Lesson focus: Mast-cell stabilisers are preventive anti-allergic medicines. They reduce the release of chemical mediators from sensitised mast cells, helping to prevent symptoms before they start. They are not bronchodilators, do not reverse an established acute asthma attack, and must never replace emergency treatment for anaphylaxis.
Core idea: Use these medicines regularly or before a predictable trigger. They work best as prevention, not rescue.
Learning objectives
By the end of this lesson, the student should be able to explain mast-cell activation in allergy; classify the mast-cell stabilisers; describe the mechanisms, routes, uses, adverse effects and limitations of individual agents; distinguish prophylaxis from reliever treatment; and counsel a patient safely on inhaled, nasal and ophthalmic preparations.
1. Where mast-cell stabilisers fit in allergic disease
Allergic disease begins when a sensitised person encounters an allergen again. Examples include house-dust mite, pollen, animal dander, mould, occupational sensitizers, exercise in a susceptible patient, cold air, smoke and other airway irritants. In asthma, the consequences include bronchial smooth-muscle contraction, mucosal oedema and increased mucus secretion. Together, these narrow the airways and cause wheeze, breathlessness, cough and chest tightness.
Mast-cell stabilisers are traditionally grouped among the preventive anti-asthmatic drugs. The supplied anti-asthmatic-drugs lecture correctly places them beside bronchodilators, leukotriene antagonists, glucocorticoids and anti-IgE therapy, but their action is distinct:
| Drug group | Main action | Role in an acute attack |
|---|---|---|
| Short-acting beta2-agonist (for example salbutamol) | Rapid bronchodilation | Reliever treatment; use according to the acute-asthma plan |
| Inhaled corticosteroid | Broad anti-inflammatory controller effect | Not an immediate bronchodilator; key long-term controller therapy |
| Leukotriene receptor antagonist | Blocks cysteinyl-leukotriene effects | Preventive add-on in selected patients |
| Mast-cell stabiliser | Reduces mediator release from mast cells | No: not a rescue bronchodilator |
| Adrenaline | Alpha- and beta-adrenergic effects | Essential first-line treatment for anaphylaxis; not routine chronic-asthma controller therapy |
Do not confuse prevention with treatment of deterioration. A patient with severe breathlessness, inability to speak full sentences, cyanosis, exhaustion, altered consciousness, silent chest or poor response to a reliever needs urgent assessment and acute-asthma treatment. Do not delay this while giving cromoglicate or another mast-cell stabiliser.
2. Mast cells and the allergic response
Mast cells are immune cells found in tissues that interface with the environment, including the skin, nasal mucosa, conjunctiva, gastrointestinal tract and respiratory mucosa. Their granules contain preformed mediators, especially histamine. They also generate newly synthesised mediators after activation.
Sensitisation and re-exposure: the examination sequence
- First exposure: an allergen stimulates a type-2 immune response and production of allergen-specific IgE.
- Sensitisation: IgE binds high-affinity Fc epsilon RI receptors on mast cells and basophils.
- Re-exposure: the allergen cross-links adjacent IgE molecules on the mast-cell surface.
- Activation: intracellular signalling and calcium-dependent processes lead to degranulation and mediator synthesis.
- Clinical effects: airway smooth-muscle contraction, increased vascular permeability and oedema, mucus secretion, itching, redness and recruitment of other inflammatory cells.
Important mediators include histamine, cysteinyl leukotrienes (LTC4, LTD4 and LTE4), prostaglandins, platelet-activating factor, proteases and cytokines. Histamine contributes to itching, vasodilatation and increased vascular permeability. Leukotrienes are potent, sustained bronchoconstrictors and increase mucus production and mucosal oedema. This explains why an allergic symptom can be more than “histamine alone”.
3. Mechanism of mast-cell stabilisers
Mast-cell stabilisers reduce the tendency of activated mast cells to release inflammatory mediators. Sodium cromoglicate (also called cromolyn sodium) is the prototype. Its full molecular mechanism is not represented by one simple receptor interaction, but clinically it is understood as reducing calcium-dependent mast-cell degranulation and mediator release. Effects on other inflammatory cells and airway sensory pathways may also contribute.
