Indications
Benzonatate is primarily indicated for the symptomatic relief of cough. It is utilized in managing coughs associated with both acute and chronic respiratory conditions, providing an effective option for patients experiencing persistent coughing.
Pharmacodynamics
The pharmacodynamic profile of benzonatate involves the suppression of cough by desensitizing pulmonary stretch receptors that are integral to the cough reflex mechanism. Although there are limited clinical trials available, earlier studies have shown that benzonatate can inhibit both experimentally induced and subjectively measured pathological cough without affecting the respiratory center when used at recommended dosages. The medication begins to take effect within 15 to 20 minutes of administration, and its action lasts approximately 3 to 8 hours.
Absorption
Upon oral administration, benzonatate is absorbed into the systemic circulation through the gastrointestinal tract. In clinical studies with healthy Chinese volunteers, a 100 mg dose of benzonatate yielded a maximum concentration (Cmax) of 1063 ± 460 ng/mL, demonstrating its absorption efficiency.
Metabolism
Benzonatate undergoes metabolic transformation primarily through hydrolysis by plasma butyrylcholinesterase (BChE). This process converts benzonatate to its major metabolite, 4-(butylamino)benzoic acid (BABA), which plays a role in the drug's pharmacological activity.
Mechanism of Action
Benzonatate functions as a local anesthetic, exerting its effects primarily through the peripheral anesthetization of vagal stretch receptors or nerve fibers found in the respiratory passages, lungs, and pleura. This anesthetic action leads to a reduction in the activity of these receptors. Typically, when stretch receptors are stimulated, they transmit impulses to the cough center in the medulla via an afferent pathway composed of sensory nerve fibers or the vagus nerve. These impulses then generate an efferent response that activates the expiratory muscles to produce a cough. By anesthetizing these receptors, benzonatate effectively inhibits the cough reflex and the subsequent cough production. Additionally, benzonatate impedes the transmission of cough reflex impulses within the vagal nuclei of the medulla. Among its various proposed mechanisms, benzonatate is also recognized for its ability to potently inhibit voltage-gated sodium channels.
