Barbiturates

Question 1

List several barbiturates.

Answer 1

Pentobarbitone, phenobarbitone, thiopentone, primidone

Question 2

Describe the mechanism of action of barbiturates.

Answer 2

CNS depression by enhancing GABA-mediated inhibitory neurotransmission. They bind GABA-A receptor complex and increase the duration of chloride channel opening. Also antagonises the effect of glutamate (excitatory). Inhibition of medullary cardiorespi centres/hypothalamic autonomic nuclei –> hypotension, hypothermia and respiratory arrest.

Question 3

What is the difference between barbiturates and benzodiazepines?

Answer 3

Barbiturates increase the duration of chloride channel opening by binding to the GABA-A receptor, benzos increase the frequency of their opening

Question 4

Describe what barbiturates can be given orally and which must be given IV.

Answer 4

Oral: less lipid soluble drugs such as phenobarbitone and primidone. Thiopentone and pentobarbitone only IV because highly lipid soluble, rapidly redistributes and large volume of distribution.

Question 5

How are barbiturates metabolised?

Answer 5

By saturable hepatic metabolism

Question 6

Discuss the metabolism of primidone.

Answer 6

First metabolised to phenobarbitone and PEMA

Question 7

Discuss the metabolism of phenobarbitone.

Answer 7

Undergoes both enterohepatic anc enteroenteric recirculation. 25-50% is excreted unchanged in the urine

Question 8

Describe the clinical features of barbiturate toxicity.

Answer 8

CNS: profound coma which mimics brainstem death, CVS: tachy, hypotension, Other: hypothermia, reduced bowel sounds, skin bullae - barbiturate blisters

Question 9

What can be said about the duration of barbiturate toxicity?

Answer 9

Short-acting (pentobarbitone): 24-48 hours. Long-acting (phenobarbitone, primidone): days/weeks due to saturable metabolism

Question 10

At what serum phenobarbitone level is coma requiring intubation expected?

Answer 10

> 80 mg/L

Question 11

At what serum phenobarbitone level should haemodialysis be considered?

Answer 11

> 100 mg/L

Question 12

Are there enhanced elimination strategies that can be considered with phenobarbitone toxicity? What?

Answer 12

MDAC - interrupts enterohepatic circulation, consider haemodialysis. Urinary alkalinisation is not recommended and is inferior to MDAC.

Question 13

What are the three unusual but eminently treatable causes for coma?

Answer 13

Carbamazepine, sodium valproate and barbiturates poisoning