22.10 — Respiratory Drugs

Studies of inhaler technique repeatedly find that the majority of people using a pressurised inhaler make at least one error big enough to reduce the dose reaching the lungs, and a substantial proportion get almost none of it in.

Which means the commonest cause of an inhaler "not working" is not the drug and not the disease.

A correctly used cheap inhaler beats an incorrectly used expensive one every time.

The two colours, and what they actually do

Blue — the reliever. Opens the airways within minutes. Does nothing to the underlying inflammation.

Brown, orange, purple, red — the preventer. Reduces inflammation over days and weeks. Does nothing you can feel.

And the mismatch between those two sentences is the central problem in asthma (Chapter 21.1): the one that feels useful is not the one keeping you alive.

Bronchodilators

Short-acting beta-2 agonists

Salbutamol (albuterol in the US), terbutaline.

They are agonists at beta-2 receptors on airway smooth muscle (Chapter 22.1), which relaxes the muscle and widens the airway.

Onset within 5 minutes, lasting 4 to 6 hours.

Side effects follow directly from beta-2 receptors elsewhere: tremor of the hands, palpitations, and a fall in potassium at high doses — which is why potassium is checked after repeated nebulisers in a severe attack.

And the reliever inhaler is a monitoring tool as much as a treatment. Needing it more than twice a week, or getting through more than about three inhalers a year, means the underlying inflammation is not controlled. That is a prompt to review treatment, not to order more inhalers.

Using a reliever alone, without an inhaled steroid, is no longer recommended in asthma and is associated with worse outcomes.

Long-acting beta-2 agonists

Salmeterol, formoterol, vilanterol. Lasting 12 to 24 hours.

Formoterol is worth singling out because it is both fast and long-acting — onset within minutes like salbutamol, duration of 12 hours. Which is what makes the combined preventer-and-reliever approach possible: every rescue puff delivers an anti-inflammatory at the same time.

And a firm rule: in asthma, a long-acting beta agonist is never used without an inhaled steroid. Given alone, they were associated with increased asthma deaths — the airway opens while the inflammation continues unchecked. Every asthma product containing one now also contains a steroid, which is a regulatory response to that finding.

Antimuscarinics

Ipratropium (short-acting), tiotropium, glycopyrronium, umeclidinium (long-acting).

They block acetylcholine at airway muscarinic receptors, removing the constricting signal from the parasympathetic nerves (Chapter 11.9).

Particularly useful in COPD, where this pathway contributes more than in asthma.

Side effects: dry mouth, and caution in glaucoma if the mist reaches the eyes, which is a reason to use a mouthpiece rather than a loose mask where possible. Urinary retention in men with prostate enlargement.

Ipratropium is added to salbutamol in severe attacks, where the combination works better than either alone.

Theophylline

An older oral bronchodilator, related to caffeine.

Narrow therapeutic index, requires blood level monitoring, and interacts with a long list of drugs — and it is a good illustration of Chapter 22.1, because the same drug is useful at one level and causes vomiting, arrhythmias and seizures a little above it.

Largely superseded, and still used where the alternatives are unavailable or insufficient.

Inhaled corticosteroids

Beclometasone, budesonide, fluticasone, ciclesonide, mometasone.

They reduce airway inflammation by changing gene expression in airway cells (Chapter 22.1) — which is why they take days to weeks to reach full effect and why they cannot rescue an attack.

What they do: reduce symptoms, reduce attacks, reduce hospital admissions, and reduce asthma deaths. This is the drug that changes the course of the disease.

The dose is a tiny fraction of an oral steroid dose, delivered locally, which is why the systemic effects are so much smaller.

Local side effects and how to avoid them:

Oral thrush and hoarseness, from drug deposited in the mouth and throat.

Prevented by rinsing the mouth and spitting after each use, and by using a spacer, which catches the large particles that would otherwise hit the back of the throat.

Systemic effects at high doses over long periods: some effect on bone density, a small effect on growth in children, and adrenal suppression at very high doses.

And on children specifically, the honest position: inhaled steroids cause a small reduction in growth velocity, with studies suggesting a final adult height difference of around 1 centimetre. Uncontrolled asthma affects growth more than that, and it kills people. The trade is clear, and it is worth stating plainly because fear of steroids is a major cause of under-treatment.

Combination inhalers

Steroid plus long-acting beta agonist — the standard for asthma not controlled on a steroid alone.

Triple therapy — steroid plus long-acting beta agonist plus long-acting antimuscarinic, in one device. Used in severe asthma and in COPD with frequent exacerbations.

