Mast Cell Stabilisers

Mast cell stabilisers (sodium cromoglicate, nedocromil and ketotifen) inhibit release of mediators from mast cells and sensory nerve activation. Inhaled agents were used for prophylaxis in mild asthma, and they are largely replaced by inhaled corticosteroids. Nasal and eye forms remain useful in allergic disease.

Mechanism. Likely modulation of chloride channels and calcium entry limits degranulation, and effects on sensory C fibres reduce cough and reflex bronchoconstriction. Ketotifen also blocks histamine H1 receptors.

Pharmacokinetics. Gut absorption of sodium cromoglicate is under 1 percent, and about 8 percent of an inhaled dose reaches the lung. Half life is about 80 minutes, and the drug is excreted unchanged in urine and bile. Duration of action is short, so frequent dosing is needed.

Pharmacodynamics. Benefit appears after 2 to 4 weeks of regular use, and effect is weaker than inhaled corticosteroid.

Sodium cromoglicate. Pressurised inhaler 5 mg each actuation, 10 mg (2 puffs) four times daily, reduced to twice daily when controlled. Nebuliser 20 mg four times daily. Before exercise, 10 mg 10 to 15 minutes beforehand.

Nedocromil. 4 mg (2 puffs of 2 mg) two to four times daily. Withdrawn in several markets.

Ketotifen. Oral 1 mg twice daily in adults and children over 3 years, increased to 2 mg twice daily if needed. Causes sedation and weight gain.

Other forms. Sodium cromoglicate eye drops and nasal spray are used in allergic conjunctivitis and rhinitis.

Asthma. A low dose inhaled corticosteroid is more effective and is preferred. Use mast cell stabilisers only in mild asthma or exercise-induced symptoms when an inhaled corticosteroid is refused or not tolerated.

Exercise-induced bronchoconstriction. Sodium cromoglicate before exercise gives protection for 1 to 2 hours, weaker than a beta 2 agonist.

Allergic rhinitis and conjunctivitis. Prophylactic use during the allergen season, started before symptoms and taken regularly.

Region. Availability is limited in many markets, and an inhaled corticosteroid is preferred.

Adverse effects. Cough, throat irritation, paradoxical bronchospasm after inhalation, headache and, with nedocromil, bitter taste. Ketotifen causes drowsiness, dry mouth and weight gain.

Cautions. Pretreat with salbutamol if inhalation causes bronchospasm. Ketotifen sedation adds to alcohol and other sedatives.

Interactions. Few. Ketotifen with oral antidiabetic drugs calls for a platelet count, as some labels advise, and it adds sedation to central nervous system depressants.

Monitoring. Symptoms and reliever use after 4 weeks. Stop if there is no benefit.

Special groups. Pregnancy and breastfeeding: sodium cromoglicate has a good safety record. Children: used from age 5 in inhaled form. Older adults: sedation with ketotifen. Hepatic and renal impairment: reduce dose in severe impairment because excretion is by urine and bile.

Referral and escalation. Failure to control symptoms after 4 weeks needs a switch to an inhaled corticosteroid.