Pharmacology
Why NSAIDs cause peptic ulcers
NSAIDs (non-steroidal anti-inflammatory drugs) block cyclo-oxygenase (COX), the enzyme that makes the prostaglandins (local chemical messengers) protecting the stomach lining, so acid can then injure it.
Remember
Peptic ulcers from NSAIDs come mainly from blocking COX, which lowers the prostaglandins and so reduces the mucus, bicarbonate and blood flow that protect the stomach lining, rather than from simply adding acid.
Prostaglandins (local chemical messengers) are made by the enzyme cyclo-oxygenase, or COX. In the stomach lining (the gastric mucosa), they work like bodyguards. They stimulate the secretion of mucus and bicarbonate (an alkali that neutralises acid at the surface of the lining), keep blood flowing through the mucosa, and help to limit acid secretion.
In the stomach, the protective prostaglandins come from COX-1, which is constitutive, meaning it is switched on all the time as a housekeeping enzyme. COX-2 is mainly inducible, meaning it is switched on at sites of inflammation, and blocking it gives most of the pain relief. A non-selective NSAID such as ibuprofen blocks both forms, so the benefit and the stomach risk arrive together.
When prostaglandin levels fall, the lining has less mucus, less bicarbonate and a poorer blood supply, so it is more easily damaged by acid. Gastritis (inflammation of the stomach lining) can follow, and then a peptic ulcer, an open sore in the lining of the stomach or the first part of the duodenum. Ulcers can bleed or perforate (burst through the wall). The main problem is a weakened defence rather than a large rise in acid.
NSAIDs increase the risk of peptic ulceration (ulcers in the stomach or duodenum) roughly fourfold. The risk is higher in older people, with prolonged use, after a previous ulcer, and with corticosteroids (steroid drugs such as prednisolone) or with anticoagulants or an antiplatelet drug (one that reduces platelet clumping), such as low-dose aspirin. When an NSAID is unavoidable in a high-risk patient, a proton pump inhibitor (a drug that switches off the acid pumps in the stomach) is co-prescribed (given alongside it). Helicobacter pylori, a stomach bacterium, is a separate cause of ulcers.
Memory aid
prostaglandins are the stomach's bodyguards, and an NSAID sends the bodyguards home while the acid stays on duty
Picture the prostaglandins as bodyguards for the stomach lining, which an NSAID sends away while the acid carries on.
Key facts
- Target
- COX inhibition by NSAIDs lowers prostaglandins.
- Protective job
- Stomach prostaglandins support mucus, bicarbonate and mucosal blood flow, and they also help to limit acid secretion.
- Main form involved
- Most of the gastrointestinal side effects come from blocking COX-1.
- Size of risk
- NSAIDs raise the risk of peptic ulceration roughly fourfold.
- Warning signs
- Epigastric pain (felt in the upper middle abdomen) can signal an NSAID ulcer, and black stools or vomiting blood in a person taking an NSAID are warning signs of a bleeding ulcer.
- Protection
- A proton pump inhibitor is co-prescribed when an NSAID is unavoidable and the gastrointestinal risk is high.
- Safer for the stomach
- Selective COX-2 inhibitors, which spare most COX-1 activity, carry a lower gastrointestinal risk, though not zero.
Exam traps
- NSAIDs do not increase prostaglandin production. They block the COX enzymes, so production falls, and the lining becomes vulnerable because the prostaglandin protection is lost.
- NSAIDs do not directly stimulate Helicobacter pylori. The infection is a separate cause of ulcers, and the two are independent risk factors.
- Reduced platelet aggregation (clumping) is a genuine NSAID action and can make an existing ulcer bleed more, but platelets do not build the mucosal barrier, so it does not explain why the ulcer forms.
- Paracetamol is a common painkiller for period pain, but it is not an NSAID, so it does not strip the stomach lining of its protection.
- Blocking COX-2 where inflammation switches it on gives most of the pain relief. That describes the benefit, not the stomach damage.
Read the full notes
Tested in 14 SimpleMed+ questions
Practise it in Pharmacology, with the answer and a full explanation after every question.
Practise these questions