Anaesthetics Flashcards
What are some inhalation and IV anaesthetics?
Inhalational: Nitrous oxide N2O Isoflurane Desflurane Sevoflurane
Intravenous
Propofol
Ketamine
What are effects of general anaesthesia?
- Sedation to the point of unconsciousness
- Amnesia
- Muscle relaxant
- Reflex suppression
- Immobilisation
- Anxiolysis
- Analgesa
No one drug can produce all these effects, so we use anaesthetics + adjuvants.
What are the different types of anaesthesia?
General anaesthesia
Regional
Local
Dissociative
Describe general anaesthesia
General anaesthesia affects the whole body – you use IV and inhalational anaesthetics, plus adjuvants, which reversibly inhibit sensory, motor and sympathetic nerve transmission – produces unconsciousness and absence of sensation
Describe regional anaesthesia
Regional anaesthesia involves rendering a region of the body insensate by inducing a blockade of transmission between it and the spinal cord. Examples include spinal and epidural anaesthesia. The patient remains conscious but may also be given adjuvants
describe local anaesthesia
Local anaesthesia is a more defined peripheral nerve block – you inject a local anaestheric. Used for tooth extraction, or procedures on the hand, fingers, foot or big toe, or internally in the urethra.
Describe dissociative anaesthesia
inhibits transmission of nerve impulses between higher and lower brain centres with drugs like ketamine – used in children and the elderly for short procedures. Can cause post-operative hallucinations in people outside these groups.
What area is responsible for immobilisation? Unconsciousness? Amnesia?
Immobilisation - spinal cord
Unconsciousness (inhaled agents) thalamus
Amnesia (inhaled agents) hippocampus
What is potency? how can it be predicted?
Concentration of a drug needed to attain 50% of its therapeutic effect
It is predicted by lipid solubility - ability to enter cell membranes
How are fluranes administered?
• Inhalational anaesthetics are vaporised
o Modern inhalational fluranes are volatile liquids at rooms temperature
• Then the agent is mixed with oxygen, air, and often nitrous oxide, which is supplied to the respiratory system via a mask
What is the minimal alveolar concentration?
Minimal Alveolar Concentration (MAC) is defined as the percentage of inhaled anaesthetic that abolishes the response to surgical incision in 50% of patients.
The lower the MAC, the more potent the anaesthetic. The MAC is also a unit of delivery – there is very little variation in MAC between individuals, and so surgical depth can be achieved with 1.2-1.5 MAC. This is why they need to be precisely controlled!
What are the MAC of fluranes?
1-6% by volume
Describe what absorption of anaesthetic is dependent on.
Absorption of the anaesthetic is determined by the blood:gas coefficient of the anaesthetic – the agent will easily pass down its concentration gradient from the alveoli into the bloodstream – the degree of absorption is determined by the blood-gas coefficient – it is the volume of gas (in liters) which can dissolve in one liter of blood. For example for isoflurane its 1.4 – the higher the coefficient the more easily it will enter the blood. The concentration in the alveoli directly determines the concentration reached in the CNS.
Describe what distribution of anaesthetic is dependent on
Distribution is dependent on blood supply to the organs and tissues, and the capacity of that tissue to take up the anaesthetic. 75% of the blood supply goes to the brain, liver and kidneys, 18% to muscle and 5% to fat.
The tissue:blood coefficient determines how the tissues take up anaesthetic from the blood. For example for isoflurane the tissue:blood coefficient is 1.6, so for the same volume of brain to blood the brain will take up 1.6 times as much anaesthetic. But the muscle:blood coefficient is much higher 0 so the muscle takes up proportionately more than the brain. The fat:blood coefficient is even greater – 45 – which provides a reservoir of anaesthetic which redistributes during recovery.
Describe metabolism of fluranes
Fluranes also undergo plasma protein binding – but this is weak and dissociates rapidly.
Fluranes are not significantly metabolised – there is a little transformation by hepatic enzymes.
Describe elimination of anaesthetic fluranes
Elimination: the anaesthetic is withdrawn ensuring adequate oxygenation. The blood concentration of anaesthetic drops and the anaesthetic moves out of the cell membranes and into the venous blood. It is then returned to the alveoli and excreted unchanged by the lungs. The well perfused tissues (brain, liver and kidney) are the first to surrender their anaesthetic, followed by muscle then finally fat. Full recovery can take hours to days (since muscle and fat have high capacity for anaesthetic and lower perfusion – and the anaesthetic they release into the blood can be redistributed back to the CNS – and affect conscious function)
Describe the administration and distribution of propofol
IV bolus leads to rapid distribution to the CNS as it is well perfused, less distribution to muscle and fat. They are heavily bound to proteins in plasma therefore affected by competitive binding.
It then rapidly redistributes (after about 5 minutes) into muscle and fat. You may then continue to dose by bolus or infusion as an adjunct to lower the MAC of flurane. It can be used alone for short surgical procedures
Describe the metabolism and elimination of propofol
Metabolism + elimination: undergoes hepatic and extrahepatic conjugation, so it has a half-life of 2 hours – doesn’t contribute to prolonged post-procedural hangover.
What ion channels do anaesthetics work on?
GABA activated chloride channels (Inhibitory Ligand gated ion channel) - propofol
Glycine activated chloride channels (inhibitory LGIC)
Neural Nicotinic Acetylcholine Receptors (excitatory LGIC)
NMDA receptors (excitatory LGIC)
Describe the MOA of anaesthetics binding to GABA activated chloride channels
Propofol
Once anaesthetics have bound they increase sensitivity to GABA, increase chloride currents, and so hyperpolarise the neurone and decrease excitability
Increases potency of inhibitory ligand + increase efficacy (binding a channel = more chlorine flows)
This is positive allosteric modulation
Describe the MOA of anaesthetics binding to Glycine activated chloride channels
Structurally related to the GABAA ligand gated ion channel. Anaesthetics bind and increase sensitivity to glycine, increase chloride currents, hyperpolarises the neurone and decreases excitability. They act in the spinal cord to reduce the response to noxious stimuli
Increases potency of inhibitory ligand + increase efficacy (binding a channel = more chlorine flows)
This is positive allosteric modulation
Describe the MOA of anaesthetics binding to neural nicotinic acetylcholine receptors
Anaesthetics inhibit subtypes of the nicotinic acetylcholine receptor, which reduces excitatory sodium currents. This contributes to analgesia and amnesia.
Unchanged potency, decreased efficacy – non-competitive allosteric antagonism
Describe the MOA of anaesthetics binding to NMDA receptors
Nitrous Oxide and Ketamine – reduce the calcium current, reducing synaptic transmission
Unchanged potency, decreased efficacy – non-competitive allosteric antagonism
What are used for anxiolytics and amnesia as an adjuvant to fluorine? MOA?
• Benzodiazepines are used for anxiolysis and amnesia. An example is Midazolam. They agonise GABAA receptors. They are given IV an hour before surgery. They carry only a low risk of cardiovascular and respiratory depression and can be used as sedatives for short procedures.
