Peptic Ulcers & Reflux: Attack, Defence, and the Two Real Culprits
A peptic ulcer isn't just 'too much acid' — it's the balance between acid attacking the lining and mucus defending it, tipped the wrong way. And for most ulcers there are just two real causes to blame. Understanding attack-versus-defence tells you why we both suppress acid AND, in some cases, boost the stomach's own protection.
From the foundations article, remember that the stomach is a battleground between attack (acid) and defence (the protective mucus-bicarbonate layer). A peptic ulcer — a raw sore in the lining of the stomach or duodenum — develops when this balance breaks down and acid gets through to damage the tissue. Crucially, for the great majority of ulcers, that breakdown has one of just two causes: infection with a bacterium called Helicobacter pylori, or the use of anti-inflammatory painkillers (NSAIDs). Recognising these two culprits is the single most important step, because treating an ulcer means not just healing it but removing the cause. Alongside ulcers sits gastro-oesophageal reflux disease (GERD) — acid escaping upward into the oesophagus, causing heartburn — which shares much of the same drug approach.
The two culprits — and why NSAIDs cause ulcers
H. pylori and NSAIDs cause most ulcers — each by weakening defence. The two big causes both work by weakening the stomach's defences, not just by raising acid. H. pylori is a bacterium that lives in the stomach lining and damages the protective barrier, promoting ulcers (and it's important because eradicating it cures the ulcer and stops it coming back — the subject of the next article). NSAIDs (like ibuprofen, from the anti-inflammatory drugs) cause ulcers by a mechanism worth understanding: they block an enzyme (COX) that, among other things, produces the prostaglandins which maintain the stomach's protective mucus and blood flow. Take away those protective prostaglandins and the lining becomes vulnerable to acid — which is why long-term NSAID users are at real risk of ulcers and bleeding, and why they're often given a PPI alongside to protect the stomach. So the management of an ulcer has two parts: reduce the acid attack (with a PPI, which heals ulcers reliably), AND remove or counter the cause — eradicate H. pylori if present, and stop the NSAID if possible. Treating the acid without addressing the cause lets the ulcer return.
Cytoprotection: boosting the defence
Most of the time we treat acid disease from the attack side — suppressing acid with a PPI. But there's a second, elegant strategy: strengthen the defence instead. These 'cytoprotective' drugs work not by reducing acid but by reinforcing the stomach's own protective barrier. Misoprostol is the clearest example: it's a synthetic prostaglandin, so it directly replaces the very protective prostaglandins that NSAIDs deplete — which makes it specifically useful for preventing NSAID-induced ulcers (though it can cause diarrhoea, and importantly must be avoided in pregnancy because it stimulates the uterus). Sucralfate forms a physical protective coating over an ulcer, shielding it from acid so it can heal, like a bandage on a sore. Bismuth compounds coat the ulcer, have some activity against H. pylori, and appear in some eradication regimens. These defence-boosting drugs are used in specific situations rather than as first-line, but they complete the picture of the attack-defence balance: you can help the stomach either by turning down the acid, or by shoring up its protection. The two big everyday lessons, though, remain simple — for any ulcer, think of the two culprits (H. pylori and NSAIDs), and remember that a PPI both heals ulcers and protects the stomach of someone who must keep taking an NSAID.
- A peptic ulcer = the acid-attack vs mucosal-defence balance breaking down.
- Two main causes: H. pylori infection and NSAIDs — always identify and address the cause.
- NSAIDs cause ulcers by blocking protective prostaglandins (via COX) — give a PPI to protect at-risk users.
- A PPI both heals ulcers and controls GERD (acid reflux causing heartburn).
- Cytoprotectants boost defence: misoprostol (prostaglandin, avoid in pregnancy), sucralfate (coating), bismuth.
The most elegant link in this whole topic is why NSAIDs cause ulcers, because it connects the anti-inflammatory drugs to the stomach through one molecule: prostaglandins. NSAIDs relieve pain by blocking COX and cutting prostaglandin production — but prostaglandins aren't only about inflammation; in the stomach they maintain the protective mucus and blood flow. So the very action that eases a headache also strips the stomach of its defence, exposing it to acid. This immediately explains two things: why long-term NSAID users get ulcers, and why misoprostol — a synthetic prostaglandin — specifically prevents them, by replacing exactly what the NSAID removed. One molecule, prostaglandin, ties together pain relief, ulcer risk, and the drug that protects against it. See that connection and this topic stops being a list and becomes a story.
- Treating an ulcer's acid without finding/addressing the cause (H. pylori or NSAID) — it recurs.
- Not giving gastroprotection (a PPI) to a high-risk long-term NSAID user.
- Using misoprostol in pregnancy — it stimulates the uterus (contraindicated).
- Forgetting that NSAIDs harm the stomach by removing protective prostaglandins, not just by acid.
What are the two main causes of peptic ulcers?
- A peptic ulcer is the acid-attack vs mucosal-defence balance breaking down.
- Two main causes: H. pylori and NSAIDs — always identify and treat the cause, not just the acid.
- NSAIDs remove protective prostaglandins (via COX); give a PPI to protect at-risk users.
- Cytoprotectants boost defence: misoprostol (avoid in pregnancy), sucralfate, bismuth.
- Katzung BG. Basic & Clinical Pharmacology — Drugs Used in Acid-Peptic Diseases (mucosal protective agents).
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Peptic ulcer & mucosal protection.
- NICE / ACG — Peptic ulcer disease & NSAID gastroprotection guidelines.
- Whalen K. Lippincott Illustrated Reviews: Pharmacology — Mucosal protective agents.
