Katzung 12th ed - Chapter 25 - General Anaesthetics - Intravenous (1) Flashcards
What class of drug is thiopentone?
Thiopentone is an ultra-short-acting barbiturate given IV.
Describe the basic pharmacodynamics of thiopentone and phenobarbitone.
Bind to GABA receptors, prolong the duration of chloride channel opening, causing inhibition of action potential propagation. These can cause sedation, hypnosis, and anticonvulsant activity.
Describe the distribution of thiopentone.
Thiopentone is highly lipid-soluble, and achieves plasma:brain equilibrium within one minute of IV administration.
What is the duration of action of thiopentone? What pharmacokinetic feature of thiopentone determines the offset of its CNS effects?
Duration of action is 20-30 minutes, due to its rapid redistribution from CNS to skeletal muscle and adipose tissues.
Describe the metabolism and elimination of thiopentone and phenobarbitone.
Both are metabolized SLOWLY in the liver to produce water-soluble inactive metabolites that are excreted in the urine.
Describe the basic pharmacodynamics of propofol.
Propofol potentiates the inhibitory effect of GABA and glycine, causing hypnosis. It is used for both induction and maintenance of anaesthesia.
What dose of propofol is given to achieve sedation?
0.5 - 1 mg/kg.
What dose of propofol is given to achieve anaesthesia?
2-2.5 mg/kg.
Describe the cardiovascular adverse effects of propofol.
Reduced PVR –> hypotension.
Negative inotrope.
How is propofol presented?
As an oil in water emulsion.
Describe the metabolism and excretion of propofol.
Rapidly metabolized in the liver (10 times faster than thiopentone) and excreted in urine.
In one word, explain what largely determines the offset of CNS effect of propofol.
Redistribution.
What is the distribution half-life of propofol?
What is the elimination half-life of propofol?
Distribution half-life 2-8 minutes.
Elimination half-life 30-60 minutes.
What is the volume of distribution of propofol: small or large? Why?
Small Vd, due to being 90% protein-bound.
What do we know about the mechanism of action of ketamine?
Largely unknown, but it may involve blockade of glutamate (NMDA) receptors.
What is the IV dose of ketamine to achieve anaesthesia for a short surgical procedure?
1-4mg/kg, given slowly over 60 seconds.
Describe the cardiovascular adverse effects of ketamine.
By causing inhibition of noradrenaline reuptake, ketamine causes increased HR, BP and cardiac output. It is a positive inotrope.
Name one CNS adverse effect that happens in 12% of patients receiving ketamine.
Emergence phenomena: disorientation, sensory and perceptual illusions, vivid dreams.
Describe the distribution of ketamine.
Highly lipid soluble, rapidly distributed to all tissues.
How is ketamine metabolised and excreted?
Hepatically metabolized. Renally excreted.
What is meant by an anaesthetic agent’s alpha half-life? And the beta half-life?
Alpha half-life refers to the Distribution half-life.
Beta half-life refers to the Elimination half-life.
Which is metabolized more slowly: Ketamine or Propofol? Which one has a longer duration of effect?
Ketamine is metabolized more slowly (beta half-life 2.5 hours) than Propofol (beta half-life 0.5-1 hours).
Ketamine and Propofol both have a very similar onset (30 seconds) and duration of action (alpha half-lives both about 2-10 minutes)
Which IV anaesthetic agent causes raised ICP?
Ketamine
What is an “added bonus” effect of propofol, aside from its anaesthetic effects?
It has anti-emetic properties.
