Antibiotic and Antiviral Agents

Under pathological conditions involving mucus hypersecretion and diminished mucociliary function (such as cystic fibrosis), bacterial organisms may colonize the airways and produce infection, a process that leads to pulmonary tissue damage. Antibiotics are administered to reverse the lung infection by killing the responsible bacteria, most commonly either Pseudomonas aeruginosa or Staphylococcus aureus. In general, short-term therapy involves intravenous administration of high doses of antibiotics and oral antibiotics for prophylactic therapy. Aerosol administration has been suggested for the delivery of antibiotics that are not orally active and as an alternative to the oral route of antibiotic administration because, in general, high blood levels of antibiotics (which increase the chance of systemic toxicity) are necessary to attain adequate concentrations in the sputum [88]. Aerosolized antibiotics have the advantage of delivering high concentrations directly to the site of infection and reducing the systemic concentrations of antibiotic. This approach is best illustrated by tobramycin, an aminoglycoside commonly used to treat pulmonary infections associated with cystic fibrosis [89]. High systemic concentrations necessary to be effective against pulmonary P. aeruginosa can cause nephrotoxicity and ototoxicity. As a result, tobramycin has been formulated for inhalation as a nebulized solution and proven to be effective in the treatment of P. aeruginosa in cystic fibrosis patients [89,90]. Pentamidine is administered as an aerosol for the treatment of and prophylaxis against Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome [91]. Like tobramycin, pulmonary delivery minimizes systemic side effects while maintaining a desirable therapeutic effect. The success of these agents portend the development of other antibiotics as inhalation treatment of lung diseases in the future [92].

Ribavirin is a virustatic agent approved for administration as an aerosol for the treatment of lower respiratory tract infections caused by respiratory syncytial virus [93,94]. However, its therapeutic efficacy in this disease has come into question of late [95]. A newer group of antiviral agents have been developed that inhibit neuraminidase, a viral enzyme necessary for the release of viruses from infected cells. Oseltamivir and zanamivir, examples of neuraminidase inhibitors, can be used to treat influenza A and B [96]. Zanamivir, having low oral bioavailability [97], is administered intranasally or by inhalation as a dry powder, whereas oseltamivir is taken orally [98].

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Diabetes 2

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