Asthmatic

The use of metered-dose valves in aerosol medical appHcations permits an exact dosage of an active dmg to be deHvered to the respiratory system where it can act locally or be systemicaHy absorbed. For example, inhalers prescribed for asthmatics produce a fine mist that can penetrate into the bronchial tubes (see Antiasthmatic agents). 

Oxygen inhalators are used as a first-aid measure for a long Hst of emergencies, including heart attacks and suffocation, and as a result are carried routinely by rescue squads. Oxygen—helium mixtures have proved beneficial in asthmatic attacks, because these permit more rapid flow of gas into congested areas of the respiratory system. 

In 1981, Chinese Restaurant Asthma was reported following capsule administration of MSG to several asthmatics (37). However, the researchers failed to account for other allergens to which the subjects could have been exposed and did not utilize the scientific practice of a "control" substance which would have helped to determine if glutamate triggered this response. In a double-blind crossover study, chronic asthmatics were challenged with MSG or a placebo. No decrease in pulmonary function was observed (39). 

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

Intrinsic asthma, also called idiopathic asthma, usually develops in adulthood. In intrinsic asthma allergic factors are not demonstrable. Episodes of intrinsic asthma may be triggered by a variety of stimuli, eg, emotional state, exposure to cold air, or inert dusts. Both intrinsic and extrinsic asthmatics can be prone to exercise-induced attacks. Individuals who experience a combination of extrinsic and intrinsic asthmatic reactions have mixed asthma. Status asthmaticus refers to an especially acute life-threatening asthma attack which is resistant to normal treatments and which may require hospitalization in order to stabilize the patient. 

Elevation of cycHc AMP levels is also known to inhibit the release of inflammatory and contractile mediators from mast cells (42). The good clinical efficacy of P2" goiAsts may be related to this action because some members of this class of dmgs inhibit mediator release at the same concentrations at which they relax smooth muscle (43). In contrast to their effectiveness against immediate bronchoconstriction, P2" gonists do not inhibit the late asthmatic... 

Single dose or short-term treatment with aerosolized steroids inhibits both the late asthmatic response and allergen-induced bronchial hyperresponsiveness (45,92). However it does not affect the early asthmatic response nor does it induce bronchodilation (45,92). Long-term treatment with steroids protects against both the early and late asthmatic responses and also reduces bronchial hyperresponsiveness (44,71,86,93). Over time, the airways relax (dilate) and measures of airway function, such as forced expiratory volume in one second (FEV ), gradually return to almost normal levels. 

The first SRS-A antagonist, FPL-55712 (26) (149), was discovered before the stmctures of the leukotrienes were detemiined. Although this compound is relatively weak as an antagonist and suffers from a very short half-life in vivo, it played an important role both in leukotriene stmcture elucidation and as a model for later antagonists. In work stmcturaHy related to FPL-55712, LY-171883 was developed (27) (150). LY-171883 was evaluated in several clinical trials before development was stopped. Orally adrninistered, LY-171883 blocked slightly the response to aerosol LTD improved pulmonary function (FEV ) in mild asthmatics (151), decreased the sensitivity of asthmatics to cold air-induced bronchoconstriction (152), and significantly reduced the bronchoconstrictor response to inhaled antigen (153). However, in all these studies the beneficial effects were minimal. 

Cromakalim. Cromakalim has along half-life (254). Cromakalim at an oral dose of 1.5 mg ia humans significantly lowers blood pressure 19/12 mm Hg (systohc/diastoHc pressure). It iacreases reaal blood flow, PRA, and heart rate. Cromakalim has bronchodilating activity that is beneficial for hypertensive asthmatic patients. Because of some undesirable effects seen ia cardiac papillary muscles of animals oa long-term treatmeat, future clinical trials are to be carried out usiag the active enantiomer, lemakalim (BRL 38227). 

Caution should be taken when using glutaraldehyde. Gloves and aprons should be worn and adequate ventilation provided. It has been reported to produce contact dermatitis, eye irritation, nausea, headache, rashes, and asthmatic reaction (125). 

If a known adverse health effect can reasonably be anticipated under the circumstances of work - and could readily be observed - some form of heahh surveillance is appropriate. This may involve a doctor or trained nurse. It may include the checking of employees skin for dermatitis or asking questions relevant to any asthmatic condition where work is with recognized causative agents (e.g. epoxy resin curing agents). 

A general description of the three major classes of MDI s and brief descriptions of adhesive applications are shown in Table 1. More recently, MDl has become the isocyanate of choice in adhesives, partly because MDI has a lower vapor pressure than TDI does (see pp. 296-297 in [18]). Isocyanates have been shown to cause an allergic reaction in a small percentage of the population. This reaction can manifest itself in the form of an asthmatic condition [19]. Before starting work with isocyanates, researchers are encouraged to read about the proper precautions to take, in order to work safely with these materials. Researchers should also check with their local health and environmental safety representatives [20]. 

Exposure to sulfur dioxide in the ambient air has been associated with reduced lung function, increased incidence of respiratory symptoms and diseases, irritation of the eyes, nose, and throat, and premature mortality. Children, the elderly, and those already suffering from respiratory ailments, such as asthmatics, are especially at risk. Health impacts appear to be linked especially to brief exposures to ambient concentrations above 1,000 ixg/in (acute exposures measured over 10 minutes). Some epidemiologic studies, however, have shown an association between relatively low annual mean levels and excess mortality. It is not clear whether long-... 

Nasal vasculature may offer some insight into this question, though research to date has been equivocal. Nasal turbinate vessels can be classified as either capacitance vessels or resistive vessels. Capacitance vessels appear to vasodilate in response to infection while resistance vessels appear to respond to cold stimuli by vasoconstriction. Buccal vascular structures also respond to thermal stimuli but appear to respond principally to cutaneous stimuli. How pharyngeal and tracheobronchial submucosal vessels react to thermal stimuli is not known, though cold-induced asthma is believed to result from broncho-spasms caused by susceptible bronchial smooth muscle responding to exposure to cold dry air.- This asthmatic response suggests an inadequate vascular response to surface cooling. 

FIGURE 5.19 Relationship of transpleural pressure to volume >n normal and asthmatic individuals. 

Forced expiration is commonly used to assess pulmonary function in both healthy and impaired individuals. Static measures of lung volumes (TLC, Vj, FRC) fail to detect dynamic changes in pulmonary function that are attributable to disease (e.g., asthmatic airway constriction). Obtaining maximum expiratory flow-volume (MEFV) curves (Fig. 5.21) permits derivation of key parameters in detecting changes in lung function. 

The 2-aminooxazole analogue, isamoxole (74), is an anti asthmatic agent. Its synthesis follows the classic pattern of condensation of hydroxy acetone with ji-propylcyanamide to establish the heterocyclic ring (21) The synthesis of isamoxole (74)... 

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