressure
Resp: patent airway, bronchodilation

Question 17

Etomidate

Answer 17

Induction dose 0.3mg/kg

Produces least CVS disturbance, but suppression of adrenocortical function