22.9 — Gut Drugs

Proton pump inhibitors are among the most prescribed drugs in the world, and a large fraction of people taking them have been on them for years with nobody ever asking whether they still need to be.

They are excellent drugs. They heal ulcers, they prevent bleeding in people at risk, and they control reflux that would otherwise damage the oesophagus.

They are also the clearest example in medicine of a treatment that starts for a good reason, continues by default, and never gets reviewed.

Acid suppression

Antacids and alginates

The simplest thing in the medicine cabinet: a base that neutralises acid by direct chemistry.

Calcium carbonate, magnesium hydroxide, aluminium hydroxide.

They work within minutes and last an hour or two, which makes them ideal for occasional heartburn and useless for anything sustained.

Magnesium salts loosen the bowels; aluminium salts constipate — which is why most products combine them, so the two effects cancel.

Alginates — the alginic acid in products such as Gaviscon — do something different. They form a gel raft that floats on top of the stomach contents, so what refluxes into the oesophagus is the raft rather than the acid. Taken after meals and at bedtime, which is when reflux happens.

And they interfere with the absorption of other drugs, so a two-hour gap is the general rule (Chapter 22.2).

H2 blockers

Famotidine, ranitidine, cimetidine.

Histamine is one of the signals that tells the stomach's parietal cells to produce acid. Blocking the H2 receptor reduces that signal.

Onset within an hour, lasting several hours. Weaker than proton pump inhibitors and faster.

Ranitidine was withdrawn worldwide in 2019 to 2020 after contamination with a probable carcinogen was found; famotidine replaced it.

Tolerance develops within weeks, which limits long-term use.

Proton pump inhibitors

Omeprazole, lansoprazole, pantoprazole, esomeprazole — the "-prazoles".

They block the proton pump itself, the final common step (Chapter 9.2) — the enzyme that physically pushes hydrogen ions into the stomach.

Whatever signal arrives — histamine, acetylcholine, gastrin — the pump is disabled, so acid production falls by 90 percent or more.

Two practical facts follow from how they work:

They take 3 to 5 days to reach full effect, because they only bind pumps that are actively working, and the stomach continuously makes new ones.

They work best taken 30 to 60 minutes before a meal, because the meal activates the pumps and the drug binds active pumps. Taken at bedtime on an empty stomach, they are far less effective — and this is one of the most common ways people get less benefit than they should.

Used for: reflux, ulcers, H. pylori eradication, protection alongside NSAIDs, and Barrett's oesophagus (Chapter 21.2).

Long-term concerns, stated in proportion:

Reduced B12 absorption over years, because acid is needed to release B12 from food protein.

Reduced magnesium, occasionally significant.

A modest increase in gut infections including C. difficile, because stomach acid is a barrier (Chapter 22.6).

Possible small effects on fracture risk and on kidney function.

Most of these associations are weak and observational, and the drugs are frequently taken by people who are unwell for other reasons, which confounds everything.

The sensible position: excellent drugs, used at the lowest effective dose, reviewed annually to see whether they are still needed. Not a reason for fear, and not a reason to take one indefinitely without thinking about it.

And stopping produces rebound acid, because the stomach has increased its gastrin drive. Step down gradually rather than stopping abruptly, which is why people who try to stop often conclude they cannot manage without them.

Laxatives

Four kinds, working four ways, and matching them to the problem is most of the skill.

Bulk-forming — ispaghula husk, methylcellulose. Fibre that holds water and increases stool volume, which stimulates the bowel to move it along.

They must be taken with plenty of fluid, and without it they can make things worse or, rarely, cause obstruction. Take days to work.

Osmotic — macrogol (polyethylene glycol), lactulose, magnesium salts.

They draw water into the bowel by osmosis, softening the stool.

Macrogol is the best-evidenced first choice for most constipation, and it works within a day or two.

Lactulose is a sugar we cannot digest; bacteria ferment it, which produces gas and bloating in many people — and that same fermentation is why it is used in liver disease, because it acidifies the colon and traps ammonia (Chapter 21.2).

Stimulant — senna, bisacodyl, sodium picosulfate. They stimulate the nerves in the bowel wall directly, working in 6 to 12 hours.

Useful, and not for indefinite daily use without a reason — though the old claim that they cause a permanently "lazy bowel" is weaker than it was long presented as, and they are used long term in opioid-induced constipation with good reason.

Softeners and lubricants — docusate, glycerol suppositories, arachis oil enemas.

Choosing: hard stool needs softening — macrogol. Soft stool that will not move needs stimulating — senna. Opioid constipation needs both, started at the same time as the opioid (Chapter 22.5).

And the specific drugs for opioid constipation — naloxegol, methylnaltrexone — block opioid receptors in the gut only, without reversing the pain relief, which is an elegant solution to a very common problem.

