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Fundamentals of Pharmacology > General Anaesthetics > Flashcards

General Anaesthetics Flashcards

1
Q

What is the triad of general Anaesthesia?

A

Need for unconsciousness
Need for analgesia
Need for muscle relaxation (loss of reflexes)

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2
Q

How do general anaesthetics work?

A

By depressing CNS activity

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3
Q

What is the general structure of inhalational anaesthetics?

A

Simple unreactive compounds
short chain molecules
no one chemical class

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4
Q

What is the lipid theory?

A

lipid solubility / water hydrophobicity is important in creating general anaesthesia as the concentration of the agent to immobilise tadpoles is inversely proportional to its lipid:water partition coefficient.

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5
Q

Explain the subsequent observations of the lipid theory?

A

Anaesthetic in cell membrane 0.05 mM of any agent of anaesthetic.
Anaesthesia occurs when volume of lipid expanded by 0.4%
High pressure reverses the anaesthesia

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6
Q

How do anaesthetic agents induce anaesthesia?

A

Agents act by volume expansion of lipid cell membrane and therefore increases fluidity of the cell membrane. This leads to the interference with conduction of nerve impulses.

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7
Q

What is the Protein Theory?

A

Uses the lipid theory and lipid solubility idea to explain that it is needed to provide access for proteins .

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8
Q

What evidence is there for the protein theory?

A

Cut-off phenomenon anaesthetic potency –> for homologous series of long chain anaesthetic compounds.

Increased chain length, increases lipid solubility but anaesthetic potency stops beyond an certain length. (size matters)

Stereo selectivity of anaesthetic potency is preserved with protein binding.

Anaesthetics may bind to hydrophobic pockets on proteins.

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9
Q

Why is stereo selectivity important?

A

Suggests that mirror images (optical isomers) may have one orientation that is more effective than the other if that orientation is the only one that can fit into its target site.

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10
Q

What are the molecular targets for general anaesthetics?

A

Ion channels (no single target)

GABAa receptors
K channel

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11
Q

What would anaesthetics targeted to GABAa receptors cause?

A

Increased inhibition

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12
Q

What would anaesthetics targeted to K channels cause?

A

Leads to activation and therefore decreased membrane excitability

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13
Q

What are some possible other anaesthetic targets?

A 
Excitatory ligand gated channels
NMDA receptor (glutamate), 5-HT, nACh
Glycine
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14
Q

What are the major effects of anaesthetics on the CNS function?

A 
Decreases neurotransmitter release
Decrease post synaptic responsiveness
Can depress activity in the entire CNS.
Unconsciousness mediated by action at reticular formation in the midbrain
Analgesia action at the thalamus.
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15
Q

What are the concentration dependent effects of anaesthetics in their order of lowest conc to highest?

A

Memory loss
Consciousness
movement
CVRS response

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16
Q

What is the narrow therapeutic window for anaesthetics?

A

2-3 x clinical dose leads to over dose

17
Q

What is the 2nd stage of anaesthesia?

A

Delirium (induction phase):
Excitement, delirium, incoherent speech loss of consciousness, unresponsive to non-painful stimuli,

Dangerous phase:
muscle rigidity, spasmodic movements, cardiac arrhythmias, vomiting, choking

18
Q

What is the 3rd phase of anaesthesia?

A

Surgical anaesthesia:
unresponsive to painful stimuli breathing regular abolition of reflexes muscle relaxation synchronised ElectroEncephaloGraph

19
Q

What is the 4th stage of anaesthesia?

A 
Medullary paralysis (overdose):
pupillary dilation respiration/circulation ceases; EEG wanes  death
20
Q

What is the 1st stage of anaesthesia?

A

I ANALGESIA drowsiness; reflexes intact; still conscious

21
Q

What makes a good anaesthetic agent?

A

Should be potent and fast acting

22
Q

What is MAC?

A

Measure of anaesthetic potency in man

Minimal Alveolar Concentration:
the concentration of anaesthetic in the alveoli required to produce immobility in 50% of patients when exposed to a noxious stimulus
(variables are patient’s sex, height and weight)

23
Q

How is MAC expressed?

A

expressed as % of inspired air (% v/v)

24
Q

What is MAC inversely proportional to?

A

Lipid solubility

ie. The more soluble in lipids/oils, the lower the [anaesthetic] in the patients inspired air required to produce anaesthesia

25
Q

What is the main determinant of anaesthetic potency?

A

Lipid solubility

26
Q

Why is speed of induction important?

A

Needs to be fast acting so it goes through the dangerous phase quickly before it reaches anaesthetic phase, but also must be recovered from quickly

control over depth of anaesthesia

27
Q

What are the main factors influencing rate of induction?

A

Properties of anaesthetic

Physiological factors

28
Q

How do anaesthetics get access to the brain?

A

Equilibration between different compartments

Transfer to the alveoli (increased anaesthetic conc increases speed of induction)

Transfer to blood (solubility in blood must be low to increase speed of induction as this means that blood will be saturated more quickly before the brain is anaesthetised.

High rate of pulmonary blood flow to brain.

Tissue blood partition coefficient of 1 leads to brain anaesthesia fastest

Tissue blood flow (high in lean tissue and therefore fast transfer)

29
Q

What is the main factor of anaesthesia induction?

A

Blood:Gas partition coefficient (lamda) is inversely proportional to the speed of induction.

30
Q

How are most inhaled anaesthetics eliminated?

A

Mainly via the lung

Metabolism not important for most anaesthetics

31
Q

What are factors of IV anaesthetics?

A

Rapid onset
Short acting

Commonly used for induction
can be used alone for short procedures

32
Q

What are the molecular targets for IV anaesthetics?

A

Potentiation of GABAa receptor action

33
Q

What type of anaesthesia does Ketamine produce?

A

Dissociative anaesthetic:

sensory loss, analgesia and paralysis without loss of conscious

34
Q

How does ketamine work?

A

Antagonism of NMDA receptor

35
Q

What are some adjuncts to general anaesthetics?

A

Premedication - Benzodiazepines, Opioids, Antimuscarinics

Muscle relaxants (deeper anaesthesia) - Benzodiazepines, neuromuscular blockers

Anti-emetic (decrease nausea) - metoclopramide

Fundamentals of Pharmacology (19 decks)

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