Lactulose

Question 1

What is the drug usually used for?

Answer 1

Constipation

Hepatic encephalopathy (portal systemic encephalopathy)

Question 2

Describe the pharmacodynamics of this drug

Answer 2

An osmotic laxative.

It is a synthetic derivative of lactose.

Broken down by intestinal bacteria into metabolites (e.g. methane) that promotes gut motility and increases the water cotent of the stool.

The lactic acid formed by its breakdown makes the colon more acidic and this helps ammonia in the bloodstream to diffuse into the colon.

Additionally the increased acidity of the colon helps to eliminate urease-producing bacteria, which contribute to the formation of ammonia.

Question 3

Describe the pharmacokinetics of this drug

Answer 3

Bioavailability = not absorbed (reaches colon relatively unchanged)

Volume of distribution = negligible as lactulose stays mainly in the GI tract

Metabolism = colon (via saccharolytic bacteria)

Excretion = faeces, kidney

Question 4

What are the contraindications of this drug?

Answer 4

Galactosaemia

GI obstruction

GI perforation/risk of GI perforation

Question 5

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

Answer 5

The common side effects are

• abdominal pain
• diarrhoea/flatulence
• vomiting

An uncommon side effect is electrolyte imbalance

Question 6

Is any monitoring required?

Answer 6

No

Question 7

What are the most clinically significant drug interactions?

Answer 7

May increase the loss of K+ induced by other drugs (e.g. thiazide diuretics, steriods, amphotericin B)

Concomitant use of cardiac glycosides can increase the effect of the glycosides through potassium deficiency

Increasing dosage = decrease of pH-value in the colon. Therefore drugs which are released in the colon pHdependently (e.g. 5-ASA) can be inactivated.