ATC Group: R03D Other systemic drugs for obstructive airway diseases

Aminophylline is a soluble derivative of theophylline and is given for its theophylline activity. Aminophylline relaxes smooth muscle and relieves bronchial spasm. It stimulates the myocardium and reduces venous pressure in congestive heart failure, leading to a marked increase in cardiac output.

Bamifylline is a methylxanthinic derivative with two side chains in position 7 and 8, distinguishing it clearly from theophylline. Bamifylline carries out a bronchospasmolytic action on the smooth musculature and also blocks the action of the bronchoconstriction mediators. Unlike theophylline, bamifylline usually has no exciting effects on the central nervous system.

Benralizumab is an anti-eosinophil, humanised afucosylated, monoclonal antibody (IgG1, kappa). It specifically binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα). The IL-5 receptor is specifically expressed on the surface of eosinophils and basophils. The absence of fucose in the Fc domain of benralizumab results in high affinity for FcɣRIII receptors on immune effector cells such as natural killer (NK) cells. This leads to apoptosis of eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), which reduces eosinophilic inflammation.

Bufylline is a combination of theophylline and aminoisobutanol used as a bronchodilator. It also acts and may be used as a diuretic.

Choline theophyllinate is the choline salt of theophylline. It has a strong bronchodilator action, due to the relaxation of the smooth muscle fibers of the bronchi.

Diprophylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree. The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of the bronchial smooth muscle. Diprophylline exerts its bronchodilatory effects directly and, unlike theophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Because of this, dyphylline pharmacokinetics and plasma levels are not influenced by various factors that affect liver function and hepatic enzyme activity, such as smoking, age, congestive heart failure, or concomitant use of drugs which affect liver function.

Fenspiride has an anti-inflammatory and bronchodilator activity. These properties are most likely due to several concomitant mechanisms of action. It is used as symptomatic treatment in the course of inflammatory diseases of the bronchi and lungs.

Mepolizumab is a humanised monoclonal antibody (IgG1, kappa), which targets human interleukin-5 (IL-5) with high affinity and specificity. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation and survival of eosinophils. Mepolizumab is indicated as an add-on treatment for severe refractory eosinophilic asthma.

Montelukast is an orally active compound which binds with high affinity and selectivity to the CysLT1 receptor. Τhe CysLT type-1 (CysLT₁) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis.

Omalizumab is a recombinant DNA-derived humanised monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab binds to IgE and prevents binding of IgE to FcεRI (high-affinity IgE receptor) on basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the allergic cascade. Treatment of atopic subjects with omalizumab resulted in a marked down-regulation of FcεRI receptors on basophils.

Reslizumab is a humanised monoclonal antibody (IgG4, κ) against the human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5 and interferes with IL-5 binding to its cell-surface receptor. IL-5 is a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. Reslizumab binds human IL-5 with picomolar affinity blocking its biological function; consequently survival and activity of eosinophils are reduced.

Roflumilast is a PDE4 inhibitor, a non-steroid, anti-inflammatory active substance designed to target both the systemic and pulmonary inflammation associated with COPD.

Tezepelumab is a monoclonal antibody (IgG2λ) directed against thymic stromal lymphopoietin (TSLP), preventing its interaction with the heterodimeric TSLP receptor. In asthma, both allergic and non-allergic triggers induce TSLP production. Blocking TSLP with tezepelumab reduces a broad spectrum of biomarkers and cytokines associated with airway inflammation; however, the mechanism of action of tezepelumab in asthma has not been definitively established.

Theophylline is a bronchodilator. In addition it affects the function of a number of cells involved in the inflammatory processes associated with asthma and chronic obstructive airways disease. Theophylline stimulates the myocardium and produces a diminution of venous pressure in congestive heart failure leading to marked increase in cardiac output.

Zafirlukast is a selective and competitive receptor antagonist of leukotriene D₄ and E₄ (LTD₄ and LTE₄), components of slowreacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.