Barbiturates

Question 1

Is thiopental a weak acid or weak base, and what is it’s pKa?

Answer 1

Weak acid with a pKa of 7.6.

Question 2

What is the volume of distribution of thiopental?

Answer 2

2.2 L/kg

Question 3

What is the clearance rate of thiopental?

Answer 3

3.5 ml/kg/min

Question 4

What is the half-life of thiopental?

Answer 4

6-15 hours. After an induction dose of thiopental, the short duration and rapid emergence is caused by redistribution of the drug to less vessel-rich areas of the body, and not by metabolism. However, after repeated administration of the drug, the metabolism and clearance play a more important role in duration of action than redistribution. At this point, the drug displays zero‑order kinetics, which results in a longer lasting effect and delayed recovery. This is why thiopental is never used for maintenance of anaesthesia.

Question 5

What percentage of thiopental is protein bound?

Answer 5

80%

Question 6

What is the induction dose of thiopental?

Answer 6

3-7 mg/kg

Question 7

What is the pKa of methohexital?

Answer 7

7.9 (it is like all barbiturates a weak acid)

Question 8

What is the volume of distribution of methohexital?

Answer 8

2.0 L/kg

Question 9

What is the clearance rate of methohexital?

Answer 9

11 ml/kg/min.

Question 10

What is the half-life of methohexital?

Answer 10

3-5 hours. Methohexital has an elimination half-life of 3-5 hours with a faster clearance, at 11 ml/kg/min, than thiopental. It causes less cumulation than thiopental and can be used for maintenance of short procedures. Hydroxymethohexitone is its main metabolite, which only has minimal hypnotic activity.

Question 11

What percentage of methohexital is protein bound?

Answer 11

60%. The onset of action of a drug depends on its proportion of unbound drug, the ionized fraction and its lipid solubility. Methohexital has a faster onset of action than thiopental because it has a higher proportion of drug unionized in plasma, and a lower percentage that is protein‑bound.

Question 12

What is the induction dose of methohexital?

Answer 12

1-2 mg/kg. It is 2.7 times more potent than thiopental. Methohexital is used for induction anaesthesia. It is ultra‑short‑acting and is used for short procedures, day case surgery and, most commonly, in ECT. It also has an emerging role in pre-hospital care.

Question 13

What is the volume of distribution of phenobarbital?

Answer 13

0.7 L/kg

Question 14

What is the clearance rate of phenobarbital?

Answer 14

11 ml/kg/min. Ionization and renal elimination are increased after alkalinization of the urine.

Question 15

What is the half-life of phenobarbital?

Answer 15

24-96 hours. Approximately 25% is excreted unchanged in the urine and 75% metabolized in the liver.

Question 16

What percentage of phenobarbital is protein bound?

Answer 16

50-65%.

Question 17

Regarding the pharmacology of the barbiturates (true or false):

Thiopental is the sulphur analogue of pentobarbital

Answer 17

True

Question 18

Regarding the pharmacology of the barbiturates (true or false):

All barbiturates are derived from barbituric acid

Answer 18

True

Question 19

Regarding the pharmacology of the barbiturates (true or false):

Thiopental is an oxybarbiturate

Answer 19

False. Thiopental is an thiobarbiturate. Methohexital is an oxybarbiturate.

Question 20

Regarding the pharmacology of the barbiturates (true or false):

Barbituric acid is a condensation product of urea and lactic acid

Answer 20

False. Barbituric acid is a condensation product of urea and malonic acid.

Question 21

Regarding the pharmacology of the barbiturates (true or false):

The water solubility of barbiturates increases on transformation from the keto to enol form, called tautomerism

Answer 21

True

Question 22

Regarding the pharmacokinetics and mechanism of action of the barbiturates (true or false):

Thiopental has a pKa of 7.6 and a pH 10.5 in solution

Answer 22

True

Question 23

Regarding the pharmacokinetics and mechanism of action of the barbiturates (true or false):

Thiopental can undergo tautomerism from the enol to the keto form, which is more water-soluble

Answer 23

False. The enol form is more water-soluble in alkaline solutions.

Question 24

Regarding the pharmacokinetics and mechanism of action of the barbiturates (true or false):

Methohexital has a faster clearance than thiopental

Answer 24

True

Question 25

Regarding the pharmacokinetics and mechanism of action of the barbiturates (true or false):

Methohexital is 60% protein-bound, mainly in albumin

Answer 25

True

Question 26

Regarding the pharmacokinetics and mechanism of action of the barbiturates (true or false):

Barbiturates suppress the action of GABA

Answer 26

False. Barbiturates enhance the action of GABA by direct receptor binding and augmentation.

Question 27

Regarding the clinical uses of thiopental, methohexital and phenobarbital (true or false):

Thiopental is used for the induction of anaesthesia at a dose of 1-2 mg/kg

Answer 27

False. The dose of thiopental for induction is 3-7 mg/kg. Methohexital has an induction dose of 1-2 mg/kg.

Question 28

Regarding the clinical uses of thiopental, methohexital and phenobarbital (true or false):

Thiopental, methohexital and phenobarbital are used to treat status epilepticus

Answer 28

False. Methohexital is not used to treat status.

Question 29

Regarding the clinical uses of thiopental, methohexital and phenobarbital (true or false):

Phenobarbital can precipitate seizures and is used for anaesthesia in ECT

Answer 29

False. Methohexital is used in ECT.

Question 30

Regarding the clinical uses of thiopental, methohexital and phenobarbital (true or false):

Thiopental elicits a smooth induction with a clear endpoint and is often used for RSI

Answer 30

True

Question 31

Regarding the clinical uses of thiopental, methohexital and phenobarbital (true or false):

Methohexital is ultra-short acting and has an emerging role in pre-hospital care

Answer 31

True

Question 32

Regarding the clinical effects of thiopental, methohexital and phenobarbital (true or false):

Methohexital does not cause pain on injection

Answer 32

False. Methohexital can often cause pain on injection. However, this can be alleviated by mixing with 1% lidocaine.

Question 33

Regarding the clinical effects of thiopental, methohexital and phenobarbital (true or false):

Thiopental may elicit laryngospasm and bronchospasm on induction

Answer 33

True. Thiopental may elicit laryngospasm and bronchospasm on induction, thereby creating a difficult environment for placement of a supraglottic airway.

Question 34

Regarding the clinical effects of thiopental, methohexital and phenobarbital (true or false):

Thiopental can cause osteomalacia and hypersensitivity reactions

Answer 34

False. Phenobarbital is known to cause osteomalacia. Phenobarbital and thiopental have a risk of hypersensitivity reactions.

Question 35

Regarding the clinical effects of thiopental, methohexital and phenobarbital (true or false):

Thiopental and methohexital cause a decrease in mean arterial blood pressure on induction

Answer 35

True. Thiopental and methohexital both cause a decrease in mean arterial blood pressure on induction, thiopental to a greater extent.

Question 36

Regarding the clinical effects of thiopental, methohexital and phenobarbital (true or false):

Phenobarbital reduces intraocular pressure

Answer 36

False. Thiopental reduces intraocular pressure.