The result is less release of histamine, leukotrienes, prostaglandins and other mediators after allergen or irritant exposure. Therefore these medicines can reduce bronchial hyper-responsiveness and prevent some symptoms induced by triggers. They do not directly relax contracted bronchial smooth muscle. Once major bronchospasm is established, their onset is too slow and their action is unsuitable for rescue.
Memory line: Stabilise before the storm; do not expect it to open an already closed airway.
4. Drugs in this group
Sodium cromoglicate / cromolyn sodium
Prototype mast-cell stabiliser. Used locally by inhaled, nasal or ophthalmic routes; oral preparations may be used for selected gastrointestinal symptoms associated with mast-cell disease. Very little is absorbed systemically from most local preparations.
Nedocromil sodium
Pharmacologically similar preventive agent. It has had an inhaled role in asthma but availability varies greatly and it is now uncommon or discontinued in many settings.
Ketotifen
An orally active drug with both H1-antihistamine and mast-cell-stabilising properties. It is slow in onset and may cause sedation; do not describe it as an acute reliever.
Ophthalmic mast-cell stabilisers
Examples used in some settings include sodium cromoglicate, lodoxamide and pemirolast. Several modern eye preparations combine antihistamine activity with mast-cell stabilisation; local formulary availability differs.
5. Sodium cromoglicate in detail
Pharmacokinetics and route
Sodium cromoglicate is poorly absorbed from the gastrointestinal tract. This is why oral administration is not useful for ordinary asthma prevention, whereas inhaled delivery places the drug at the airway surface. Nasal sprays and eye drops deliver local treatment to the nose and conjunctiva. Low systemic absorption explains the generally favourable systemic safety profile, but it does not mean that the medicine is risk-free or that inhaler technique is unimportant.
Asthma and trigger-induced bronchospasm
In asthma, cromoglicate is a prophylactic medicine. It may be considered for prevention of symptoms in selected patients, including symptoms provoked predictably by allergens, exercise, cold air or inhaled irritants. It must be taken as prescribed and may be used before a known trigger when the product and clinical plan recommend this. It should not be used alone to manage an asthma exacerbation.
Response is not immediate. Patients must be told that controller benefit may require regular use for days to weeks, and persistent symptoms require review of diagnosis, inhaler technique, exposure to triggers and the current anti-inflammatory regimen. In modern asthma care, inhaled corticosteroid-containing treatment is generally more effective for controlling airway inflammation, so cromoglicate has a limited, often historical role in many formularies.
Allergic rhinitis
Intranasal cromoglicate may reduce sneezing, rhinorrhoea and nasal itching when used regularly. It is a local preventive choice for selected patients, but it is often less convenient and less effective than an intranasal corticosteroid for persistent moderate or severe rhinitis. A non-sedating oral or intranasal antihistamine may also be appropriate depending on the symptom pattern. The patient should not expect a nasal mast-cell stabiliser to relieve severe obstruction immediately.
Allergic conjunctivitis
Ophthalmic sodium cromoglicate is useful for prevention or control of allergic conjunctival symptoms such as itching, tearing and redness, particularly where symptoms recur during an allergy season or after an unavoidable exposure. Teach the patient to wash hands, avoid touching the dropper tip, instil the prescribed number of drops, close the eye gently and apply nasolacrimal occlusion when advised. Contact lenses should be managed according to the individual product instructions.
Other uses
The supplied lecture notes allergic dermatitis among potential topical prophylactic uses. In practice, use depends on the formulation and diagnosis; eczema and other inflammatory skin disease often need different management. Oral cromolyn/cromoglicate is also used in some jurisdictions for gastrointestinal symptoms related to mast-cell disorders such as mastocytosis. This specialised use should be prescribed and monitored by the relevant clinician.
6. Nedocromil sodium
Nedocromil has broadly similar preventive pharmacology: it reduces mediator release and does not act as a direct bronchodilator. Historical teaching describes it as an inhaled prophylactic option for asthma, including in older children and adults. Availability and licensing have changed over time, so students should always check the local formulary rather than assuming it can be prescribed. If a patient already uses it, the same safety principles apply: regular preventive use, correct device technique, a separate reliever plan, and review if cough, wheeze or breathlessness worsens after inhalation.
