Pharmacological modulation of cough reflex

The cough reflex is an attack of powerful expiratory efforts produced by active contractions of the expiratory muscles, preceded by deep inspirations. Cough is a normal physiological defensive reflex responsible for keeping the airways free of obstruction and harmful substances. However, cough is also the most frequent symptom of acute respiratory system diseases and is the most common reason why sick patients visit physicians. The largest diagnostic group associated with chronic cough is asthma or asthma-like syndromes and chronic obstructive pulmonary disease. Furthermore, gastroesophageal reflux, rhinitis/postnasal drip syndrome and unpleasant side effects accompanying the therapy with angiotensin-converting enzyme inhibitors (ACEI) represent other causes of chronic cough. The cough reflex may be elicited by the activation of receptors of non-myelinated nociceptive Aδ-fibers and C-fibers and receptors of myelinated Aδ-fibers distributed throughout the respiratory tract. In recent times as proper cough receptors are thought to be rapidly adapting receptors (RARs) of myelinated fibers, C-fibers and transient receptor potential vanilloid 1 (TRPV1) localize on the non-myelinated fibers. As the pathological cough (especially its chronic form) has significant impact on patient's quality of life, observed either in physical activity or psychosocial domain, various treatment attitudes are used for different forms of cough (acute, subacute, chronic, productive, nonproductive, psychogenic, asthma-associated, or painful). Interest of research in this field is accompanied with the fact, that many antitussive drugs (mainly from the opioid group), which have been the antitussives of choice for decades, are limited by their unpleasant and very often adverse reactions. In this chapter the authors divided the drugs used in the pharmacological treatment of cough into several groups. These include the drugs acting at the level of receptors, the drugs affecting the propagation of cough impulses in afferent nerves, the drugs modulating the central coordination of cough reflex, the drugs acting at the level of efferent nerves, and the drugs affecting the effectors. Efficacy of many antitussive agents is connected with their influence on more than one level of cough reflex. Another group used in the therapy of cough are mucoactive substances that change the dry, irritant and nonproductive cough into the so-called productive cough with nonirritating expectoration. The last-mentioned group in this chapter is demulcerative and hydrating drugs, which can create a defense layer protecting the mucous membranes from other irritant stimuli.