The non-drug measures are real: fluid, fibre, activity, and not ignoring the urge. And a footstool that raises the knees above the hips changes the angle of the rectum and genuinely makes defecation easier — a small, physical, well-founded intervention.

Red flags with new constipation: over 50 with a change in bowel habit, blood in the stool, weight loss, anaemia, or a family history of bowel cancer. Those need investigating rather than treating.

Antidiarrhoeals

Loperamide — an opioid that acts on the gut and barely crosses into the brain, so it slows transit without causing opioid effects centrally.

Useful for symptom control in ordinary diarrhoea.

And not used when: there is high fever or blood in the stool, because slowing the gut can prolong bacterial infections and, in some, precipitate severe complications; or in suspected C. difficile.

And a warning worth including: loperamide has been taken in very high doses recreationally, and it causes fatal heart rhythm disturbances at those doses. At normal doses it is safe.

Oral rehydration solution is the actual treatment for diarrhoea, and it is the more important item.

The mechanism is one of the most valuable pieces of physiology ever applied: glucose and sodium are absorbed together by a shared transporter in the small intestine, and that transporter keeps working even when the gut is inflamed (Chapter 9.3). So adding glucose to salt water drives absorption of both, and water follows.

This is why the ratio matters and why plain water or fizzy drinks do not work as well. Oral rehydration therapy is estimated to have saved tens of millions of lives, mostly children, and it costs almost nothing.

Racecadotril, where available, reduces secretion rather than slowing motility.

Anti-sickness drugs

And the useful thing here is that different causes of nausea use different receptors, so matching the drug to the cause works far better than picking one at random.

Cause	Best choice
Motion sickness	Hyoscine, cyclizine
Vertigo, inner ear	Prochlorperazine, cinnarizine
Chemotherapy	Ondansetron, aprepitant
Post-operative	Ondansetron, dexamethasone
Drugs, metabolic causes	Haloperidol, metoclopramide
Slow stomach emptying	Metoclopramide, domperidone
Pregnancy	Doxylamine with B6, cyclizine

Ondansetron blocks serotonin 5-HT3 receptors, in the gut and in the brain's vomiting centre. Very effective, and causes constipation and QT prolongation.

Metoclopramide speeds stomach emptying and blocks dopamine receptors.

And it carries a specific hazard: dystonic reactions — sudden involuntary muscle spasms of the neck, jaw or eyes, frightening and more common in young people. Reversed with an anticholinergic. Which is why its use is limited to short courses.

And it must be avoided in Parkinson's disease, along with prochlorperazine, because both block dopamine and will worsen the condition markedly (Chapter 20.3). Domperidone and ondansetron are the safe alternatives, and this is one of the more useful drug-safety facts in the book.

Cyclizine — an antihistamine, sedating, and widely used.

Hyoscine — anticholinergic, for motion sickness, available as a patch.

Dexamethasone — surprisingly effective as an add-on, mechanism not fully explained.

Drugs for inflammatory bowel disease

Aminosalicylates — mesalazine, for ulcerative colitis. Formulated to release in the colon.

Steroids for flares, not for maintenance.

Immunomodulators — azathioprine, mercaptopurine. Requiring blood monitoring, and TPMT enzyme testing before starting, because people with low enzyme activity suffer severe bone marrow suppression — a clean example of pharmacogenomic testing in routine practice (Chapter 22.1).

Biologics — anti-TNF and newer targeted agents, which changed outcomes substantially (Chapter 21.2).

The rest of the cabinet

Antispasmodics — hyoscine butylbromide, mebeverine, peppermint oil. For cramping pain in irritable bowel syndrome.

Ursodeoxycholic acid — for certain liver conditions and some gallstones.

Pancreatic enzyme replacement — for pancreatic insufficiency (Chapter 21.2). Taken with every meal and snack, because it has to mix with the food to work at all.

Rifaximin — a non-absorbed antibiotic, used in hepatic encephalopathy and in some cases of irritable bowel syndrome.

Probiotics — the honest assessment is that the evidence is strain-specific and inconsistent. Reasonable evidence for preventing antibiotic-associated diarrhoea and for some infant conditions; weak or absent evidence for most of what they are sold for. A product labelled "probiotic" tells you almost nothing without knowing the specific strain and dose that was studied.

The practical summary

Take proton pump inhibitors before food, and review whether you still need them once a year.

Match the laxative to the stool — soften what is hard, stimulate what will not move.

Oral rehydration solution matters more than an antidiarrhoeal.

Match the anti-sickness drug to the cause.

And in Parkinson's disease, avoid metoclopramide and prochlorperazine.

What the next page fixes

Chapter 22.10 covers respiratory drugs — inhalers, what each colour actually does, and why technique matters more than the prescription.