Search PubMed⌕ Search

Biomedical subjects

L M Lopez

Publications and source records attributed to L M Lopez.

At least 37 records · Page 2Linked to original sources

Bisoprolol: is this just another beta-blocker for hypertension or angina?

OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical experience with bisoprolol and make recommendations regarding its potential clinical usefulness, as well as considerations for formulary inclusion. DATA SOURCES: Reference citations were sought from Index Medicus and Science Citation Index. Data were collected from abstracts and articles describing experimental studies or blind clinical trials. STUDY SELECTION: Studies designed in a randomized, blind, and placebo-controlled manner were emphasized. Studies also were included if bisoprolol was evaluated comparatively with other agents in a randomized, blind fashion. DATA EXTRACTION: Data from human studies published in English were evaluated. Studies were assessed by sample size and the clarity of descriptions of methods and results. DATA SYNTHESIS: Bisoprolol reduces systolic and diastolic blood pressures in patients with hypertension for a 24-hour dosing interval and is associated with beneficial hemodynamic effects in patients with myocardial ischemia. It is devoid of intrinsic sympathomimetic activity and membrane-stabilizing effects at therapeutic dosages. In patients with hypertension, bisoprolol diminishes plasma renin activity, platelet aggregation, effective renal plasma flow, and creatinine clearance. Bisoprolol has minimal effects on glucose tolerance and plasma lipid profiles. Monotherapy with bisoprolol is as effective as with atenolol, nitrendipine, or nifedipine. Low-dose combination therapy with hydrochlorothiazide is at least as effective as either bisoprolol or hydrochlorothiazide alone. Preliminary experience in the management of angina pectoris suggests that bisoprolol is at least as efficacious as atenolol or verapamil. Thus far, reported adverse effects are similar to those of other beta-blockers. No clinically important drug interactions have been reported at this time.

Angina Pectoris↗

Alterations in nitric oxide synthase activity, superoxide anion generation, and platelet aggregation in systemic hypertension, and effects of celiprolol.

A decrease in endothelium-derived relaxing factor or nitric oxide has been proposed as a potential mechanism of increased vascular resistance in hypertension. An increase in the generation of superoxide anions, which degrade nitric oxide and induce platelet aggregation, may also compromise regional blood flow in hypertension. Recent studies show that human neutrophils generate nitric oxide, which has a similar biologic profile to the endothelium-derived relaxing factor. This study measured nitric oxide synthase activity and superoxide generation in human neutrophils and platelet aggregation in patients with essential hypertension. Nitric oxide synthase activity, measured as conversion of 3H-L-arginine to 3H-L-citrulline, in peripheral blood neutrophils was decreased in hypertensive subjects (percent conversion of 3H-L-arginine: 4.2 +/- 0.5 vs 9.0 +/- 3.0 in control subjects; p < 0.01). Neutrophil superoxide anion generation, measured as conversion of ferricytochrome C to ferrocytochrome C, in response to phorbol-12-myristate 13-acetate (100 ng/ml) was higher in hypertensive subjects (17.5 +/- 8.1 vs 13.2 +/- 3.0 nmoles/10(6) cells/10 minutes in control subjects; p < 0.05). Patients were treated with a selective beta blocker, celiprolol, for 8 weeks. Supine blood pressure decreased from 177/103 mm Hg (mean +/- SD 18/7) to 160/92 mm Hg (mean +/- 10/5; p < 0.02), while heart rate was unchanged (73 +/- 11 vs 69 +/- 10 beats/min). Epinphrine and adenosine diphosphate-induced platelet aggregation was also increased in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Simultaneous determination of verapamil and celiprolol in human plasma.

A simple and reproducible method for the simultaneous determination of the beta 1-selective adrenergic blocker, celiprolol, and the calcium antagonist, verapamil, in human plasma is described. It involves a two-step liquid-liquid extraction and separation using a C18 column with ultraviolet detection at 237 nm. Deacetyldiltiazem is used as the internal standard. Within-day and between-day coefficients of variation are less than 10%. The lower limits of detection are 4, 2, and 4 ng/mL for celiprolol, deacetyldiltiazem, and verapamil, respectively. The assay has clinical applicability.

Celiprolol↗

A double-blind evaluation of amlodipine in patients with chronic, stable angina: sustained efficacy and lack of "withdrawal phenomenon" upon abrupt discontinuation.

