Steroids are not dangerous in themselves — how much and for how long is what does the damage. At replacement doses you see none of this, and even a big dose for a few days usually causes nothing.

What goes wrong with prolonged use: thinning bones that fracture (ribs and spine especially — sometimes within weeks on high doses), infections, fluid and salt problems, mood changes, cataracts and glaucoma, ulcers, and the puffy Cushing appearance. Bone loss is mostly a problem with tablets or injections — inhalers and creams rarely cause it, even long term.

The most dangerous one is adrenal suppression. Taking steroids tells the body to stop making its own, and eventually the adrenal glands shrink.

• Recovery takes anywhere from 5 days to a year.
• What decides that is how LONG they took it, not how much — which is the opposite of what most people assume.

This matters most in a crisis. Normally the adrenals pour out extra steroid during trauma or surgery, and that surge keeps people alive. Someone suppressed cannot do it — so give them MORE steroid when they are ill or having surgery, not less, and keep giving top-up doses for a while even after they stop.

• With digoxin — steroids lower potassium, and low potassium makes digoxin dangerous.
• With thiazide or loop water tablets — those lower potassium too, so it compounds.
• With NSAIDs — both irritate the gut, so ulcers and bleeding become much likelier.

Never give them to someone with a fungal infection through the body, or to anyone having a live vaccine.

Outside hormone replacement, steroids are used for rheumatoid arthritis, lupus, inflammatory bowel disease, allergies, asthma and skin conditions.

DMARD stands for disease-modifying antirheumatic drug, and the name is the point: these are the only ones that actually slow the disease down and stop joints being destroyed. They do it by interfering with the immune and inflammatory response.

Three kinds:

• Conventional ones are small molecules made by ordinary chemistry, and they affect the immune system broadly — methotrexate is the main one.
• Biologic ones are large molecules grown using DNA technology, and they target cytokines — the TNF inhibitors like adalimumab and etanercept.
• Targeted ones are the newest: small synthetic molecules aimed at one specific thing, such as the JAK inhibitors.

How the three treatment groups compare is the thing worth being clear about:

• NSAIDs relieve symptoms quickly but do nothing to stop the joints being damaged. They are the safest, so they need less monitoring.
• Steroids relieve symptoms quickly and do slow the disease — but they are too toxic long term, so they are used in short bursts.
• DMARDs are the ones that protect the joints.

Start a DMARD within 3 months of diagnosis. Started early enough, they can delay or even prevent serious joint damage — which is why rheumatoid arthritis is not treated by simply increasing painkillers.

Methotrexate is the first DMARD to reach for — it works, it is comparatively safe, and it is cheap. At least 8 in 10 people improve, and it acts faster than any other DMARD, in 3 to 6 weeks.

It blocks folate, which cells need to copy their DNA. In cancer that is clearly how it works; in rheumatoid arthritis the textbook admits the mechanism is not really understood, though it seems to come from damping down B and T lymphocytes.

Everyday side effects: nausea, vomiting, diarrhoea, headache, tiredness — and a cough or breathing symptoms even when there is no infection.

The serious ones are different: liver scarring, bone marrow being shut down, ulcers in the gut, and inflammation of the lungs. So that cough is not something to wave away.

• Give folic acid, at least 5 mg a week, to protect the gut and liver. It does not cancel the drug out, because it drifts into cells passively instead of competing with methotrexate.
• Screen for TB before starting.
• Check blood count, liver and kidneys first, then keep checking them — that monitoring is not optional.

The single most important rule: get a DMARD started within 3 months of diagnosis. Do it early enough and you can delay or even prevent the joints being wrecked. Wait, and that chance is gone.

That is why rheumatoid arthritis is not treated by simply turning up the painkillers.

• NSAIDs make people feel better quickly and protect the joints not at all. They are the safest, so they need the least monitoring.
• Steroids also work quickly, and they do slow the disease — but they are too toxic to keep going, so they are used in short bursts.
• DMARDs are slower to work but they are what actually saves the joints.

