Introduction
an important caveat that is usually assumed but rarely emphasized. Antitussive drugs are classified as peripheral or central based on their site(s) of action Cough is the most common reason why sick patients visit physicians in the United States. 1 Antitussive drugs following systemic administration. Many techniques used to determine the site of action of antitussive such as codeine and dextromethorphan are among the most commonly used prescription and over-the drugs involve non-systemic routes of administration. These methods are best combined with other tech-counter drugs in the world. 2 These drugs suppress the responsiveness of one or more components of the niques involving systemic administration to provide convincing evidence regarding the site of action of an reflex pathway for cough and are intended to be useful against cough of diverse aetiologies. [3][4] While most of antitussive drug. the currently available antitussive drugs are relatively old, there are several new compounds currently under development or being marketed by pharmaceutical PERIPHERAL ANTITUSSIVE DRUGS companies. 5,6 Ironically, relatively little is known about how most antitussive drugs act to inhibit cough. It is A variety of methods have been used to investigate possible peripheral actions of antitussive drugs. Most therefore important to consider the mechanism of action of this large class of drugs. The purpose of of these methods are based on the idea that the drug in question inhibits the response of one or more this report is to review the mechanisms of action of antitussive drugs and the methods by which this types of airway sensory afferent to mechanical and/ or chemical stimuli that produce cough. These information has been generated. Other informative reviews exist on the subject. [7][8][9][10][11] methods fall into several broad categories: direct recording of sensory afferent responses, evaluation of the activity and/or relative potency of the drug after administration by different routes (inhalation, intra-CLASSIFICATION OF ANTITUSSIVE DRUGS venous, intra-arterial, and/or intracerebroventricular), and blockade of the activity of the putative peripheral Antitussive drugs are broadly classified into two groups based on their site of action: peripheral or drugs by quaternary antagonists that penetrate the CNS only to a limited extent. Each method has central. Peripheral antitussive drugs act outside the central nervous system (CNS) to inhibit cough, pre-specific advantages and limitations and, as such, a combination of two or more methods usually is the sumably by suppressing the responsiveness of one or more vagal sensory receptors that produce cough. 7,11 strongest approach. Central antitussive drugs act inside the central nervous system to suppress the responsiveness of one or more Sensory afferent responses components of the central reflex pathway for cough. 12,13 These definitions are also largely based on the concept
The inhibitory effect of an antitussive drug on the responsiveness of one or more types of sensory affer-that peripheral drugs penetrate the CNS to a limited extent and central drugs penetrate the CNS relatively ents responsible for cough provides evidence consistent with, but not sufficient for, concluding that the easily to reach their site of action. While this concept may be true for most drugs that have been classified compound has solely a peripheral action. A systemically administered compound may have both peri-as central or peripheral, it does not imply that central drugs have no peripheral component to their activity pheral and central sites of action. Furthermore, there are many different types of sensory afferents that can or that drugs classified as peripheral cannot act centrally to inhibit cough. This point also brings to light contribute to the production of cough and no studies