Thiopentone Flashcards
Describe the presentation and pharmaceutical aspects
A pale yellow sodium salt
Reconstituted with sterile water to 500mg in 20mL (2.5% solution)
Vial contains Na2CO3 and nitrogen to increase alkalinity and improve solubility
Reconstituted pH = 11 -> favours the water soluble enol form
Stable for ~1 week
Drug class
Barbiturate
Mechanism of action
Binds to barbiturate binding site on GABAaR
Potentiates GABA on GABAaR inc duration of Cl- opening
Direct effect on GABAaR at high doses
Outline the uses of Thiopentone
Induction of anaesthesia
Refractory status epilepticus
EEG burst suppression (management of refractory elev ICP)
What is the induction dose
2-5mg/kg
What is the pKa and how much is ionised at pH 7.4?
Why is this significant?
pKa = 7.6 (acid)
60% is unionised at pH 7.4
Critically ill pts with an acidosis will have a higher amt of free drug due to dec protein binding and inc fraction of unionised drug -> demonstrates faster onset
How much drug is protein bound?
80%
Onset time and duration time
Rapid onset (30-60 secs), duration is 5-30mins due to distribution Plasma concentration demonstrates a tri-exponential decline -> high BF organs -> low BF organs -> metabolism
Volume of distribution
2.5L/kg (highly lipophilic)
Outline the metabolism
Hepatic (CYP450)
Oxidation to active metabolites - pentobarbitone then inactive
Enzyme pathway is saturable -> demonstrates zero order kinetics
Inactive metabolites are excreted in urine
Elimination half life
6-15hrs
Clearance
3.5mL/kg/min
Outline the cardiovascular effects
Negative inotrope
Dose dependent dec in CO, SV, SVR
Compensatory tachycardia
More pronounced in hypovolaemia, acidosis or red protein binding
Outline the respiratory effects
Dose dependent resp depression
Bronchospasm
Occ laryngospasm
Blunts hypercarbic response
Outline the CNS effects
Dec CMRO2 Dec CBF and cerebral blood volume Dec CSF pressure Complete EEG burst suppression at high doses Dec IOP "Hangover" effect - fatigue and HA