To date, the clinical utility of first-generation, shortacting calcium antagonists has not been optimal due to their multiple dosing requirements. This has led to poor compliance in some patients. In this study, the safety and efficacy of a new generation dihydropyridine calcium antagonist, amlodipine (5-10 mg once daily) were evaluated in patients with chronic, stable angina pectoris. Amlodipine monotherapy was given to 226 patients over an 8-week, single-blind period, and the responders (> or = 7% improvement in exercise time) then underwent a randomized, placebo-controlled, double-blind withdrawal phase, lasting for a further 4 weeks. Amlodipine was shown to be both effective and well-tolerated in patients with chronic, stable angina pectoris. There was no evidence for the development of tolerance to amlodipine over a total of 3 months and there did not appear to be any significant problems (of the type noted with abrupt beta-blocker cessation) associated with its withdrawal.

Amlodipine↗

High-performance liquid chromatographic determination of diltiazem and two of its metabolites in plasma using a short alkyl chain silanol deactivated column.

A simple and reproducible method for the determination of diltiazem and its two major metabolites, demethyl- and deacetyldiltiazem, is presented using a new column containing a short alkyl chain silanol deactivated support. This method involves the extraction of alkalinized plasma with a hexane-isopropanol mixture (95:5, v/v) followed by back-extraction into 5 mM sulfuric acid. Reversed-phase liquid chromatography is used with ultraviolet detection at 237 nm over a concentration range of 20-400 ng/ml for the compounds. Imipramine is used as the internal standard. Within-day and between-day coefficients of variation are less than 10%. The lower limits of detection are 4, 2 and 4 ng/ml for diltiazem, deacetyl- and demethyldiltiazem, respectively. Samples can be stored for up to thirty days with no significant degradation. The assay has clinical applicability.

Chromatography, High Pressure Liquid↗

Plasma concentrations and hemodynamic effects of intravenous, sublingual, and aerosolized nitroglycerin in patients undergoing cardiac catheterization.

Intravenous, sublingual, or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinically indicated cardiac catheterization. Eight blood samples were collected over 15 min from each patient, and analyzed for content of nitroglycerin, 1,2-glycerol dinitrate, and 1,3-glycerol dinitrate. Simultaneously, heart rate (HR), systolic blood pressure (SBP), and left ventricular end-diastolic pressure (LVEDP) were recorded. Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets. Metabolite concentrations were highest after intravenous injection at early time-points; at later time-points, no between-group differences could be detected. SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations. Minor fluctuations in HR were observed in association with all three formulations. LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form. Overall, no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin. Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent.

Administration, Inhalation↗

Double-blind evaluation of the dose-response relationship of amlodipine in essential hypertension.

To determine the dose-response efficacy of once-daily administration of placebo or a new long-acting calcium channel blocker amlodipine in patients with mild to moderate hypertension, a randomized, multicenter, placebo-controlled, double-blind trial was conducted. The study included 210 patients with diastolic hypertension (blood pressure 95 to 114 mm Hg) without major hematologic, renal, hepatic, cardiac, or endocrine abnormalities. After a 4-week single-blind placebo run-in period, patients were given placebo or amlodipine (1.25, 2.5, 5, or 10 mg) daily for 4 weeks. To assess the antihypertensive effect of amlodipine over a 24-hour period, blood pressure and pulse rate at weeks 0 and 4 were recorded for 12 hours after the dose and then again at 24 hours. At the end of the study patients treated with all doses of amlodipine greater than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing positions. Amlodipine, 1.25 mg daily, was also associated with a decrease in standing diastolic blood pressure. Response to treatment was greater in all amlodipine-treated patients than in those receiving placebo. Pulse rate in both the supine and standing positions was not significantly affected by amlodipine. At doses of 2.5, 5.0, or 10.0 mg daily, amlodipine maintained blood pressure below values obtained with placebo throughout the 24-hour period. Treatment with amlodipine was well tolerated and the incidence of side effects was low.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Isradipine--another calcium-channel blocker for the treatment of hypertension and angina.