Methotrexate is the one to start with — effective, comparatively safe, cheap, and quicker than any other DMARD at 3 to 6 weeks. Around 8 in 10 people improve on it.

If methotrexate is not enough, the other options are the biologics (large molecules that block cytokines, like the TNF inhibitors) and the newer targeted tablets such as the JAK inhibitors.

Two more things. DMARDs need the closest monitoring of the three — that is the price of the protection they give. And the biologics are more than the TNF inhibitors: rituximab, abatacept, and the IL-6 and IL-1 antagonists are all in that group.

Never give aspirin to someone with a peptic ulcer, a bleeding disorder such as haemophilia or vitamin K deficiency, or an allergy to aspirin or any other NSAID.

Never give any NSAID in the last three months of pregnancy — they can close the ductus arteriosus in the baby too early.

Be extremely careful in pregnancy generally, and in a child who has chickenpox or flu.

Ordinary caution covers a long list: older people, smokers, H. pylori infection, heart failure, cirrhosis, low blood volume, poor kidneys, asthma, hay fever, chronic hives, nasal polyps, and a history of problem drinking.

Stop aspirin a week before planned surgery, or a week before the due date.

And the paediatric rule everyone knows: because of Reye syndrome, no aspirin for infants, children or teenagers. Use paracetamol or ibuprofen for their fever instead.

Meloxicam is an ordinary older-style NSAID — it blocks both COX-1 and COX-2 — with one unusual feature: it hangs around in the body for 15 to 20 hours. Most of its relatives clear in 2 to 7.

That is why it is taken once a day: one dose keeps working all day. The maximum is 15 mg daily, and it is approved for arthritis.

The non-aspirin NSAIDs as a group are mainly for rheumatoid arthritis and osteoarthritis, with some also used for fever, bursitis, tendinitis, moderate pain and period pain.

One thing not to assume: aspirin protects against heart attacks, and the other NSAIDs do not. That benefit belongs to aspirin alone.

Because it blocks COX-1 too, all the usual NSAID cautions apply — stomach, bleeding and kidneys.

The pain range is mild to moderate, not moderate alone.

There are two versions of this enzyme, and telling them apart explains every NSAID side effect you will ever be asked about.

• COX-1 is everywhere, doing maintenance: protecting the stomach lining, keeping the kidneys working, helping platelets clump.
• COX-2 appears where tissue is injured, and drives inflammation and pain. It is also in the brain, kidneys, blood vessels and colon.

So blocking COX-2 gives you the effect you wanted, and blocking COX-1 gives you the trouble.

The stomach part is worth knowing properly. COX-1 protects the stomach in three ways at once — less acid, more bicarbonate and protective mucus, and better blood flow under the lining. An NSAID knocks out all three together, which is why ulcers happen.

• The COX blockers that fight inflammation are the NSAIDs — aspirin, ibuprofen, naproxen, celecoxib.
• The one that does not fight inflammation is paracetamol/acetaminophen. It helps pain and fever only.
• Older NSAIDs block both COX-1 and COX-2, so you cannot get the benefit without the ulcer and kidney risk.
• Newer ones (coxibs) block only COX-2. In theory that should be safer — but the book says the opposite turned out to be true: they appear less safe overall, because they raise the risk of heart attack and stroke.

Taken for a few days for pain or fever, aspirin rarely does anything serious. The trouble comes from taking a lot of it for a long time, which is what treating inflammation requires.

• Most people just get indigestion, heartburn or nausea — less so if taken with food or a big glass of water.
• Slow, invisible bleeding from the gut is common. Barely anything on any one day, but over months it adds up to anaemia.
• Even a low dose, taken long enough, can cause an ulcer that perforates or bleeds dangerously.

There are four reasons the ulcers happen: more acid and pepsin, less protective mucus and bicarbonate, less blood flow under the lining, and the tablet physically irritating the stomach.