And in COPD, inhaled steroids are used more selectively, mainly where there are frequent exacerbations or a raised blood eosinophil count, because they increase pneumonia risk in that population (Chapter 21.1).

The devices, and how to use them

Pressurised metered-dose inhaler:

Shake. Breathe out fully. Seal your lips around the mouthpiece. Start a slow deep breath in and press the canister at the same time. Keep breathing in slowly for 4 to 5 seconds. Hold your breath for 10 seconds. Wait 30 seconds before a second puff.

The errors that matter most: not breathing out first, pressing before or after the breath rather than with it, breathing in too fast, and not holding the breath.

With a spacer, all of that gets easier: press once into the chamber, then take 5 slow breaths in and out through it, or one slow deep breath and hold. Use it within seconds of pressing, and one puff at a time — two puffs fired into a chamber together stick to each other and to the walls.

Wash the spacer in warm soapy water and let it drip dry rather than rinsing and wiping, because rubbing it dry builds a static charge that attracts the drug to the plastic.

Dry powder inhalers: breathe out away from the device, then take a fast, deep, forceful breath in, and hold for 10 seconds.

The opposite technique to the aerosol inhaler, and the commonest reason someone switched between devices stops getting benefit.

And a specific point: a dry powder inhaler needs enough inspiratory force to work. Someone very breathless, very frail or very young may not generate it, which is a reason to choose an aerosol with a spacer instead.

Nebulisers — for severe attacks and people who cannot manage a device. No better than an inhaler with a spacer for most acute asthma.

Checking your technique with a pharmacist or nurse once a year is one of the highest-value five minutes in medicine.

Oral and injected treatments

Oral corticosteroids — prednisolone, for acute attacks.

A short course of 5 to 7 days does not need tapering, though longer courses do, because the adrenal glands become suppressed (Chapter 22.12).

Started early in an attack, because they take hours to work — which is precisely why waiting to see whether things improve wastes the time they need.

Leukotriene receptor antagonists — montelukast.

Blocking leukotrienes, inflammatory molecules particularly involved in exercise-induced and aspirin-sensitive asthma.

Taken as a tablet, which suits people who struggle with inhalers.

And it carries a specific warning worth knowing: neuropsychiatric effects — vivid dreams, nightmares, anxiety, agitation, low mood, and rarely suicidal thoughts, including in children. Regulators have issued formal warnings. Anyone starting it should be told to report mood or behaviour changes.

Biologics for severe asthma — omalizumab against IgE; mepolizumab, reslizumab and benralizumab against the IL-5 pathway; dupilumab against IL-4 and IL-13; tezepelumab acting further upstream.

They target the specific immune pathway driving that person's asthma, which is why blood eosinophil counts and IgE levels are measured to decide which one.

And the effect in the right patient is substantial — people who spent years on repeated steroid courses becoming nearly attack-free (Chapter 21.1).

Roflumilast — for severe COPD with chronic bronchitis and frequent exacerbations.

Azithromycin — used long-term at low dose in some people with frequent exacerbations, for its anti-inflammatory effect as much as its antibacterial one. Balanced against resistance and hearing effects.

Cough and cold remedies

And the honest assessment is short.

Cough suppressants — dextromethorphan, pholcodine, codeine. The evidence that they work better than a placebo syrup is weak. Honey has evidence at least as good for cough in children over one year, and it is safer.

Honey is never given under 12 months, because of infant botulism risk.

Expectorants and mucolytics — guaifenesin, carbocisteine. Modest evidence. Carbocisteine has reasonable evidence in COPD for reducing exacerbations.

Decongestants — pseudoephedrine orally, xylometazoline as a spray.

Sprays must not be used beyond about five days, because of rebound congestion that becomes self-sustaining and is genuinely hard to escape.

Oral decongestants raise blood pressure and heart rate, so they are avoided in hypertension, heart disease and with certain antidepressants.

And cough and cold medicines are not given to children under 6, because of harm without demonstrated benefit — a change made after serious adverse events. Fluids, honey over 12 months, saline drops and paracetamol are the answer.

What matters most

Preventer daily, even when you feel well — that is what stops the attack.

Reliever counts as a warning light, not a treatment plan.

Technique checked, spacer used, mouth rinsed.

A written action plan, which reduces admissions because it converts judgement into instructions.

Annual flu vaccination, and pneumococcal where indicated.

And stopping smoking, which is the only thing that changes the trajectory of COPD.

What the next page fixes

Chapter 22.11 covers the drugs that act on the brain — antidepressants, antipsychotics, sedatives and stimulants, and the practical rules for taking and stopping them.