Gastro-Oesophageal Reflux Disease

Risk Factors and Aetiology

Risk factors for GORD include pregnancy, hiatus hernia, family history, stress, smoking, alcohol consumption, consumption of fatty or spicy foods, and certain medications.

Medications that can contribute to GORD include:

• Alpha blockers
• Anticholinergics
• Benzodiazepines
• Beta blockers
• Bisphosphonates
• Calcium channel blockers
• Corticosteroids
• NSAIDs
• Doxycycline
• SSRIs

Peptic ulcer disease (PUD) can co-exist with GORD and possesses many of the same risk factors. PUD involves ulceration of the gastric or duodenal mucosa – a breach in the epithelial lining and is most commonly caused by Helicobacter pylori (H. pylori) infection, but also by NSAID use, smoking, and alcohol intake.

Diagnosis of H.Pylori can be confirmed through testing (e.g. urea breath test, stool antigen),and should be followed by eradication treatment involving triple therapy: a proton pump inhibitor (PPI) and two antibiotics (typically amoxicillin, clarithromycin, or metronidazole).

Lifestyle Modifications

The following lifestyle modifications should be advised for all patients:

• Reduce alcohol and smoking
• Minimise stress
• Review medications that may aggravate symptoms
• Eat smaller meals and avoid eating within 3–4 hours of bedtime
• Elevate the head of the bed (not just with pillows—use bricks or blocks to raise the bedhead by 10–20 cm

Antacids and Alginates

For mild dyspepsia, antacids and alginates may be appropriate:

• Antacids (e.g. Rennie chewable tablets) raise gastric pH.
  • Aluminium-containing antacids can cause constipation
  • Magnesium-containing antacids can cause diarrhoea
• Alginates (e.g. Peptac, Gaviscon) form a viscous ‘raft’ that floats on gastric contents to reduce reflux.

Caution: Gaviscon Liquid contains high sodium content (12.4 mmol per 20 mL dose, approximately 14.26% of WHO’s recommended daily sodium intake). Use caution in patients on sodium-restricted diets, such as those with heart failure or renal impairment.

Proton Pump Inhibitors (PPIs)

PPIs are the mainstay of treatment for:

• GORD
• Oesophagitis
• Peptic ulcer disease
• Dyspepsia

Examples include omeprazole and lansoprazole.

PPIs inhibit the H⁺/K⁺-ATPase enzyme (proton pump) in gastric parietal cells – this blocks the final step of acid production, reducing both basal and stimulated acid secretion. PPIs are acid-labile, so oral formulations are enteric-coated to protect the drug from degradation in the stomach. Absorption generally occurs in the small intestine.

Adverse Effects

Hyponatraemia is a commonly cited adverse effect, however it should be noted that this is a rare occurrence and other factors contributing towards hyponatraemia should be investigated. However, hypomagnesaemia has been reported with long-term use (MHRA Drug Safety Update, 2014), and it is recommended to monitor serum magnesium in at-risk patients (e.g. on diuretics or digoxin).

Other adverse effects include the following:

• Fracture risk (hip, wrist, spine) with long-term use (>1 year), particularly in elderly patients or those with other risk factors
• Increased risk of GI infections, including Clostridium difficile

Drug Interactions

Some drug interactions arise due to the change in gastric pH:

Reduced absorption of drugs that require acidic pH

• Ketoconazole, itraconazole, atazanavir, nelfinavir

Increased absorption of drugs that favour a more alkaline pH

• Increased PERT (pancreatic enzyme replacement therapy) absorption due to increased gastric pH—this interaction is clinically useful to increase efficacy of PERT when co-administered with a PPI

Other relevant interactions include the following:

• Reduced vitamin B₁₂ absorption with long-term use
• Omeprazole inhibits CYP2C19, which can reduce activation of clopidogrel (a prodrug metabolised by CYP2C19), potentially decreasing its antiplatelet efficacy. While the clinical significance remains debated, consider using an alternative PPI (e.g. lansoprazole) when prescribing with clopidogrel.

H₂ Receptor Antagonists

H2 receptor antagonists such as famotidine can also be used to treat GORD and dyspepsia. H2 receptor antagonists work by blocking histamine receptors of the gastric parietal cells which stimulate gastric acid secretion. While effective, PPIs are generally preferred due to superior acid suppression.

Adverse Effects

Although uncommon, adverse effects include the following:

• Gynaecomastia
• Erectile dysfunction
• Leucopenia

Drug Interactions

H2 receptor antagonists also reduce gastric acid secretion, there is the potential for the same drug-drug interactions to be seen as with PPIs due to this effect.

Created in BioRender. Boucher, M. (2025) https://BioRender.com/g9gp37y

Fig 2: Mechanism of action of drugs for GORD

References

1. BNF online gastro-oesophageal reflux disease.available from: Gastro-oesophageal reflux disease summaries | BNF | NICE Accessed 13/8/24.
2. MHRA Proton pump inhibitors in long-term use: reports of hypomagnesaemia. Published 11/12/14. Available from: Proton pump inhibitors in long-term use: reports of hypomagnesaemia – GOV.UK (www.gov.uk)  Accessed 14/8/24.
3. SPC omeprazole 20mg capsules. Updated on emc: 25 Jul 2024. Available from: Omeprazole 20mg Capsules – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) Accessed 14/8/24.
4. Ranitidine – MHRA drug alert issued for Teva UK recall. Published 17 oct 2019. Available from: Ranitidine – MHRA drug alert issued for Teva UK recall – GOV.UK (www.gov.uk). Accessed 14/8/24.
5. SPC Famotidine. Last updated on emc: 11 Oct 2023. Available from: Famotidine 20mg Tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 14/8/24.
6. SPC Gaviscon peppermint liquid. Last updated on emc: 15 Jan 2024. Available from: Gaviscon Peppermint Liquid Relief – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk). Accessed 14/8/24.
7. BNF summary Peptic ulcer disease | Treatment summaries | BNF | NICE accessed 1/9/24
8. Eriksson S, Långström G, Rikner L, Carlsson R, Naesdal J (1995). “Omeprazole and H2-receptor antagonists in the acute treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis: a meta-analysis”. Eur J Gastroenterol Hepatol. 7 (5): 467–75. PMID 7614110.. A correction was published in European Journal of Gastroenterology & Hepatology 1996;8:192.