Chronic obstructive pulmonary disease drug development

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all early pulmonary drug-delivery devices, it delivered small-molecule compoimds (bronchodilators or inhaled corticosteroids) to the airways (not necessarily the deep limg) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems used for asthma and COPD the energy somces in these devices were mechanical and patient inspiration. 

The pharmacists of Care-Rite Pharmacy also developed patient educational tools to be used during the patient assessment and patient education components of the Pharmacy Check-up Service. Because many of the targeted patients have similar medical conditions, education materials were developed for specific disease states, including hypertension, ischemic heart disease, diabetes, asthma, chronic obstructive pulmonary disease (COPD), etc. Also, educational materials were developed for certain therapeutic classes of medications. The Care-Rite pharmacists also determined that many patients needed individualized education materials, so they implemented a drug information/educational service as part of the MTM service. With this service, patients can ask questions regarding their medical conditions and/or drug therapies. The pharmacists will research and provide an individualized written response for each patient. 

A 69-year-old man developed acute benzodiazepine withdrawal delirium following a short course of flunitrazepam after an acute exacerbation of chronic obstructive pulmonary disease. He was not an alcohol-or drug-abuser and he had not previously taken benzodiazepines. Six days after withdrawal of flunitrazepam he became agitated and confused, and had visual hallucinations, disorganized thinking, insomnia, increased psychomotor activity, disorientation in time and place, and memory impairment. Tachycardia and significant anxiety were also noted. He fulfilled the DSM IV criteria for withdrawal syndrome and delirium, and had spontaneous remission of symptoms within 48 hours. 

The first MDI products were developed by Riker Laboratories and marketed in 1956, using a newly patented design of metering valve. In most countries the MDI is now established as the principal dosage form of inhalation drug therapy for bronchial asthma and chronic obstructive pulmonary disease (COPD). Since its introduction, MDI technology has evolved steadily. However, with the phase-out in the commercial use of chlorofluorocarbon (CFC) propellants, which have been the mainstay of pharmaceutical MDIs, the pace of MDI technology development has accelerated with the transition to hydrofluorocarbon (HFC) propellants. ... 

Abuse of legally obtainable substances is also of growing concern worldwide. Alcohol and tobacco abuse continue to create a major burden on the economies and health care systems of most developed countries because of high rates of morbidity and mortality caused by associated diseases, including cancer, chronic obstructive pulmonary disease (COPD), hepatic cirrhosis, and others. In addition, there is substantial anecdotal evidence that abuse of prescription psychoactive drugs continues to increase as use of these synthetic pharmaceuticals becomes more widespread in many countries where they are commonly available in over-the-counter forms in the absence of professional medical advise or supervision. 

A study in 17 patients with chronic obstructive pulmonary disease found that nizatidine 150 mg twice daily for a month had no effect on the steady-state pharmacokinetics of theophylline. However, there were 6 reports of apparent interactions in the Spontaneous Adverse Drug Reaction Database of the FDA in the US up to the end of August 1989. Four patients taking theophylline developed elevated serum theophylline levels, with symptoms of toxicity in at least one case, when given nizatidine. The problems resolved when either both drugs, or just nizatidine were stopped. ... 

Terzano et al developed Polysorbate 20 niosomes containing beclomethasone dipropionate for pulmonary delivery to patients with chronic obstructive pulmonary disease. Singh et prepared niosomes containing the anti-inflammatory drug nimesulide and tested its physico-chemical properties including stability and in vitro release. It was shown that in vitro sustained drug release can be achieved with this approach. The research literature for niosomes in ocular drug delivery has been reviewed by Kaur et al." ... 

S. Onoue, et al. New treatments for chronic obstructive pulmonary disease and viable for-mulation/device options for inhalation therapy. Expert Opin DrugDeliv 6,793-811,2009. B.M. Ibrahim, et al. Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease. Expert Opin DrugDeliv 8, 451-466, 2011. 

More broadly, timolol therapy should be considered with caution in patients with any significant sign, symptom, or history for which systemic beta-blockade would be medically imwise.This includes disorders of cardiovascular or respiratory origin (e g., asthma, chronic bronchitis, and emphysema) as well as many other conditions. Spirometric evaluation after institution of timolol therapy may help to identify patients in whom bronchospasm develops after commencement of therapy. In general, however, patients with asthma and other obstructive pulmonary diseases should avoid this drug. Sympathetic stimulation may be essential to support the circulation in individuals with diminished myocardial contractility, and its inhibition by P-adrenoceptor antagonists may precipitate more severe cardiac feilure. 

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