What is dissociative anasthesia?
inhibits transmission of nerve impulses between higher and lower centres of the brain
Name 4 inhalational anaesthetic agents
N2O, isoflurane, desflurane, sevoflurane
Name 2 IV anaesthetic agents
Which anasthetics act on GABA LGIC?
How do anasthetics that work on GABA LGICs work?
bind to GABA(A) and increase sensitivity to GABA and increase chloride currents, hyperpolarising neurone and decreasing its excitability.
Glycine activated chloride channels anasthetics - How does this exert an effect?
Increases sensitivity to glycine to increase chloride currents. Hyperpolarises neurones and decreases its excitability.
How do anasthetics that block nAChRs work? What effects does this have on the patient?
reduces excitatory Na currents caused by ACh binding. Contributes to analgesia and amensia rather than sedation
Which anasthetics work on NMDA receptors? How do they work?
e.g. nitrous oxide and ketamine
Binding at NMDA reduces calcium currents
What compounds is the principle anasthetic agent mixed with?
oxygen, air, and often nitrous oxide.
Define minimal alveolar concentration
MAC - percentage of inhaled anasthetic that abolishes response to surgical incision in 50% of patients.
Lower MAC value = more potent anasthetic
At how many MACs is surgical depth usually achieved?
1.2 - 1.5
Why is nitrous oxide given alongside the inhaled anasthetic?
Reduces the MAC for individual agents.
What is the blood:gas coefficient?
Describes the volume of gas in litres that can dissolve in one litre of blood.
Higher blood:gas cofficient = more readily it will enter blood
What 2 factors affect the distribution of anasthetic around the body?
Relative blood supply to each organ and the specific tissue uptake capacity for the anasthetic
What is the relative blood supply to the organs at rest?
brain, liver and kidneys = 75%
Muscle = 20%
fat = 5%
How are modern fluranes metabolised?
does not undergo metabolism
Why does full recovery from anasthetics take hours to days? What factors affect recovery?
As the drug moves out of its compartments to be excreted from the lungs it is free to redistribute around the body during circulation and gain entry back into the CNS, affecting consciousness.
Duration of recovery related to legnth of procedure and amount of anasthetic in muscles and fat.
How long does inhalational agents and IV agents take to get sufficient anasthetic depth?
Inhalational - minutes
IV - <20 seconds
How is propofol metabolism?
Undergoes hepatic and extrahepatic conjugation, half life of 2 hrs.
Explain the pharmacodynamics of anasthetics that affect GABA and glycine
Increase the potency of GABA and glycine receptors. This means a lower level of GABA or glycine is needed to produce the same effect.
Also increase relative efficacy of GABA or glycine so that binding of any channel results in more chloride current allowed to flow - Positive allosteric modulation
Explain the pharmacodynamics of anasthetics that affect the excitatory LGIC such as NAChR or NMDAR
Efficacy of excitatory ligand decreases as the anasthetic antagonist inactivates the receptor non-competitively. The bound receptors have reduced efficacy but the remaining unbound receptors have unchanged efficacy.
Overall effect is to reduce inward movement of excitatory currents.
What adjuvant is given to induce anxiolysis and amnesia?
benzodiazepines e.g. midazolam
What adjuvant is given for rapid induction of deep initial sedation
What adjuvant is given for analgesia and reducing main inhalational agent MAC?
What adjuvant is given only for analgesia?
Opioids e.g. morphine or fentanyl. Fentanyl much more potent.
What adjuvant is given for neuromuscular blocking to abolish reflexes and induce muscular relaxation?
tubocurarine or pancuronium - competitive nAChR antagonist
Succinylcholine - depolarising agonist of nAChR
Why does using more than 1 drug allow for finer control of anasthetic depth?
Can exert certain effects without risking more serious side effects by increased anasthetic depth e.g. neuromuscular blockade can be achieved without changing MAC.
What ADRs can result from fluranes?
cardio and resp depression
increased ICP - cerebral blood flow increases due to decreased vascular resistance
What ADRs can result from nitrous oxide?
expansion of airway cavities
Diffusion hypoxia - In recovery, NO diffuses rapidly out of blood into alveoli, decreasing alveolar o2 conc.
What ADRs result from propofol and opiates?