7. Ketotifen
Ketotifen deserves a separate description because it is not simply inhaled cromoglicate in another form. It is orally active, has H1-receptor blocking activity as well as mast-cell-stabilising effects, and has a slow onset of benefit. Sedation, impaired concentration and weight/appetite effects may occur. Counsel patients to avoid driving, alcohol or other sedatives until they know how it affects them. It is not a treatment for acute asthma, acute urticaria with airway compromise or anaphylaxis.
8. Choosing the correct formulation
| Clinical problem | Possible local formulation | Key counselling point |
|---|---|---|
| Predictable mild asthma symptoms or exercise/allergen trigger in a selected patient | Inhaled or nebulised cromoglicate where available | Preventive only; keep and know how to use the prescribed reliever |
| Seasonal or recurrent allergic rhinitis | Nasal cromoglicate | Use regularly; compare response with evidence-based first-line nasal therapy |
| Allergic conjunctivitis | Cromoglicate or other mast-cell-stabilising eye drops | Correct drop technique and avoid contaminating the bottle tip |
| Selected mast-cell gastrointestinal disorder | Oral cromolyn/cromoglicate in places where licensed | Specialist-directed use; not routine oral asthma treatment |
9. Adverse effects, precautions and interactions
Because local preparations have little systemic absorption, serious systemic toxicity is uncommon. The adverse effects are usually local and route-specific, but every patient who reports worsening breathing after a dose must be assessed carefully.
- Inhaled preparations: throat irritation, cough, unpleasant taste, nausea, mild wheeze and, rarely, paradoxical bronchospasm.
- Nasal preparations: local irritation, sneezing, nasal discomfort or epistaxis.
- Eye drops: transient stinging, burning, blurred vision immediately after instillation or local irritation.
- Hypersensitivity: rash, swelling or respiratory symptoms are uncommon but require stopping the suspected product and urgent assessment when severe.
- Ketotifen: drowsiness, dizziness, dry mouth, increased appetite or weight gain may be clinically important.
Paradoxical bronchospasm: If wheeze, chest tightness or breathlessness occurs immediately after inhalation, stop the dose, use the patient’s prescribed quick-relief medicine if indicated, and seek urgent review. Repeatedly forcing further doses may be dangerous.
Clinically important drug interactions are less prominent with topical cromoglicate than with many systemic medicines, but interaction checking should still include the exact product, route and excipients. In pregnancy, breastfeeding, children, older adults, renal impairment or liver disease, avoid blanket statements: choose the preparation based on current product information, local guideline and individual risk-benefit assessment. Low systemic absorption is reassuring but is not a substitute for prescribing review.
10. Device technique: a preventable cause of treatment failure
For an inhaled product, correct technique determines whether medicine reaches the lungs. Check the actual device at every review. A common exam answer is not merely “teach inhaler use,” but “ask the patient to demonstrate; correct errors; use a spacer with a pressurised metered-dose inhaler when appropriate; then re-check technique.”
General metered-dose inhaler steps
- Remove cap and inspect the mouthpiece.
- Shake the inhaler if the product instructions require it.
- Exhale gently away from the device.
- Seal lips around the mouthpiece or spacer.
- Begin a slow deep breath and actuate one puff; continue to inhale slowly and deeply.
- Hold the breath for about 5–10 seconds if able, then exhale gently.
- Wait between puffs if another puff is prescribed, and clean/store the device as directed.
Dry-powder devices require a quick, deep inhalation and are not used in the same way as a pressurised inhaler. Nebulisers may be used in selected circumstances, but a nebuliser is not automatically superior and should not falsely reassure a patient during severe asthma; clinical severity and response must be assessed.
11. Practical asthma safety: what mast-cell stabilisers do not replace
The supplied lecture includes a useful acute severe asthma framework: oxygen, repeated inhaled short-acting beta2-agonist, inhaled anticholinergic therapy in appropriate severe attacks, systemic corticosteroid and correction of clinically relevant dehydration/electrolyte problems under urgent clinical care. The exact protocol and doses are facility-specific and should follow current local guidance. Mast-cell stabilisers have no role as first aid for this emergency.
