Benzonatate acts peripherally by anesthetizing the stretch receptors of vagal afferent fibers located in the alveoli of the lungs, the bronchi, and the pleura. The drug may also act centrally by inhibiting the transmission of the cough reflex at the level of the medulla where the vagal afferent impulse is transmitted to the motor nerves. In patients with asthma, intravenously administered benzonatate increased minute ventilation, rate and depth of respiration. However, overall lung volume and expiratory flow rate were not altered. At recommended oral dosages, benzonatate has no inhibitory effect on the respiratory center; however, in overdosage, the pharmacology of benzonatate resembles that of other ester-type local anesthetics. Clinical effects include initial CNS stimulation, which is followed by CNS depression and respiratory compromise.
When applied locally, as in the oropharynx prior to intubation or endoscopy, benzonatate acts like other local anesthetics. The drug blocks the generation and conduction of nerve impulses at the level of the cell membrane. Local anesthetics bind directly within the intracellular portion of voltage-gated sodium channels. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying benzonatate around the nerve trunks or ganglia supplying the area to be anesthetized. Benzonatate provides anesthesia in roughly 1—2 minutes after direct topical application to the oropharynx, noticeable clinically as the loss of the gag reflex.
"During the past year we have had occasion to see 24 patients with normal menstrual cycles, but who, following the use of synthetic progestational agents (The Pill), had one or more of the following conditions as their chief complaint: irregular menses, amenorrhea, and infertility." Communication with other clinics indicates that there are hundreds of such cases that are unreported. "Let's Be Honest About The Pill" and inform nulliparous women, and those with only one living child of the possibility of being relatively infertile for undeterminate periods of time following discontinuation of oral contraceptives." - JAMA 195:780-782, Feb. 28,1966.