Three of those four are the drug's chemistry, not the tablet touching anything — they come from blocking COX-1. Only the last one is direct contact, and it is worst with tablets that dissolve slowly, because the gritty bits lodge in the folds of the stomach and sit there.

The frightening part: these ulcers often cause no symptoms at all. Someone can perforate or start bleeding heavily with no warning. Feeling fine is not evidence of being fine.

The thing to know about colchicine is that its role has changed. It used to be the standard treatment for an acute gout attack — even though, as the textbook says plainly, the risks never really justified the benefits.

Now it is a fallback. It is kept for people who cannot tolerate the safer drugs, or who did not respond to them.

• First choice for an attack: an NSAID.
• Also fine: a steroid.
• Colchicine: only if those are not options.

It sits in a category of its own — the antigout anti-inflammatory — separate from both the NSAIDs and the drugs that lower uric acid. There is also a combined tablet with probenecid, which puts the anti-inflammatory and the uric-acid-lowering effect together.

For preventing gout it is not recommended under 16. Note that limit is specifically about gout — it is used differently in familial Mediterranean fever.

The combination tablet is colchicine 0.5 mg with probenecid 500 mg — one a day for a week, then one twice a day.

Celecoxib is the newer kind of NSAID — it blocks only COX-2, leaving COX-1 alone. Up to 400 mg a day, and it lasts about 11 hours.

The idea was elegant. Older NSAIDs block both, so you cannot get pain relief without risking ulcers, bleeding and kidney damage. Block only COX-2 and you should get the benefit without the harm.

It did not work out that way. The textbook says plainly that the COX-2 drugs turned out to be less safe overall than the older ones, because they raise the risk of heart attack and stroke.

The reason is that COX in blood vessels makes prostacyclin, which keeps vessels relaxed. Block that and vessels stay tighter — and heart attacks and strokes follow.

So the honest summary is a swap, not an improvement: easier on the stomach, harder on the heart. "Newer" is not "safer" here.

The question that decides everything: how often does this person get attacks?

• Fewer than three a year — just treat the attacks when they happen. NSAIDs are first choice for the pain; steroids are also fine.
• Three or more a year, or chronic or tophaceous gout — now you also need to bring the uric acid level down.

Colchicine is no longer the go-to for an attack. It used to be, despite never having a good risk-to-benefit balance. Today it is kept for people who cannot take, or do not respond to, the safer options.

There are three ways to lower uric acid:

1. Make less of it — allopurinol, febuxostat.
2. Get rid of more of it — probenecid.
3. Turn it into something else the kidney can dump easily — pegloticase, rasburicase.

None of those five helps an attack that is happening now. They have no anti-inflammatory or painkilling effect at all. Starting allopurinol in the middle of a flare is answering a different question.

This all comes from the 2020 American College of Rheumatology guidelines.

"Uricosuric" describes what the drug does, not what it is called: it makes the kidneys get rid of more uric acid. Probenecid is the one.

There are three ways to bring uric acid down, and this is the middle one — make less (allopurinol, febuxostat), excrete more (probenecid), or convert it into something easier to pass (pegloticase, rasburicase).

• Start at 250 mg twice a day for a week, then settle on 500 mg twice a day.
• It peaks in 2 to 4 hours and lasts 6 to 12.
• Use a lower dose if the kidneys are impaired, since that is how it leaves the body.

It does nothing for an attack in progress — no painkilling, no anti-inflammatory effect. It is for people who keep getting gout, not for the person in pain in front of you today.

There is a combined tablet of colchicine and probenecid: one a day for a week, then twice a day.

A few more figures: 85–95% of a dose is absorbed, it is broken down by the liver and leaves in the urine, and the combination tablet is colchicine 0.5 mg with probenecid 500 mg. It has been given to children from age 2, for reasons other than gout.

Calcitonin does two things, and both of them bring calcium down:

1. It stops the cells that dissolve bone from working, so less calcium is released out of the skeleton.
2. It stops the kidney reabsorbing calcium, so more of it leaves in the urine.

