Thiopentone Flashcards
Describe the contents of the Thiopentone ampoule
- Pale yellow powder –> reconstituted fors a 2.5% solution.
- Sodium Carbonate 6%
- Nitrogen in place of air
Define tautomerism
Dynamic interchange between two forms of a molecular structure, often precipitated by a change in the physical environment
Describe tautomerism in thiopental
Thiopentone is a WEAK ACID
There are two forms
- Keto form (Physiological pH)
- Insoluble in water
- Soluble in fat - Enol form (Alkaline environment)
- Soluble in water
- Insoluble in fat
So sodium carbonate in the preparation reacts with water to form sodium bicarbonate –> pH 10.5. Favours water soluble enol tautomer.
Also, Nitrogen is used instead of air. CO2 in air would react with air to release H ions –> more acidic environment reducing enol form and water solubility.
What is the dose of Thiopentone for induction of anaesthesia
3 - 7 mg/kg
What are the EEG findings with a sodium thiopental infusion and what does this mean in terms of CMRO2
Isoelectric EEG meaning the cerebral metabolic rate of oxygen consumption reaches its maximal reduction.
What % of the Thiopentone given is available to act on the brain. And why? Why is there still a anaesthetic effect despite this
Thiopentone is a weak acid with pKa is 7.6
20% free (unbound)
Of this free 20% –> 12 % is unionized at physiological pH and 8% (of the 20%) is ionized
So 12% of the is available.
Anaesthetic effect still observed due to
- High lipid solubility
- Large cardiac output brain receives
Describe the pharmacokinetic reasons for the reason why reduced Thiopentone is needed in critically ill patients for the same clinical effect
Critical ill patients tend to be acidotic
Thiopentone is a weak acid: Acids ionize at physiological pH above their pKa
Reduced physiological pH
- More unionized drug
- Fewer protein binding sites available for binding (acidosis)
Therefore, less drug administered to critically ill patients –> same physiological effect.
How do NSAIDS affect unbound drug portion after thiopentone administration
NSAIDS are highly protein bound –> fewer sites available for protein binding –> Increased unbound thiopentone –> less drug required for same clinical effect
What is tri-exponential decline with regard to thiopentone pharmacokinetics
Rapid redistribution of Thiopentone after administration into
- Well perfused regions (Brain/Liver)
- Muscle and skin
The final decline is due to:
3. Hepatic oxidation to inactive metabolites
What happens if Thiopentone is given as an infusion and why
Metabolism may become linear (zero order) due to saturation of hepatic enzymes.
What effect does Thiopentone have on the P450 system
It induces the cytochrome P450 enzymes
Describe the effects of Thiopentone on the organ systems
CNS
- General anaesthesia in 20 seconds for 5 - 10 mins
- Reduced CBF, CMRO2, ICP
- Antiepileptic
- Antalgaesic (low dose)
CVS
1. dose dependent reduced CO, SV, SVR with compensatory tachycardia
RSP
- RSP depression
- Laryngospasm
- Bronchospasm
Renal
- Reduced urine output
- -> reduced CO
- -> reduced ADH (decreased CNS function)
May precipitate porphyria
List the anaesthetic drugs that are unsafe and those that are safe in porphyria
UNSAFE
Thiopentone and other barbiturates
Etomidate
Halothane
Lidocaine
Clonidine Metaclopramide Hyoscine Ranitidine Diclofenac Cocaine
SAFE Propofol Sux Roc Paracetamol Dex Morphine Fentanyl Neostigmine Glycopyrrolate Ondansetron
What happens subsequent to intra-arterial injection of thiopentone. Why does this not happen with intravenous drug administration
INTRA-ARTERIAL
Enol to keto form shift –> not water soluble –> precipitation of thiopental crystals which become wedged in blood capillaries –> ischaemia and pain
INTRAVENOUS
Continuous dilution by more and then more venous blood which allows dissolution of the crystals.
What is the treatment of intra-arterial injection of thiopentone
- Intra-arterial injection of papaverine or procaine,
- Analgaesia
- Sympathetic block of the limb
- Anticoagulation
