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Drugs Used in Gastroenterology

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Proton Pump Inhibitors

Overview

Proton pump inhibitors (PPIs) are a class of drugs that irreversibly bind to gastric parietal cells’ H+/K+ ATPase proton pumps leading to reduced stomach acid production. PPIs used in the UK are omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole.

Contraindications

PPIs should not be prescribed to patients with alarm symptoms (see Dyspepsia) before endoscopy and should be stopped for at least 2 weeks. This is because they may mask the symptoms of an upper gastrointestinal malignancy.

Adverse effects

Common adverse effects:

Features associated with long-term use:

Interactions

Clopidogrel:

  • Omeprazole and esomeprazole should be avoided as they can reduce the antiplatelet effect. Other PPIs may still have this effect, but to a lesser extent, and the risks and benefits should be weighed up

Protease inhibitors (typically drugs used in managing HIV):

  • PPIs can reduce the plasma levels of some protease inhibitor drugs

Aminosalicylates

Overview

Aminosalicylates used in the UK include mesalazine, sulfasalazine, balsalazide, and olsalazine. They are used in treating inflammatory conditions such as inflammatory bowel disease and rheumatic diseases such as rheumatoid arthritis.

Mechanism of action

Its mechanism is not fully understood but is thought to decrease the production of prostaglandins and pro-inflammatory cytokines.

Adverse effects

The general side effects of aminosalicylate drugs are:

  • Gastrointestinal discomfort
  • Nausea
  • Vomiting
  • Agranulocytosis
    • This can lead to increased vulnerability to infection
    • Any unwell patient (e.g. fever, sore throat etc.) taking immunosuppressants that risk agranulocytosis including aminosalicylates should have an immediate full blood count to rule out agranulocytosis
  • Pancreatitis (more common in mesalazine than sulfasalazine)

Sulfasalazine has additional adverse effects:

  • Oligospermia
  • Headaches
  • Insomnia
  • Skin rashes
  • Lung fibrosis

Laxatives

Overview

Laxatives are used to increase stool frequency or ease its passage by increasing stool water content or accelerating bowel transit. Laxatives can be divided into:

  • Bulk-forming laxatives – retain fluid in stool, soften stool, and increase peristalsis:
    • Ispaghula husk
    • Methylcellulose
    • Sterculia
  • Osmotic laxatives – increase fluid in the large bowel causing distention and stimulating peristalsis:
    • Lactulose – also softens stool
    • Macrogols (e.g. polyethene glycol) – also softens stool
    • Phosphate and sodium citrate enema
  • Stimulant laxatives – stimulate nerves to cause peristalsis:
    • Senna
    • Bisacodyl
    • Sodium picosulfate
    • Docusate
  • Pro-kinetic laxatives:
    • Prucalopride – serotonin (5-HT4) receptor agonist

Antidiarrhoeals

Overview

Most episodes of acute diarrhoea settle without the need for medical treatment. When rapid control of symptoms is required, or in cases of mild-moderate diarrhoea where toilet amenities are limited, antimotility agents may be used. They should be avoided in bloody diarrhoea due to inflammatory pathology.

The most commonly used antimotility agent used is loperamide, which is a mu-opioid agonist, which decreases peristalsis. It does not cross the blood-brain barrier at standard doses, and therefore does not usually have other effects associated with opioids (e.g. analgesia).

Pro-Kinetics

Overview

Pro-kinetic drugs increase gastrointestinal (GI) motility and peristalsis and can be used to treat nausea and vomiting due to reduced gastric motility. Some indications include gastroparesis, gastro-oesophageal reflux disease, and nausea associated with acute migraine (as they can cause gastroparesis).

Metoclopramide

Metoclopramide is primarily a dopamine D2 receptor antagonist of the chemoreceptor trigger zone in the medulla, reducing nausea and vomiting. Its mechanism of action also includes 5-HT4 receptor agonist activity, which alongside the D2 receptor antagonism promotes GI motility.

Metoclopramide is contraindicated in:

  • 3-4 days after GI surgery
  • Epilepsy
  • Intestinal obstruction
  • GI perforation
  • Any scenario where increased GI motility would be harmful
  • Phaeochromocytoma

Metoclopramide should be used with caution in:

The adverse effects of metoclopramide include:

  • Extra-pyramidal side effects (common or very common) – more common in young people, with high doses, or long therapy:
    • Acute dystonia (e.g. oculogyric crises – prolonged involuntary upward deviation of the eyes)
    • Akathisia – restlessness
    • Tardive dyskinesia – involuntary muscle movements of the lower face and extremities
    • Parkinsonism (e.g. tremor, rigidity, bradykinesia, postural instability)
  • Diarrhoea (common or very common)
    • Occurs as it is a pro-kinetic
  • Depression (common or very common)
    • Due to dopamine inhibition
  • Hyperprolactinaemia and galactorrhoea (rare or very rare)

Domperidone

Like metoclopramide, domperidone is also primarily a D2 receptor antagonist, however, it does not cross the blood-brain barrier (BBB), reducing the likelihood of extrapyramidal side effects. It can still cause hyperprolactinaemia as the pituitary gland is outside of the BBB.

Domperidone is contraindicated in:

  • 3-4 days after GI surgery
  • Any condition impairing cardiac conduction
  • Domperidone is associated with QT prolongation
  • Intestinal obstruction
  • GI perforation
  • Any scenario where increased GI motility would be harmful
  • Prolactinoma

Domperidone should be used with caution in:

  • Patients >60 years due to the increased risks of QT prolongation and ventricular arrhythmia

The adverse effects of domperidone include:

  • Dry mouth (very common)
  • Palpitations (frequency not known)
  • Headaches (uncommon)
  • Diarrhoea (uncommon)
  • Hyperprolactinaemia (uncommon):
  • Gynaecomastia
  • Galactorrhoea

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