Beta-blockers analysis

Boutitie F, Boissel JP, ConnoUy SJ, Camm AJ, Cairns JA, Juhan DG, Gent M, Janse MJ, Dorian P, Frangin G. Amiodarone interaction with beta-blockers analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators. Circulation 1999 99(17) 2268-75. 

T. Hyotylainen, T. Andersson and M. E. Riekkola, Eiquid cliromatographic sample cleanup coupled on-line with gas chromatography in the analysis of beta-blockers in human serum and urine , 7. Chromatogr. Sci. 35 280-286 (1997). 

Figure 15.4 Separation of mixtures of beta-blockers by using micellar HPLC, employing the following mobile phases (a) 0.12M SDS, 5% propanol, 0.5% tiiethylamine (b) 0.06 M SDS, 15% propanol (c) 0.1 IM SDS, 8% propanol. Adapted from Journal of Chromatographic Science, 37, S. Carda-Broch et al., Analysis of urine samples containing cardiovascular drugs by micellor liquid chromatography with fluorimetric detection , pp. 93-102, 1999, with permission from Preston Publications, a division of Preston Industries, Inc.

Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure a Bayesian meta-analysis. Ann Intern Med 2001 134(7) 550-60. 

Bangalore S et al Beta-blockers for primary prevention of heart failure in patients with hypertension Insights from a meta-analysis. J Am Coll Cardiol 2008 52 1062. [PMID 18848139]... 

Shekelle PG et al Efficacy of angiotensin-converting enzyme inhibitors and beta blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status A meta-analysis of major clinical trials. J Am Coll Cardiol 2003 41 1529. [PMID 12742294]... 

Sanbe H, Haginaka J (2003) Restricted access media-molecularly imprinted polymer for propranolol and its application to direct injection analysis of beta-blockers in biological fluids. Analyst 128(6) 593-597... 

Kintz, P. and Mangin, P., Hair analysis for detection of beta-blockers in hypertensive patients, Eur. J. Clin. Pharmacol, 42, 351, 1992. 

The utility of hair in the detection of chronic beta-blocker administration was examined by Kintz and Mangin in 8 hypertensive patients. Betaxolol (3 cases, 1.2-2.7 ng/mg), sotalol (2 cases, 4.4-5.3 ng/mg), atenolol (1 case, 0.9 ng/mg), and propanolol (2 cases, 1.6-2.4 ng/mg) were identified. Relative changes in observance of treatment was revealed by sectional hair analysis in a case of betaxolol treatment. 

MacLeod, S.L. Sudhir, P Wong, C.S., Stereoisomer analysis of wastewater-derived beta-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography-tandem mass spectrometry J. Chromatogr. A 2007, 1170, 23-33. 

In a systematic review, the beneficial interaction has been confirmed (249). Four groups of patients who had been studied in EMIAT and CAMIAT (SEDA-21, 198) were defined patients who had taken amiodarone plus beta-blockers, patients who had taken beta-blockers or amiodarone alone, and patients who had taken neither. The relative risks for all-cause mortality and all forms of cardiac death or resuscitated cardiac arrest were lower in the patients who had taken amiodarone plus beta-block-ers than in the other three groups. The results of this post hoc analysis should be regarded with caution, but in view of previous similar reports they are suggestive of a beneficial interaction of amiodarone with beta-blockers in patients who have had a previous myocardial infarction. The interaction was statistically significant for cardiac deaths and for dysrhythmic deaths or resuscitated cardiac arrest. In all other cases the relative risk was reduced, although not significantly. The risk was not affected by heart rate. This interaction has been reviewed (250). 

