28 - Principles of General Anaesthesia Flashcards
What is general anesthesia and its clinically desirable effects?
CLINICALLY DESIRABLE EFFECTS:
- Loss of consciousness
- Suppression of reflex responses
- Relief of pain (analgesia)
- Muscle relaxation
- Amnesia
However, only all the general anaesthetic drugs do the first two. The other effects vary between the different agents.
At what doses do some of the clinically desirable effects of general anaesthesia occur?
Loss of Consciousness - low concentration
Suppression of Reflex Responses - high concentration
Outline the history of general anaesthesia
Crawford Long (1842)
- ether
Horace Wells (1845)
- nitrous oxide
William Morton and Charles Jackson (1846)
- ether
What are the two methods by which general anesthetics are administered?
Gaseous/Inhalation
Intravenous
Give examples of general anaesthetics that are gaseous/inhaled
Nitrous Oxide
Diethyl Ether
Halothane
Enflurane
Give examples of general anaesthetics that are administered intravenously
Propofol
Etomidate
What is the Meyer/Overton Correlation?
Anaesthetic potency increases in direct proportion with oil/water partition coefficient
The more lipid soluble, the better the anaesthetic
What are the problems with the Meyer/Overton Correlation?
PROBLEMS:
- At relevant anaesthetic concentrations, change in bilayer are very little
- This change would impact membrane proteins, but this was never well explained
What are the molecular targets of intravenous general anaesthetics?
Reduced Neuronal Exictability or Altered Synaptic Function
GABAA receptors
- enhance inhibitory effects of GABA
- promotes hyperpolarisation of cells and tissues
Specific GABA subunits are present in different areas of the brain:
β3
- lots in spinal cord and lower brainstem
- suppression of reflex responses
α5
- found in hippocampus
- amnesia
What are the molecular targets of inhalational general anaesthetics?
Reduced Neuronal Exictability or Altered Synaptic Function
GABAA or Glycine Receptors
Effect GABA receptors less effectively than intravenous agents
GABAA
α1
- suppression of reflex responses
Glycine Receptors
- inhibitory role in brainstem and spinal cord
Neuronal Nicotinic ACh Receptors
- as you increase dose of anaesthetic, activation of receptor goes down
- anaesthetics could inhibit these receptors
- do not seem to contribute to the hynoptic effects
TREK (Background Leak) K+ Channels
- Important in terms of consciousness
- Mediate transition from sleep to consciousness
Nitrous Oxide
- no effect on GABA
- blocks NMDA-type glutamate receptors
- probably compete with co-agonist glycine
What does this diagram tell you?
Summary of the molecular targets of different general anaesthetics
Dark green or pink spot indicates significant potentiation or inhibition, respectively.
A light green or light pink spot indicates little potentiation or inhibition, respectively.
Tells Me:
Intravenous act through GABA but have very mild effects on other targets
Inhalational have many targets and are far less selective
Where in the neuroanatomy is linked to loss of consciousness?
LOSS OF CONSCIOUSNESS
- links to RAS
- normally, RAS sends signals to cortex to keep people conscious via thalamus
- anaesthetics suppress RAS neurones and decrease the relay
The reticular activating system (RAS) emanates from the brainstem and projects upward to the cerebral cortex via the thalamus. All the cortical varieties of consciousness depend upon the integrity of these subcortical structures. Acetylcholine is released from cholinergic nerve terminals projecting from RAS to the thalamus and cortex in highest concentrations in association with cortical activation that occurs naturally during wakefulness.
Consciousnessdepends on feedback loops between cortex, thalamus and reticular activating system. Sensory information received by the cortex is the primary starting point for consciousness.
Anaesthetics can directly hyperpolarize thalamocortical neurons by activating TREK channels and/or by potentiating GABAAreceptors- information transfer through the thalamus is disrupted. Although the thalamus might control the state of consciousness, processing in the cortex is responsible for the detailed content of consciousness, and during anaesthetic-induced LOC the cortex is profoundly deactivated.
Where in the neuroanatomy is linked to suppression of reflex responses?
SUPPRESSION OF REFLEX RESPONSES
Depression of reflex pathways in the spinal cord
- decrease relay from spinal cord to brain
High density of GABA receptors located in the dorsal horn of the spinal cord
Where in the neuroanatomy is linked to amnesia?
AMNESIA
Decreased synaptic transmission in hippocampus/amygdala
Memory is particularly sensitive to general anesthetics because amnesia occurs at concentrations well below those that cause sedation and analgesia. Although the ratio of the GABAA receptor subunits that have α5 is low, they are distributed at the extrasynapse of the hippocampus in a relatively high ratio. Therefore, it can be assumed that general anesthetics potentiate the tonic currents acting on the α5GABAA receptor in the hippocampus, which can be considered as one of the amnesia mechanisms that occur during anesthesia.
What is the difference between inhalation and intravenous general anaesthetics with regards to how they access the brain?
Intravenous goes straight into blood, then brain
Inhalation needs to get into the blood from the lungs
What is the blood:gas partition coefficient?
BLOOD:GAS PARTITION COEFFICIENT
Describes how a gas will partition itself between two phases after equilibrium has been reached
Low Blood:Gas Coefficient
- inhale drug and it ends up in the lungs
- large proportion of the drug doesn’t dissolve into the blood
- lots of drug remains in gas phase
- can access brain a lot quicker
- fast speed of brain penetration
- quick anaesthetic
- can also be cleared very quickly and exhaled easily
- allows for quick control of anaesthesia
High Blood:Gas Coefficient
- higher uptake of gas into blood
- dissolves well in blood
- slower induction time
- longer until the equilibrium with the brain partial pressure of the gas is reached
What are the properties of inhalation anaesthetics compared to intravenous anaesthetics?
Inhalational agents can cause coughing/excitatory phenomena (seizures)
Which general anaesthetics tend to be used in a clinical setting?
Intravenous agent given first = Propofol (fast induction)
Inhalation agent given next = Enflurane (easy to control)
Other drugs used for other properties