Because bone turnover slows, the alkaline phosphatase in blood falls and hydroxyproline in urine rises — those are the signs it is working.

It is not a first-choice drug. The specialist guidelines say there are better options now, and you are meant to weigh its risks before reaching for it. It is still one of the body's three calcium regulators, alongside parathyroid hormone and vitamin D — it is just been overtaken as a treatment.

• Nasal spray: 200 IU — one spray — once a day, swapping nostrils each day.
• Injection: 100 IU every other day for osteoporosis after the menopause; 100 IU daily for Paget disease. Same dose whether into muscle or under the skin.

One more indication: by injection it is also used for hypercalcaemia, starting at 4 IU/kg.

Do not give calcium to someone who already has too much calcium in the blood, who forms kidney stones, or whose phosphate is low. In each case you would be feeding the problem.

There is a neat circularity here: taking calcium for a long time causes high blood calcium — the very thing that rules it out. So check the level regularly.

Calcium is doing four jobs at once: holding bone together, controlling how nerves fire, letting muscle contract, and — easy to forget — helping blood clot.

Three things regulate it: parathyroid hormone, vitamin D and calcitonin.

If calcium is too low, nerves and muscles become over-excitable — cramps and spasms, sometimes fits. Correct a severe case with calcium into a vein (usually calcium gluconate), then keep it up with a tablet such as calcium citrate. Add vitamin D if that is low too.

What causes low calcium: most often a shortage of parathyroid hormone, vitamin D or dietary calcium. Also chronic kidney failure, and long-term use of magnesium-based laxatives or osteoporosis drugs such as bisphosphonates and denosumab.

And on calcium's jobs — in the cardiovascular system it is not only clotting: it drives the heart muscle contracting and blood vessels contracting too.

You measure vitamin D by a blood test called 25-hydroxyvitamin D, or 25(OH)D. The liver converts vitamin D into this form, so it is a good reflection of how much someone actually has.

• Under 20 ng/mL — deficient.
• Over 20 — enough for healthy bones.
• But in practice you aim for 30 to 60.

Those last two are not the same question. Twenty-five is not deficient, and is still below where you would want it.

How much to give, according to the Endocrine Society:

• Under 1 year — 2000 IU a day.
• 1 to 18 years — 4000 IU a day.
• 19 and over — up to 10,000 IU a day.

Considerably more is needed for people with obesity, and for anyone on steroids or other drugs that block calcium absorption or flush calcium out.

There are two forms — D2 from plants and D3 made in your skin from sunlight — and they do essentially the same thing in the body.

Their proper names are ergocalciferol (D2) and cholecalciferol (D3).

Everything you are told about how to take these tablets comes down to one thing: do not let the tablet get stuck on the way down.

If it lodges in the gullet it burns the lining, and that can ulcerate. It is rare — about 1 in 10,000 people — but it is the most serious thing these drugs do.

It happens for four reasons, and each one tells you the instruction:

1. Not enough water → take it with plenty.
2. Taking it lying down → sit or stand up.
3. Lying down afterwards → stay upright.
4. An existing problem with the gullet → check before prescribing.

How it works: it shuts down the cells that dissolve bone, both by reducing how many there are and by poisoning the ones that swallow it while chewing through treated bone.

About half the dose goes straight into bone and stays there for years, sometimes decades. That is why the rare problems — jaw bone dying, unusual thigh fractures — become likelier the longer someone takes it. It is also why the protection carries on for years after stopping.

The prototype is alendronate (Fosamax) — the most widely used oral bisphosphonate. Four are approved for osteoporosis: alendronate, ibandronate, risedronate and zoledronic acid.

The everyday side effect is indigestion. The rare ones are musculoskeletal pain, inflammation in the eye, unusual thigh fractures and jaw bone dying.

There is a second half to the mechanism: as well as poisoning the osteoclasts that swallow it, alendronate reduces how many get recruited, and acts on osteoblasts, which then make something that blocks new osteoclasts forming.