[UMP021] Pharmacology Of General Anaesthesia Flashcards
How is general anaesthesia often defined?
As a drug-induced reversible loss of consciousness
How do you define consciousness? In some form or other a lack of responsiveness is often taken as the measure of anaesthesia
- eg “can u open ur eyes”, or lack of responsiveness to a painful stimulus
What measure is the relative effectiveness of general anaesthetic often compared by?
ED50
What is ED50
The dose (or concentrations) that is effective in 50% of the population being tested
= dose/ concentration which, on average, is effective in putting 50% of a population to sleep
How is potency in the field of anaesthesia defined
Reciprocal of ED50
Ie (1/ED50)
When you need high concentration of drug, drug is not very potent
General anaesthetic are usually split into two classes of agent. What are these classes?
Intravenous agents and inhalational agents
Pros n cons of inhalational anaesthetic agents
Pros:
- possible to very precisely control concentration of anaesthetic the patient equilibrates with, by altering partial pressure of anaesthetic agent in ‘air’ —> makes anaesthesia relatively safe, despite narrow safety margin
Cons:
- for some inhalational agents, takes q awhile for individuals to reach unconsciousness (not v helpful esp if patients nervous)
Pros n cons of intravenous anaesthetic agents
Pros:
- able to render patients unconscious quickly
Cons:
- often more difficult to control (so they have not, traditionally been sued to maintain anaesthesia)
What are inhalational anaesthetic agents usually used for
Used to maintain anaesthesia during long operations
Give examples of intravenous anaesthetic agents
- propofol
- etomidate
- Thiopentone
What is the mechanism of action for intravenous agents propofol, etomidate and thiopentone
Enhancement of GABAA
- enhance at relatively Low and hence clinically relevant concentrations
- ## etomidate enhancement of GABAA is stereoselective ( + isomer more potent than -)
Examples of inhalational anaesthetic agents
Desflurane, isoflurane, sevoflurane (they are often combined with nitrous oxide)
Older anaesthetics include Halothane, enflurane (these are less widely used)
Mechanism of action for volatile agents halothane, enflurane and isoflurane
- able to enhance GABAA receptor activity at clinically relevant concentrations like intravenous agents
However this activation is less than that w intravenous, and their mechanism of action less certain - most likely target more than one protein type
- all three of these agents also able to enhance activity of glycine receptors at clinically relevant conc
Which anaesthetic gases activate the potassium channel TREK-1 at clinically relevant concentration
Nitrous oxide,
Cyclopropane
Xenon
Mechanism of action of nitrous oxide, cyclopropane and xenon
These anaesthetic gases do not appear to activate GABAA receptors
- all three do activate potassium channel TREK-1 at clinically relevant concentrations
- nitrous oxide and xenon also able to inhibit NMDA receptors at clinically relevant conc
Benefits of xenon
And why is it not used more widely?
Benefits:
- Low blood solubility = anaesthesia can be induced rapidly
- lacks vasodilatation effects compared to other agents
- Low toxicity
- several studies have shown that it may protect neuronal cells against ischaemic injury
Limitations: cost and limited availability of this gas
What does ‘dissociative anaesthesia’ mean?
Meaning that in addition to analgesia,
There’s
- marked sensory loss
- amnesia
- paralysis
BUT WITHOUT LOSS OF CONSCIOUSNESS
Which drug produces profound analgesia, but ‘dissociative anaesthesia ‘
Ketamine
Ketamine’s theorised mechanism of action target
May also target NMDA receptors and this may account for its neuroprotective effects
Conventional stages of anaesthesia, which are somewhat arbitrary
Stage I: analgesia. Still conscious but becoming insensitive to pain (not all generate anaesthetic agents are good analgesics)
Stage II: excitement. Delirium and excitement. Respiration irregular
Stage III: surgical anaesthesia. Unconscious. Respiration and reflexes progressively depressed as anaesthesia deepens
Stage IV: medullary compression. No spontaneous respiration and depressed vasomotor centres. Coma and death follow in absence of artificial respiration and circulatory support
How is the potency for inhalational anaesthetics commonly expresssed as
Minimum alveolar concentration (MAC)
- despite its name, it is an eD50 thiiugh expressed as conc in air, not blood
Minimum alveolar concentration (MAC)
What is it
Alveolar concentration (% by volume) of inhalational anaesthetic which will, when equilibrium has been attained, prevent movement response to surgical incision in 50% of individuals
What is the relationship between solubility of anaesthetic agents and rate at which anaesthetics are absorbed
Rate at which anaesthetic are absorbed is faster for less-soluble agents
Why do less soluble anaesthetic agents get absorbed faster
Less-soluble agents like nitrous oxide have a larger MAC
Concentration in inspired air therefore much higher, so amount of anaesthetic required to produce effective blood concentrations can be delivered faster
With a soluble agent like halothane or methoxyflurane, MAC Low
So amount present in lungs Low, even if all were extracted into blood, would not be enough to raise blood concentration very much at each inspiration
Solubility of inhalational anaesthetics and relationship with rate of elimination after stopping administration
Elimination after stopping administration is faster for anaesthetics with Low solubility eg nitrous oxide
(Slower for halothane or methoxyflurane)
