The Respiratory Tract

Principles of fluid and particle dynamics in the respiratory tract (physical and anatomical parameters) are also discussed, as they are the starting point for the development of drug products for inhalation. In fact, they set the conditions used for in vitro and in vivo testing of inhalation systems and define the specifications for new inhalation systems. 

5 Pulmonary Drug Delivery Delivery To and Through the Lung 

Total lung capacity Inspiratory capacity Functional residual capacity 

Vital capacity Inspiratory reserve volume Tidal volume 

The volume of air in the lung after a maximal inspiratory effort The volume of air maximally inspired after a normal tidal expiration 

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Repeated exposures of animals to high (near-lethal) concentrations of vapors result in inflammation of the respiratory tract, as weU as degenerative changes in the Hver, kidneys, and heart muscle. These effects arise at concentrations far above those causing irritation. Such effects have not been reported in humans. The low odor threshold and irritating properties of acrylates cause humans to leave a contaminated area rather than tolerate the irritation. 

Chlorine gas is a respiratory irritant and is readily detectable at concentrations of <1 ppm in air because of its penetrating odor. Chlorine gas, after several hours of exposure, causes mild irritation of the eyes and of the mucous membrane of the respiratory tract. At high concentrations and in extreme situations, increased difficulty in breathing can result in death through suffocation. The physiological response to various levels of chlorine gas is given in Table 19. 

Toxicity. Fluorine is extremely corrosive and irritating to the skin. Inhalation at even low concentrations irritates the respiratory tract at high concentrations fluorine inhalation may result in severe lung congestion. 

Hydrogen chloride in air is an irritant, severely affecting the eye and the respiratory tract. The inflammation of the upper respiratory tract can cause edema and spasm of the larynx. The vapor in the air, normally absorbed by the upper respiratory mucous membranes, is lethal at concentrations of over 0.1% in air, when exposed for a few minutes. HCl is detectable by odor at 1—5 ppm level and becomes objectionable at 5—10 ppm. The maximum concentration that can be tolerated for an hour is about 0.01% which, even at these levels, causes severe throat irritation. The maximum allowable concentration under normal working conditions has been set at 5 ppm. 

Magnesium vanadates, as vanadium compounds in general, are known irritants of the respiratory tract and conjunctiva. The threshold limit value (TLV) for vanadium compounds in air recommended by the National Institute of Occupational Safety and Health is 0.05 mg/m based on a typical 8-h workday and 40-h workweek (7,147). Chronic inhalation can lead to lung diseases such as bronchitis, bronchopneumonia, and lobar pneumonia. These dust-related effects can be avoided by use of individual respirators in areas where exposure is likely. 

The relative toxicities of thallium compounds depend on their solubHities and valence states. Soluble univalent thallium compounds, eg, thaHous sulfate, acetate, and carbonate, are especiaHy toxic. They are rapidly and completely absorbed from the gastrointestinal tract, skin peritoneal cavity, and sites of subcutaneous and intramuscular injection. Tb allium is also rapidly absorbed from the mucous membranes of the respiratory tract, mouth, and lungs foHowing inhalation of soluble thallium salts. Insoluble compounds, eg, thaHous sulfide and iodide, are poorly absorbed by any route and are less toxic. 

The likelihood that materials will produce local effects in the respiratory tract depends on their physical and chemical properties, solubiHty, reactivity with fluid-lining layers of the respiratory tract, reactivity with local tissue components, and (in the case of particulates) the site of deposition. Depending on the nature of the material, and the conditions of the exposure, the types of local response produced include acute inflammation and damage, chronic... 

At processing temperatures, most polymers emit fumes and vapors that may be irritating to the respiratory tract. This is also tme for PVC and its additives. Such irritation may extend to the skin and eyes of sensitive people. Processing emissions exposure can also be greatly reduced or eliminated by the use of properly designed and maintained exhaust ventilation. 

Health and Safety Factors. Neopentanoic acid possesses low toxicity, either by ingestion (oral LD q in rats is 2.0 g/kg) or by skin absorption (dermal LD q in rabbits is 3.16 g/kg). The principal ha2ards associated with neopentanoic acid at ambient temperatures are from eye and skin irritation. At elevated temperatures, where concentrations of the vapor are significant, irritation of the respiratory tract can also occur. Contact with the material should be avoided. 

Some of the criteria used in the selection of a suitable agent are effectiveness in extremely small concentrations time to onset of action effectiveness through various routes of entry into the body, such as the respiratory tract, eyes, and skin stability in long-term storage and ease of dissernination in feasible munitions. 

Repeated or prolonged contact with the skin, especially under clothing, may result in local irritation and inflammation, and at elevated temperatures such as in the presence of an open flame, chloroform decomposes to form by-products, including phosgene, chlorine, and hydrogen chloride, all of which are severe irritants to the respiratory tract. 

Side effects associated with narcotics include nausea, anorexia, and constipation most of them also diminish ciUary activity and produce a drying effect on the respiratory tract mucosa. 

For sensitive individuals, reduction in pulmonary lung function chest discomfort irritation of the respiratory tract, coughing and wheezing. Threshold for injury to vegetation... 

TOTAL INHALABLE DUST Airbome material capable of entering the nose and mouth during breathing and hence available for deposition in the respiratory tract. 

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