Flashcards in CNS Pharmacology Deck (299)
Who was the first to demonstrate the usefulness of nitrous oxide as an analgesic in the process of tooth extraction?
William Morton was known for his use of ether as a volatile anaesthetic during tooth extraction, T or F?
What was J. Simpson’s contribution to general anaesthesia?
He was the first person to demonstrate that chloroform could render patients’ unconscious. Was also deemed the co-discoverer of general anaesthetics
What are the two classes of chemical general anaesthetics?
Inhalational and intravenous
What type of general anaesthetic is NO2?
Inhalational chemical general anaesthetic
Give an example of some intravenous chemical general anaesthetics?
Halogenated hydrocarbons such as isoflurane. Also steroids and barbiturates such as thiopental are also intravenous
Give some examples of physical general anaesthesias?
Low pressure, hypothermia
What is meant by the term surgical anaesthesia?
The point at which patients become unresponsive and unable to sense pain
What evidence is there to suggest that anaesthetics aren’t agonists acting on a receptor?
Steep dose-response curve which isn’t seen in agonist binding. Low pressure can also induce anaesthesia
What is significant about the dose-response curve of general anaesthetics?
They have very steep dose-response curves
What property of general anaesthetics is very closely related to their potency?
Describe what is meant by a MAC value and how this relates to the potency of the general anaesthetic?
MAC value – minimum alveolar concentration of anaesthetic to alleviate a response to surgical incision in 50% of patients. The lower the MAC value the higher the potency of the general anaesthetic
What is meant by the oil:gas partition coefficient?
The ease with which a substance dissolves, or partitions into oil
Drugs with a low oil:gas partition coefficient will have a high potency and thus a lower MAC value, T or F?
F – drugs with higher oil:gas partition coefficients will have a high potency and lower MAC values
What is meant by the Meyer-Overton rule?
The effect of an anaesthetic is proportional to the molar concentration of the agent in lipid
What is the effect of general anaesthetics on the plasma membrane?
General anaesthetics lead to a volume expansion in the plasma membrane
What is the impact of general anaesthetics on lipid fluidity?
General anaesthetics increase lipid fluidity
What aspects of the general anaesthetic mechanism of action are explained by the lipid theory?
As antibiotics are thought to lead to a volume expansion of the plasma membrane and an increase in lipid fluidity the lipid theory of antibiotic action accounts for the meyer-overton rule. In addition, the effect of pressure is also explained as we know that a decrease in pressure results in a volume expansion of the lipid membrane and thus will give rise to anaesthesia. Finally this also accounts for the fact that such a diverse range of compound can have anaesthetic effects
What aspects of the general anaesthetic mechanism of action aren’t explained by the lipid theory?
The fact that decreasing temperature can have anaesthetic effects despite the fact that it leads to a decrease in membrane fluidity. It also doesn’t explain that the binding of anaesthetics is saturable, implying a specific interaction with a protein. Finally there is a loss of actions in some compounds that are extremely lipid soluble and being homologous to known anaesthetics
It in fact turned out that the mechanism of action of anaesthetics was a combination of the lipid theory and a protein binding theory, T or F?
What is significant about the binding sites of anaesthetics that have been proven to bind to proteins in the plasma membrane?
General anaesthetic binding sites tend to be in hydrophobic domains deep within the membrane
What type of proteins do general anaesthetics tend to bind to?
Which specific receptor is it known that some general anaesthetics bind to and how does this lead to anaesthesia?
GABAA receptors – inhibition of regions in the central nervous system leading to anaesthesia
Different anaesthetics all interact with the same subunits of the proteins to which they bind, T or F?
F – different anaesthetics bind to different subunits
Where to intravenous anaesthetics tend to bind on the GABAA receptors?
Where in the GABAA receptor structure do volatile liquid general anaesthetics tend to bind?
The interface between the α and β subunits
What is the function of the two-pore-domain potassium channels?
Regulate the excitability of neurons
How do general anaesthetics that bind to the two-pore-domain potassium channels exert their effects?
Increase the excitability of the channels and make the firing of actions potentials less likely
Explain ketamine’s anaesthetic effect?
Ketamine is an NMDA receptor antagonist and is known as a dissociative anaesthetic which prevents the action of excitatory glutamate