Intermittent claudication has also been reported to be worsened by beta-adrenoceptor antagonists, but has been difficult to document because of the difficulty of study design in patients with advanced atherosclerosis. As early as 1975 it was reported from one small placebo-controlled study that propranolol did not exacerbate symptoms in patients with intermittent claudication (70). This has subsequently been supported by the results of several large placebo-controlled trials of beta-blockers in mild hypertension and reports of trials of the secondary prevention of myocardial infarction, in which intermittent claudication was not mentioned as an adverse effect, even though it was not a specific contraindication to inclusion (71). In addition, a comprehensive study of the effects of beta-adrenoceptor antagonists in patients with intermittent claudication did not show beta-blockade to be an independent risk factor for the disease (72). In men with chronic stable intermittent claudication, atenolol (50 mg bd) had no effect on walking distance or foot temperature (73). These findings have been confirmed in a recent meta-analysis of 11 randomized, controlled trials to determine whether beta-blockers exacerbate intermittent claudication (SEDA-17, 234). 

Retroperitoneal fibrosis has been reported in patients taking oxprenolol (224), atenolol (225), propranolol (226), metoprolol (227), sotalol (228), and timolol (including eye-drops) (229,230). However, this disorder often occurs spontaneously and has been reported very infrequently in patients taking beta-blockers (231). Thus, in the absence of any causal relation it is most likely that it reflects the spontaneous incidence in patients taking a common therapy. This conclusion has been supported by an analysis of 100 cases of retroperitoneal fibrosis (232). 

Sax MJ. Analysis of possible drug interactions between cimetidine (and ranitidine) and beta-blockers. Adv Ther 1988 5 210. 

The best overall evidence of the safety of diuretics in old people comes from the large-scale outcome trials in hypertensive patients (11,13,15,17,18). These studies in over 10000 subjects aged over 60 years showed clearly that thiazide-based treatment reduces the risk of stroke, coronary heart disease events, and cardiovascular events in older hypertensive patients. A meta-analysis (163) of randomized trials lasting at least 1 year and involving 16164 individuals aged at least 60 years showed that diuretics were superior to beta-blockers with regard to all endpoints (stroke, coronary heart disease events, cardiovascular mortality, and all-cause mortality). The beneficial effects noted in these trials should dispel any doubts about the safety and efficacy of diuretics in old people. 

NSAIDs inhibited the effects of aU antihypertensive drug categories. However, in patients taking beta-block-ers and vasodilators, NSAIDs produced a greater increase in supine mean blood pressure than in patients taking diuretics, but only the pooled inhibitory effect of NSAIDs on the effects of beta-blockers achieved statistical significance. When the data were analysed by tjrpe of NS AID the meta-analysis showed that aU NSAIDs increased supine blood pressure, and that piroxicam, indometacin, and ibuprofen produced the most marked increases. However, only piroxicam had a statistically significant effect with respect to placebo. Aspirin,... 

Meissner G, Hartonen K, Riekkola LL. Supercritical-fluid extraction combined with solid-phase extraction as sample preparation technique for the analysis of beta-blockers in resum and urine. Fresenius J Anal Chem 1998 360 618-621. 

Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta-blockers in patients with reactive airway disease A meta-analysis. Ann Intern Med 2002 137 715-725. 

Rosenthal J, Bahrmann H, Benkert K, et al. Analysis of adverse effects among patients with essential hypertension receiving an ACE inhibitor or a beta-blocker. Cardiology 1996 87 409-414. 

Houghton T, Freemantle N, Cleland JG, et al. Are beta-blockers effective in patients who develop heart failure soon after myocardial infarction A meta-regression analysis of randomised trials. Eur J Heart Fail 2000 2 333-340. 

The use of reaction sequences is also common in the analysis of pharmaceuticals. For example, for the purity test for hydrochlorothiazide (HCT) the DAB specifies a nitration reaction followed by reaction with naphthylethylenediamine dihydrochloride, in which the reaction sequence is performed as in the example given below. HCT is a diuretic which is often used in combination with beta-blockers for the treatment of hypertension (high blood pressure). Diuretics of this type are also abused in sport (doping) and appear on the list of banned substances prepared by the IOC (International Olympic Committee). In the quantitative determination of HCT in urine, the red azo dyes formed in the derivatization (parent substance and metabohtes) is regarded as a doping-positive result [111]. The complete specification for this analytical method, known as Application A-43.2, can be obtained from CAM AG. 

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