Anti Diarrhoeal Agents

Question 1

Example of an anti diarrhoeal (antimobility) agent

Answer 1

Loperamide

Question 2

How does Loperamide work?

Answer 2

Loperamide is an opioid similar to pethidine. However, unlike pethidine, is does not penetrate the CNS so has no analgesic effects.

It is an agonist of the opioid µ-receptors in the gastrointestinal tract. This increases non-propulsive contractions of the gut smooth muscle but reduces propulsive (peristaltic) contractions. As a result, transit of bowel contents is slowed and anal sphincter tone is increased. Slower gut transit also allows more time for water absorption, which (in the context of watery diarrhoea) has a desirable effect in hardening the stool.

Question 3

Indications of Loperamide

Answer 3

Diarrhoea: symptomatic in the context of irritable bowel syndrome or viral gastroenteritis.

Question 4

Contraindications of Loperamide

Answer 4

Loperamide should be avoided in acute ulcerative colitis where inhibition of peristalsis may increase the risk of megacolon and perforation.

For the same reason, it should be avoided where there is a possibility of Clostridium difficile colitis, including in patients who develop diarrhoea in association with broad-spectrum antibiotic use.

It should not be used in acute bloody diarrhoea (dysentery) because this may signify bacterial infection.
Particularly worrying in this context is Escherichia coli, as certain strains of this can cause a serious condition called haemolytic–uraemic syndrome (HUS). Use of antimotility drugs appears to increase the risk of HUS.

Question 5

Possible interactions of Loperamide

Answer 5

No clinically significant interactions

Question 6

Elimination of Loperamide

Answer 6

Oxidative N-demethylation by CYP450 isozymes, CYP2C8 and CYP3A4,

Question 7

Patient information of Loperamide

Answer 7

Patients who have to pay for their prescriptions will probably save money if they buy it over the counter rather than on prescription.

In acute ‘simple’ diarrhoea, the usual dose is 4 mg, followed by 2 mg with each loose stool, generally to a maximum of 8 mg (4 tablets) per day.
Loperamide is usually taken as a capsule or tablet. A syrup form is available, which may be useful in children (over 4 years old) with acute viral gastroenteritis.

You should ensure your patient is aware that the only purpose of loperamide is to help settle the diarrhoea. It does nothing for the underlying cause. Make sure they know to stop taking it if they develop constipation, abdominal pain, or (in acute diarrhoea) they find they need to take it for more than 5 days.

Question 8

Side effects of Loperamide

Answer 8

In itself, loperamide is a safe drug with few adverse effects. These are mostly gastrointestinal effects predictable from its mechanism of action (e.g. constipation, abdominal cramping and flatulence). Indirectly, adverse effects may arise from the inappropriate inhibition of peristalsis (see Warnings). Where CNS-penetrating opioids are used (e.g. codeine phosphate), there is a risk of opioid toxicity and dependence (see Opioids, weak