Flashcards in CPTP 3.23 Neuropharmacology 8 General anaesthetics Deck (42)
Do local anaesthetics have a hydrophobic or a hydrophilic group?
Both. They are amphiphilic
One drug has a pKa of 7.9. Another has a pKa of 8.9. Which has more of its neutral form?
The drug with a pKa of 7.9 (which happens to be lidocaine)
pKa is dissociation constant, so higher number means more ionised form
How are general anaesthetics administered?
• Inhalation (volatile anaesthetics)
• Injections (liquid anaesthetics)
What is the triad of anaesthesia?
The three things that is required of a general anaesthetic:
• Muscle relaxation
How is the triad of anaesthesia usually achieved?
No agent provides all three so is achieved by using combinations of drugs and adjunct medicines. Depends on the surgery needed (i.e. intubation needs lots of relaxation)
What are the three kinds of adjunct medications in surgery?
• Medication given before surgery
• Medication given during surgery
• Medication given after surgery
What are benzodiazepines used for in surgery?
• Presurgery anxiolysis for extremely stressed patients
• Presurgery amnesia to make them not remember 'going under'
What are H2 blockers used for in surgery?
Give an example drug
To prevent gastric acid secretion in high-risk GORD (or pregnant) patients and prevent them breathing in gastric acid
What are antimuscarinic drugs used for in surgery?
Give an example drug
Decrease salivary secretions and bradycardia during surgery
Name the formulary neuromuscular blocking drugs and what they are used for
Suxamethonium and Atracurium
• Suppress muscle tone for fine surgery
What is the mechanism of action of suxamethonium?
Depolarising neuromuscular blocking drug
• Activates the acetylcholine receptor so much that it enters a state whereby it can no longer generate an EPSP
Describe the solubility of general anaesthetics
In general, how do general anaesthetics work?
Reducing neuronal activity in the CNS by decreasing excitatory activity and increasing inhibitory activity (in particular the reticular activating system)
What adverse effects can result from general anaesthetics?
There is a very fine line of a therapeutic window between sedation and:
• Cardiovascular depression
• Respiratory depression
What are the theories of the mechanisms of action of general anaesthetics?
• Lipid solubility theory - anaesthetic effect is exerter through some perturbation of the lipid bilayer
• Anaesthetic effect is exerted through interactions with proteins
Describe the lipid solubility theory of general anaesthetic mechanism of action
What observation supports this?
Anaesthesia results when a sufficient amount of anaesthetic dissolves in the lipid bilayer to perturb the physical properties of that layer, altering the excitability of proteins within it.
The Meyer-Overton Rule:
• General anaesthetics which are more soluble in lipids are more potent
What evidence overturns the lipid solubility theory of general anaesthetics?
• Not all small lipid-soluble molecules are general anaesthetics
• Not all general anaesthetics are small lipid-soluble molecules
• Stereoisomers of existing anaesthetics do not work as general anaesthetics
Which proteins are interacted with in the structural theory of general anaesthetics?
Which of these is the 'most important' protein, which all anaesthetics are thought to work on?
GABA-A is the most important receptor
How do general anaesthetics work on GABA-A receptors?
When anaesthetic is present, GABA is enhanced, and stays on the receptor for longer, thus allowing in more Cl- and hyper-polarising the cell
Which formulary general anaesthetics are inhaled?
• Nitrous Oxide
What causes loss of consciousness when inhaling nitrous oxide recreationally?
What is nitrous oxide used for (with reference to the triad of anaesthesia)?
Good at pain relief
Poor at unconsciousness
Poor at neuromuscular suppression
Which formulary general anaesthetics are intravenously administered?
• Thiopental sodium
What are the stages of anaesthesia, as it anaesthesia is deepened?
Stage 1: Analgesia
Stage 2: Excitement
Stage 3: Surgical anaesthesia
• Regular respiration
Stage 4: Medullary depression (side effects)
• Too far
• Respiratory arrest
• Cardiac arrest
• No eye movement
How is stage 2 moved through as quickly as possible?
Induction of anaesthesia is done with an intravenous anaesthesia
How is anaesthesia administered during surgery? Explain why it is administered in this way.
At the start of surgery: intravenous
• Ensures stages I and II are passed as quickly as possible
During surgery: inhalation
• Maintains the patient steadily in stage III
• This is achieved through a self-regulating negative feedback, whereby too much anaesthesia will depress breathing, reducing the anaesthetic administered
What is level of anaesthesia correlated with when using inhaled anaesthetics?
The partial pressure of the volatile anaesthetic in brain tissue
What is the movement of an inhalation agent driven by?
The partial pressure gradients:
• The pressure generated by a compartment is affected by the partition coefficient of the volatile anaesthetic in blood and body tissue
What is a partition coefficient
A coefficient that represents the solubility of volatiles in different media, and thus the AMOUNT of anaesthetic in each compartment in equilibrium (the only thing that is evened out is the pressure)
e.g. the blood/gas coefficient is the ratio of the amount of anaesthetic dissolved in blood to the amount of the same volume of gas in contact with that blood
• '2' would imply twice the anaesthetic dissolved in blood compared to the amount in alveoli