Page 1022 - Basic _ Clinical Pharmacology ( PDFDrive )

1008 SECTION IX Toxicology

Nitrogen Oxides used. These measures include maintenance of gas exchange with
adequate oxygenation and alveolar ventilation. Drug therapy
Nitrogen dioxide (NO ) is a brownish irritant gas sometimes associ- may include bronchodilators, sedatives, and antibiotics. New
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ated with fires. It is formed also from fresh silage; exposure of farm- -induced ARDS have been
ers to NO in the confines of a silo can lead to silo-filler’s disease, a approaches to the management of NO 2
developed and considerable controversy now exists about the pre-
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severe and potentially lethal form of acute respiratory distress syn- cise respiratory protocol to use in any given patient.
drome. The disorder is uncommon today. Miners who are regularly
exposed to diesel equipment exhaust have been particularly affected
by nitrogen oxide emissions with serious respiratory effects. Today, Ozone & Other Oxides
the most common source of human exposure to oxides of nitrogen,
including NO , is automobile and truck traffic emissions. Recent Ozone (O ) is a bluish irritant gas found in the earth’s atmo-
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air pollution inventories in cities with high traffic congestion have sphere, where it is an important absorbent of ultraviolet light
demonstrated the important role that internal combustion engines at high altitude. At ground level, ozone is an important pollut-
have in the increasing NO urban air pollution. A variety of dis- ant. Atmospheric ozone pollution is derived from photolysis of
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orders of the respiratory system, cardiovascular system, and other oxides of nitrogen, volatile organic compounds, and CO. These
problems have been linked to NO exposure. compounds are produced primarily when fossil fuels such as
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gasoline, oil, or coal are burned or when some chemicals (eg, sol-
1. Mechanism of action—NO is a relatively insoluble deep lung vents) evaporate. Nitrogen oxides are emitted from power plants,
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irritant. It is capable of producing pulmonary edema and acute motor vehicles, and other sources of high-heat combustion.
adult respiratory distress syndrome (ARDS). Inhalation damages Volatile organic compounds are emitted from motor vehicles,
the lung infrastructure that produces the surfactant necessary to chemical plants, refineries, factories, gas stations, paint, and other
allow smooth and low-effort lung alveolar expansion. The type I sources. More information on ground-level ozone and its sources
cells of the alveoli appear to be the cells chiefly affected by acute and consequences may be found at https://www.epa.gov/arc-x/
low to moderate inhalation exposure. At higher exposure, both climate-adaptation-ground-level-ozone-and-health.
type I and type II alveolar cells are damaged. If only type I cells Ozone can be generated in the workplace by high-voltage elec-
are damaged, after an acute period of severe distress, it is likely that trical equipment, and around ozone-producing devices used for
treatment with modern ventilation equipment and medications air and water purification. Agricultural sources of ozone are also
will result in recovery. Some patients develop nonallergic asthma, important. There is a near-linear gradient between exposure to
or “twitchy airway” disease, after such a respiratory insult. If severe ozone (1-hour level, 20–100 ppb) and bronchial smooth muscle
damage to the type I and type II alveolar cells occurs, replacement of response. See Table 56–1 for the current PEL for ozone.
the type I cells may be impaired; progressive fibrosis may ensue that
eventually leads to bronchial ablation and alveolar collapse. This 1. Mechanism of action and clinical effects—Ozone is an
can result in permanent restrictive respiratory disease. In addition to irritant of mucous membranes. Mild exposure produces upper
the direct deep lung effect, long-term exposure to lower concentra- respiratory tract irritation. Severe exposure can cause deep lung
tions of nitrogen dioxide has been linked to cardiovascular disease, irritation, with pulmonary edema when inhaled at sufficient
increased incidence of stroke, and other chronic disease. concentrations. Ozone penetration in the lung depends on tidal
The current PEL for NO is given in Table 56–1. Exposure volume; consequently, exercise can increase the amount of ozone
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to 25 ppm of NO is irritating to some individuals; 50 ppm is reaching the distal lung. Some of the effects of O resemble
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moderately irritating to the eyes and nose. Exposure for 1 hour those seen with radiation, suggesting that O toxicity may result
to 50 ppm can cause pulmonary edema and perhaps subacute or from the formation of reactive free radicals. The gas causes shal-
chronic pulmonary lesions; 100 ppm can cause pulmonary edema low, rapid breathing and a decrease in pulmonary compliance.
and death. Enhanced sensitivity of the lung to bronchoconstrictors is also
observed. Exposure around 0.1 ppm O 3 for 10–30 minutes causes
2. Clinical effects—The signs and symptoms of acute exposure irritation and dryness of the throat; above 0.1 ppm, one finds
to NO include irritation of the eyes and nose, cough, mucoid or changes in visual acuity, substernal pain, and dyspnea. Pulmonary
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frothy sputum production, dyspnea, and chest pain. Pulmonary function is impaired at concentrations exceeding 0.8 ppm.
edema may appear within 1–2 hours. In some individuals, the Airway hyperresponsiveness and airway inflammation have
clinical signs may subside in about 2 weeks; the patient may then been observed in humans. The response of the lung to O 3 is a
pass into a second stage of abruptly increasing severity, including dynamic one. The morphologic and biochemical changes are the
recurring pulmonary edema and fibrotic destruction of terminal result of both direct injury and secondary responses to the initial
bronchioles (bronchiolitis obliterans). Chronic exposure of labora- damage. Long-term exposure in animals results in morphologic
tory animals to 10–25 ppm NO has resulted in emphysematous and functional pulmonary changes. Chronic bronchitis, bronchi-
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changes; thus, chronic effects in humans are of concern. olitis, fibrosis, and emphysematous changes have been reported in
a variety of species, including humans, exposed to concentrations
3. Treatment—There is no specific treatment for acute intoxi- above 1 ppm. Increased visits to hospital emergency depart-
cation by NO ; therapeutic measures for the management of ments for cardiopulmonary disease during ozone alerts have been
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deep lung irritation and noncardiogenic pulmonary edema are reported. A study of the basic physiologic responses of humans to