Sodium Cromoglycate and Nedocromil

Nedocromil, which is structurally different from cromoglycate, also has multiple anti-inflammatory actions (Barnes, 1993c). For example, nedocromil can decrease allergen-induced plasma leakage in guinea-pig airways (Evans et al., 1988b). This effect probably involves the inhibition of mediator release (Moqbel eta.1., 1988). However, an action on vascular endothelial cells 

---

Okayama, Y., Benyon, RC., Rees, P.H., Lowman, M.A., Hillier, K. and Church, M.K. (1992). Inhibition profiles of sodium cromoglycate and nedocromil sodium on mediator release from mast cells of human skin, lung, tonsil, adenoid and intestine. Clin. Exp. Allergy 22, 401-409. 

The chromone group (e.g. sodium cromoglycate and nedocromil) are important antiallergic and antiinflammatory drugs, as well as antiasthmics and other uses, though their mode of action is imperfecfly understood. 

In children with asthma the effect of prophylactic pharmaceutical treatment has been documented in several clinical trials [131]. Inhaled steroids are very efficacious in preventing exacerbations, reducing hospitalisations and even mortality. Sodium cromoglycate and nedocromil sodium have an effect in mild-to-moderate asthma, but are less efficacious than inhaled steroids [131]. None of these treatments are curative, and after cessation of prophylactic treatment symptoms usually reappear [132-135]. 

Robuschi M, Gambaro G, Setini P, et al. Attenuation of aspirin-induced bronchoconstriction by sodium cromoglycate and nedocromil sodium. Am J Respir Crit Care Med 1997 155 1461-1464. 

Steroidal and nonsteroidal anti-inflammatory drugs such as corticosteroids, sodium cromoglycate, and nedocromil sodium, respectively, are used to treat asthma and COPD. In the sections below, we present potential targets for these... 

Both disodium cromoglycate and nedocromil sodium have antitussive effects in humans. In this instance, their activity occurs by increasing the depolarisation of sensory nerves, which increases the threshold for an action potential and therefore inhibits the activity of these neurons. 

The majority of the marketed products are used for asthma and COPD. Typical agents that are used for these indications are fl2-agonists such as salbutamol (albuterol), Terbutalin or formoterol, corticosteroids such as budesonide, FUxotide or beclomethasone and mast-cell stabilizers such as sodium cromoglycate or nedocromil. 

Cromolyn sodium (disodium cromoglycate) and nedocromil sodium are stable but extremely insoluble salts (see structures below). When used as aerosols (by nebulizer or metered-dose inhaler), they effectively inhibit both antigen- and exercise-induced asthma, and chronic use (four times daily) slightly reduces the overall level of bronchial reactivity. However, these drugs have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm they are only of value when taken prophylactically. 

In addition to the introduction of beta-agonist HFC MDIs, there is a growing number of controller medications available as HFC MDIs. These include beclomethasone, fluticasone, disodium cromoglycate, and nedocromil sodium. Further product introductions are anticipated in the coming years however, it should be noted that some products cannot or will not be reformulated with HFCs as MDIs and so alternatives (such as DPIs) are being developed. It was estimated that in 2002 there were over 100 million HFA MDIs produced globally, representing approximately 25% of worldwide MDI production. 

Cromolyn Sodium (disodium cromoglycate) and Nedocromil Sodium... 

The importance of spacers and all techniques to improve delivery is relative. If the dose delivered the old way achieves maximum pharmacodynamic effect, improving delivery is moot [53]. This observation raises other questions about aerosol drug delivery, namely, the effective dose. It is likely that the dose overkill concept has been the reason for failure to show differences when some applications were compared. A new, refined device may not be more effective than an older one because the older one delivers such a large dose that, despite inefficiency, it is pharmacodynamically equivalent. At least one study shows no difference in protection from exercise-induced asthma by nedocromil sodium and by sodium cromoglycate via MDI, and use of a spacer did not change results [54]. 

---