Students should also remember drug triggers. Aspirin and other NSAIDs can precipitate bronchospasm in susceptible people, and non-selective beta-blockers may worsen asthma. This does not mean every patient with asthma must never receive these drugs; it means the history, risk and alternatives need deliberate assessment. Cholinergic drugs may also worsen bronchoconstriction.
12. Comparison with related anti-allergic medicines
| Medicine | Most useful for | Important distinction |
|---|---|---|
| Mast-cell stabiliser | Preventing mediator release before/repeatedly during exposure | Preventive; no direct bronchodilation |
| H1-antihistamine | Histamine-mediated itch, sneezing and urticaria symptoms | Acts at histamine receptors after histamine release; does not treat all asthma inflammation |
| Inhaled corticosteroid | Long-term airway anti-inflammatory control | Usually more central to contemporary asthma controller therapy |
| Leukotriene receptor antagonist | Selected asthma/allergic-rhinitis phenotypes | Blocks leukotriene action, rather than stabilising mast cells |
| Anti-IgE biologic | Selected severe allergic asthma | Reduces free-IgE signalling upstream; specialist treatment |
13. Patient counselling checklist
- Explain the exact target: asthma prevention, nasal allergy or allergic eye disease.
- State clearly that the medicine is not a reliever for sudden breathlessness.
- Confirm the patient has an up-to-date asthma action plan if they have asthma.
- Demonstrate the device or drops, then ask for a return demonstration.
- Emphasise regular use and realistic expectations about onset.
- Review technique, adherence, trigger exposure and symptom control rather than simply increasing doses.
- Tell the patient to seek urgent care for severe or worsening breathlessness, facial/tongue swelling, collapse, cyanosis or poor response to their prescribed reliever.
14. Clinical reasoning cases
Case 1: “My cromoglicate did nothing during the attack.”
A student with known asthma uses an old cromoglicate inhaler after developing severe wheeze during a football match. Explain that this is expected: cromoglicate is not a rescue bronchodilator. Assess severity, use the prescribed reliever/action plan and arrange urgent escalation if there are danger signs. Later, review trigger prevention and controller treatment.
Case 2: Seasonal itchy red eyes
A patient develops bilateral itching and tearing every pollen season, without pain, marked photophobia or visual loss. An ophthalmic mast-cell stabiliser may be useful when used regularly. However, unilateral severe pain, reduced vision, corneal opacity, purulent discharge, trauma or contact-lens-associated red eye requires prompt clinical eye assessment rather than routine allergy treatment.
Case 3: Persistent nasal symptoms
A patient uses nasal cromoglicate only when congestion becomes severe and reports little benefit. The likely problem is both timing and treatment selection. Confirm adherence and technique; explain regular preventive use; then consider whether persistent moderate/severe rhinitis requires first-line intranasal corticosteroid therapy or another guideline-based regimen.
15. High-yield viva and written-answer points
- Name three mast-cell stabilisers: sodium cromoglicate/cromolyn sodium, nedocromil sodium and ketotifen.
- State their mechanism: they reduce mast-cell degranulation and release of mediators such as histamine, leukotrienes and prostaglandins.
- Are they bronchodilators? No.
- Can sodium cromoglicate abort an acute asthma attack? No.
- Why is cromoglicate usually administered locally? It is poorly absorbed orally and works at the site of allergic inflammation.
- Give uses: selected asthma prophylaxis; prevention of trigger-induced bronchospasm; allergic rhinitis; allergic conjunctivitis; and selected specialist mast-cell gastrointestinal indications.
- Name an important inhaled adverse effect: cough, throat irritation or paradoxical bronchospasm.
- What must be checked before labelling a drug ineffective? Diagnosis, adherence, trigger exposure, device technique and correct drug role.
16. Summary
Mast-cell stabilisers are classic anti-allergic preventive drugs. Their value is in preventing mediator release from sensitised mast cells, especially before predictable exposure or during recurrent local allergic disease. Sodium cromoglicate is the key prototype; nedocromil has a similar but increasingly limited/availability-dependent role; and ketotifen combines mast-cell-stabilising and H1-antihistamine properties. The safety message is decisive: they are not rescue bronchodilators and never replace urgent treatment for severe asthma or anaphylaxis.
