Thiopentone

Question 1

What chemical class does thiopentone belong to?

Answer 1

Thiobarbiturate

Question 2

What physicochemical properties does thiopentone have?

Answer 2

Highly lipid soluble
Weak acid, pKa 7.6
60% in unionized form, which is more lipid soluble
70-80% plasma protein bound

In vial = 500mg thiopental sodium salt and sodium carbonate. Mixed with 20ml H2O = 2.5% solution (25mg/ml) at pH 10.5 (high pH to stop acid preciptating)

Question 3

What are common SEs of thiopental?

Answer 3

Extremely painful and limb threatening if injected intra-arterially
Hypersensitivity 1:15000
Absolutely contraindicated in porphyria

Question 4

What are the CVS effects of thiopentone?

Answer 4

Direct myocardial depression with hypotension and decrease in CO (use with caution in hypovolaemia)

Question 5

What are the RS effects of thiopentone?

Answer 5

Dose dependent decrease in minute volume, commonly short period of apnoea

Question 6

How is thiopentone metabolised?

Answer 6

In the liver to active oxybarbiturate derivative pentobarbitol and 2 other inactive metabolites

Question 7

What is the onset/offset of thiopentone?

Answer 7

Onset 30seconds

Offset 5-10 mins

Question 8

What are the uses of thiopentone?

Answer 8

Induction of anaesthesia
Status epilepticus
To achieve burst suppression in raised ICP

Question 9

What is the MOA of thiopentone?

Answer 9

Increased duration of opening of GABA Cl- channels in CNS causes hyperpolarisation and neuronal inhibition

Question 10

What is the absorption/distribution of thiopentone?

Answer 10

80% protein bound
Of the 20% unbound - only 12% un-ionized and available (as 60% ionised at pH 7.4)
Vol of distribution = 2 L/kg
Rapid emergence secondary to rapid redistribution to tissues
Critically ill patients are acidotic with reduced protein binding = less thio needed
NSAIDS may decrease protein binding and increase free drug fraction

Question 11

What is the metabolism and excretion of thiopentone?

Answer 11

Hepatic oxidation by P450 mainly inactive metabolites (though pentobarbitone is active)
Induces P450 after single dose
Zero order kinetics with infusion

Question 12

What are the CVS effects of thiopentone?

Answer 12

Decreased CO
Decreased SV
Decreased SVR
May cause increased HR

Question 13

What are the RS effects of thiopentone?

Answer 13

Resp depression
Laryngospasm
Bronchospasm

Question 14

What are the CNS effects of thiopentone?

Answer 14

Anaesthesia
Decreased blood flow, volume and CSF pressure
At low dose is antalgesic

Question 15

What are the renal effects of thiopentone?

Answer 15

Decreased urine OP (increases ADH and decreases CO)

Question 16

What are the general SEs of thiopentone?

Answer 16

Severe anaphylaxis (1:20000)
Precipitates porphyria
Intra-arterial injections causes severe pain and spasm and perivascular necrosis

Question 17

What is the dose of thiopentone?

Answer 17

3-7 mg/kg IV

1g / 22 per kg weight PR

Question 18

What are the chemical properties of thiopentone?

Answer 18

Displays tautomerism or dynamic isomerism - the proportions of the 2 forms governed by ambient pH

Weak acid - forms alkaline solution with dissolved in water, ph 10.8 (Solution is stable for days and is bacteriostatic because of high pH)

pKa 7.6 (60% unionised at pH 7.4)

Highly lipid soluble

Question 19

What is thiopentone stored as?

Answer 19

Sodium carbonate (6% by weight) added to powder
When dissolved releases OH- to prevent accumulation of H+ and formation of undissociated acid
Stored under N2 gas - prevents acidification of powder by CO2 in air