Chlordiazepoxide

Question 1

What is this chlordiazepoxide used to treat?

Answer 1

Alcohol withdrawal syndrome

Anxiety (short-term use)

NOTE: also known as “Librium”

Question 2

Describe the pharmacodynamics of this drug

Answer 2

GABA(A) receptor agonist (alcohol is also an agonist of the GABA(A) receptor)

Enhances GABA-mediate Cl- influx, through the GABA receptor channel into the neuron

This causes the repolarisation of the neuron

Inhibits AP

Question 3

Which class of drugs does chlordiazepoxide fall under?

Answer 3

Benzodiazepenes

Question 4

Describe the pharmacokinetics of this drug

Answer 4

Half life = 24-48 hours (the active metabolite)

Metabolised by the liver

Excreted via kidney in urine (1-2% unchanged and 3-6% unconjugated)

Question 5

What are the contraindications for chlordiazepoxide?

Answer 5

Chronic psychosis

Respiratory depression

Acute pulmonary insufficiency

Avoid using in pregnancy (can be teratogenic especially within the 1st trimester)

Question 6

What are most clinically significant (common and/or potentially life threatening) side effects of the drug?

Answer 6

Movement disorders

Increased risk of fall/abnormal gait (frequency unknown but significant especialy for elderly patients)

Menstrual disorder

Leucopenia/agranulocytosis (rare/very rare)

Question 7

What are the most significant drug interactions?

Answer 7

Alcohol + benzodiazepenes = enhanced sedative effects

Chlordiazepoxide + Phenytoin/Fosphenytoin = affects [phenytoin/fosphenytoin]

Cimetidine (H2 receptor antagonists for GORD treatment), omeprazole (PPI for GORD treatment) and disulfiram (acetyladehyde dehydrogenase inhibitor used to produce acute sensitivity to alcohol) reduce [chlordiazepoxide]