Bifunctional Drugs for the Treatment of Respiratory Diseases

Over the last decade, there has been a steady increase in the use of fixed dose combinations for the treatment of a range of diseases, including cancer, AIDS, tuberculosis and other infectious diseases. It is now evident that patients with asthma or chronic obstructive pulmonary disease (COPD) can also benefit from the use of fixed dose combinations, including combinations of a long-acting β₂-agonist (LABA) and an inhaled corticosteroid (ICS), and combinations of LABAs and long-acting muscarinic receptor antagonists (LAMAs). There are now also "triple inhaler" fixed dose combinations (containing a LABA, LAMA and ICS) under development and already being made available in clinical practice, with the first such triple combination having been approved in India. The use of combinations containing drugs with complementary pharmacological actions in the treatment of patients with asthma or COPD has led to the discovery and development of drugs having two different primary pharmacological actions in the same molecule that we have called "bifunctional drugs". In this review we have discussed the state of the art of bifunctional drugs that can be categorized as bifunctional bronchodilators, bifunctional bronchodilator/anti-inflammatory drugs, bifunctional anti-inflammatory drugs and bifunctional mucolytic and anti-inflammatory drugs.