Leukotriene Antagonists, Theophylline & Other Controllers
When an inhaled steroid and a bronchodilator aren't quite enough, a handful of other controllers can be added — each working in a different way. One is a convenient tablet for mild asthma and allergies, one is a powerful but tricky old drug that needs blood tests, and one is a preventer you take before you meet your trigger. Knowing what each is for rounds out the asthma toolkit.
The mainstays of asthma control are the inhaled steroid and, added to it, a long-acting bronchodilator. But some patients need more, or need an alternative, and that's where a small group of add-on controllers comes in. They don't replace the steroid — they supplement it — and each attacks the disease from a different angle: one blocks a specific inflammatory chemical, one relaxes airway muscle by an old and unusual route, and one stops the allergy cells from firing in the first place. None is a first choice, but each has a niche worth understanding.
Leukotriene receptor antagonists
Montelukast — a convenient oral add-on, especially with allergy. Leukotrienes are inflammatory chemicals released in asthma that cause bronchoconstriction, mucus and swelling. The leukotriene receptor antagonists — montelukast is the one you'll meet — block their receptor, giving a mild anti-inflammatory and bronchodilating effect. Montelukast's appeal is that it's a once-daily tablet rather than an inhaler, which makes it useful as an add-on to an inhaled steroid, particularly in patients who also have allergic rhinitis (it helps both) or who struggle with inhalers, and it's often used in children. It's generally well tolerated, but one caution has become prominent: it can cause neuropsychiatric effects — mood changes, sleep disturbance, vivid dreams and, rarely, more serious mood symptoms — so patients (and parents) are warned to watch for these. Effective and convenient, but a supporting player, not a substitute for the steroid.
Theophylline and mast-cell stabilizers
Theophylline is an old bronchodilator (a methylxanthine, related to caffeine) that relaxes airway muscle. It works, but it's difficult and increasingly a second-line choice for one big reason: it has a narrow therapeutic index — the gap between an effective dose and a toxic one is small, so blood levels must be monitored. Too much causes nausea and vomiting, a fast or irregular heartbeat, and at high levels seizures. Worse, it's metabolised by liver CYP enzymes, so it's a magnet for drug interactions (a direct callback to the metabolism chapter): enzyme inhibitors push its level up toward toxicity, enzyme inducers drop it and lose its effect. Powerful but high-maintenance. The mast-cell stabilizers (sodium cromoglicate) work quite differently — they stop mast cells, the allergy cells, from releasing their inflammatory contents. Crucially, they only PREVENT; they can't relieve an attack already underway, so they must be taken regularly beforehand or before a known trigger (like exercise). They're very safe but weak and now little used, mostly of historical and conceptual interest. So of these three add-ons: montelukast is the convenient modern one, theophylline the powerful-but-tricky old one, and cromoglicate the safe-but-feeble preventer.
- Montelukast (leukotriene antagonist) = oral add-on, good with allergic rhinitis and in children.
- Montelukast caution: neuropsychiatric effects (mood/sleep changes) — warn patients.
- Theophylline (methylxanthine) is a bronchodilator with a NARROW therapeutic index — monitor levels.
- Theophylline is metabolised by CYP → many drug interactions (inducers/inhibitors shift its level).
- Mast-cell stabilizers (cromoglicate) PREVENT only, can't relieve an attack; safe but weak, rarely used.
Theophylline is the respiratory chapter's best example of two ideas from the pharmacokinetics section colliding in one drug. First, a narrow therapeutic index: the effective dose and the toxic dose sit uncomfortably close, so you can't just prescribe and forget — you have to measure blood levels, exactly the situation where drug monitoring earns its keep. Second, CYP metabolism: because the liver clears theophylline through CYP enzymes, anything that induces or inhibits those enzymes swings its level dramatically — an inhibitor can tip a stable patient into toxicity, an inducer can silently rob them of effect. It's a living reminder that a drug isn't just its mechanism; how the body handles it can matter just as much, and here it's the reason a once-common drug slipped to second-line.
- Using montelukast as a substitute for the inhaled steroid — it's an add-on, not a replacement.
- Not warning about montelukast's neuropsychiatric effects, especially in children.
- Prescribing theophylline without monitoring levels or checking for CYP interactions.
- Expecting a mast-cell stabilizer to relieve an acute attack — it only prevents.
Why must theophylline blood levels be monitored?
- Montelukast (leukotriene antagonist): oral add-on, good with allergic rhinitis/children; watch mood/sleep.
- Theophylline: effective bronchodilator but narrow therapeutic index + CYP interactions → monitor.
- Mast-cell stabilizers (cromoglicate): prevent only, safe but weak, rarely used now.
- All are add-ons to the inhaled steroid — none replaces it.
- Katzung BG. Basic & Clinical Pharmacology — Drugs Used in Asthma (leukotriene antagonists, methylxanthines, cromones).
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Leukotriene modifiers & methylxanthines.
- GINA — Global Initiative for Asthma (add-on controllers).
- Whalen K. Lippincott Illustrated Reviews: Pharmacology — Leukotriene antagonists & theophylline.
