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Adrenergic beta blockers --- Heart --- Heart Diseases --- Congresses --- Diseases --- Chemotherapy --- Congresses

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Adrenergic beta blockers --- Neuropsychopharmacology --- Propranolol --- Pharmacology --- Congresses. --- Textbooks & monographs 1891-2000 --- Textbooks & monographs 1891-2000.

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Adrenergic beta blockers --- Cardiovascular system --- Adrenergic beta-Antagonists --- Cardiovascular Diseases --- Diseases --- Chemotherapy --- therapeutic use --- drug therapy

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Hypertension is a growing medical concern in the United States. With an increasing number of Americans suffering from hypertension every year, the use of antihypertensive medications such as beta-blockers has increased as well. Three beta-blocker medications--atenolol, metoprolol, and propranolol--were among the 200 most prescribed drugs in the United States in 2003, ranked 4, 14, and 165, respectively. Pilots that successfully manage their hypertension either with diet, exercise, and/or medication may remain medically certified to operate an aircraft. However, these pilots are closely monitored to ensure that their hypertension is properly controlled. The FAA classifies approximately 8% of all active civil aviation pilots as "hypertensive with medication." Toxicological evaluation of postmortem samples obtained from pilots is an important part of the investigation of fatal civil aviation accidents. During this evaluation it is not uncommon to detect beta-blocker compounds such as atenolol, metoprolol, or propranolol in the submitted biological samples. In forensic toxicology laboratories, these compounds are most commonly confirmed and/or quantitated by gas chromatography with mass spectrometric detection (GC/MS). Liquid chromatography coupled with mass spectrometric detection (LC/MS), however, is becoming increasingly more prevalent in the field of forensic toxicology and is considered a superior alternative to GC/MS for the analysis of many compounds. There are very few analytical LC/MS methods published for the determination of beta-blockers from biological specimens. Furthermore, we were unable to find any citation for the toxicological determination of beta-blockers in postmortem fluid and tissue specimens using LC/MS; in particular, atmospheric pressure chemical ionization (APCI) in conjunction with ion trap MS. This manuscript describes the validation and application of such a method.

Adrenergic beta blockers --- Aircraft accidents. --- Hypertension --- Propanolamines --- Adrenergic beta-Antagonists --- Accidents, Aviation. --- Aerospace Medicine --- Chromatography, Liquid --- Mass Spectrometry --- Analysis. --- Treatment. --- analysis. --- methods. --- drug therapy. --- United States.

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Pilots who are considered hypertensive are closely monitored by the Federal Aviation Administration (FAA) to ensure that their hypertension is properly controlled. During the investigation of fatal civil aviation accidents, postmortem samples obtained from pilots are submitted to the FAA's Civil Aerospace Medical Institute (CAMI) for toxicological evaluation. During such evaluation, submitted samples are analyzed for prescription and nonprescription drugs, and it is common to find beta-blocker antihypertensives such as atenolol, metoprolol, and propranolol in the submitted biological samples. During a 10-year period of 1993-2002, postmortem samples from 3290 civil aviation accident pilot fatalities (cases) were received by CAMI. Toxicological evaluation of these cases revealed that 50 of the 3290 fatalities had the commonly prescribed beta-blockers, atenolol, metoprolol, and propranolol. Out of the 50 fatalities, atenolol, metoprolol, and propranolol were found to be present in 24, 19, and 7 fatalities, respectively, but the initial analysis indicated the presence of atenolol and metoprolol in 4 of these pilot fatalities. Since (i) the combined use of both drugs was not consistent with the history of the drug use by those pilots, (ii) it is uncommon to simultaneously prescribe 2 beta-blockers, and (iii) these commonly used antihypertensives have considerable amount of chemical and structural similarity (6), further examination was undertaken for those fatality cases wherein atenolol and metoprolol were initially detected. Such examination entailed selectively and simultaneously analyzing the 3 commonly used beta-blockers in the submitted biological samples and rectifying any possible analytical interference with the antihypertensives.

Air pilots --- Aircraft accidents --- Forensic toxicology --- Adrenergic beta blockers --- Adrenergic beta-Antagonists --- Atenolol --- Gas Chromatography-Mass Spectrometry. --- Metoprolol --- Propranolol --- Sensitivity and Specificity. --- Mortality --- Drug use --- Analysis. --- isolation & purification.