OBJECTIVE: To review the pharmacology, pharmacokinetic disposition, dose recommendations, adverse effects, drug interactions, and efficacy of isradipine in patients with hypertension or ischemic heart disease. DATA SOURCES: Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: isradipine, calcium-channel blockers, hypertension, and angina pectoris. Experiences from studies evaluating isradipine reported in the form of articles, abstracts, or proceedings involving patients or healthy subjects were considered for inclusion. STUDY SELECTION: Special consideration was given to clinical studies that had been designed in a blind, randomized fashion. Studies that compared the effectiveness and safety of isradipine with another antihypertensive or antianginal agent or placebo were included. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were evaluated according to sample size, design, and adequacy of description of therapeutic response. DATA SYNTHESIS: Isradipine is a new dihydropyridine calcium-channel blocker that appears to exert less negative inotropic activity than nifedipine and to selectively inhibit sinoatrial conduction. Pharmacokinetic parameters are quite variable and considerably more work is needed to better describe the kinetic disposition of isradipine. Antihypertensive efficacy has been demonstrated extensively in a number of short-term trials. Antianginal efficacy also has been observed in a few short-term trials and is comparable to that of isosorbide dinitrate and nifedipine. Extensive experience with isradipine is minimal and no clear-cut advantages over existing compounds have been noted thus far. CONCLUSIONS: The place of isradipine in the therapy of hypertension and myocardial ischemia is unclear and its routine use cannot yet be recommended based solely on clinical grounds.

Angina Pectoris↗

Comparison of body mass indexes and cutoff points for estimating the prevalence of overweight in Hispanic women.

The anthropometric standards used for estimating the prevalence of overweight among Hispanic groups are generally developed in other populations. Our purpose was to identify appropriate anthropometric indicators and cutoff points for Hispanic women. Data from the Hispanic Health and Nutrition Examination Survey HHANES (1982-1984) included 1,784 Mexican American, 479 Cuban American, and 750 Puerto Rico women aged 25 to 74 years. The body mass indexes examined were weight/standing height1.5, weight/standing height2, weight/sitting height1.5, and weight/sitting height2. Appropriateness was based on correlation of the index with triceps and subscapular skinfold measurements and lack of association with standing or sitting height. The most appropriate indicator was weight/standing height2. To estimate overweight, the 85th percentiles for weight/standing height2 were obtained from the 20- to 29-year-olds in HHANES and the second National Health and Nutrition Examination Survey (NHANES II). For 10-year age intervals, the differences in proportions of women above those cutoff points were compared with a modified t test. The mean estimated prevalences of overweight were significantly higher with the NHANES II standard compared with the HHANES cutoff points (P < .05) for Mexican American women (43% vs 29%) and Puerto Rican women (40% vs 28%). They were slightly lower for the Cuban American women (36% vs 39%). Cutoff points are relative, not absolute, standards that must have biologic meaning. Before our results are used for assessing populations, the cutoff points should be tested for predictive validity with chronic disease rates.

Adult↗

Around the beta-blockers, one more time.

We review the pharmacology, pharmacokinetics, and relative costs of beta-blockers, as well as indications for and therapeutic controversies surrounding their use. It is hoped that this discussion will assist clinicians in making informed decisions when choosing a drug for a hospital formulary or a particular patient. Beta-blockers are indicated for a variety of noncardiovascular and cardiovascular conditions, including hypertension, ischemic heart disease, arrhythmias, and prophylaxis of myocardial infarction (MI). These agents compete with catecholamines at beta-adrenoreceptors. They have different ancillary properties, including intrinsic sympathomimetic activity (ISA), cardioselectivity, and membrane stabilizing-activity, and vary in their duration of action, route of elimination, and lipophilicity. Beta-blocking agents decrease oxygen demand by exerting a negative inotropic and chronotropic effect. They also reduce blood pressure and possess antiarrhythmic effects. Beta-blockers penetrate the central nervous system (CNS) to different degrees and can cause a wide variety of CNS adverse effects. Nonselective beta-blockers have been noted to slightly reduce renal blood flow. Nadolol is an exception in that either no change, or even a small increase in renal blood flow, is observed upon initiation of therapy. Beta-blockers also act on the pulmonary bed by preventing beta 2-mediated bronchodilation, thereby exacerbating bronchospastic disease in some patients. Beta-adrenergic blocking agents can potentiate both hypoglycemia and hyperglycemia in diabetic patients. Their effects on total peripheral resistance (TPR) are controversial. Initially it appears that beta-blockade increases TPR. After chronic therapy, however, TPR decreases to or below baseline values. These agents appear to be equally efficacious in the treatment of hypertension, arrhythmias, and ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Felodipine: a new dihydropyridine calcium-channel antagonist.

Felodipine, a dihydropyridine calcium-channel antagonist, significantly reduces systolic and diastolic blood pressure (BP) in patients with hypertension and has been associated with beneficial hemodynamic effects in patients with chronic stable angina pectoris or congestive heart failure (CHF). In hypertensive patients, felodipine does not appear to significantly affect glomerular filtration rate, creatinine clearance, glucose tolerance, or plasma lipoprotein concentrations. Studies comparing felodipine with other agents as monotherapy in mild to moderate hypertension have demonstrated felodipine to be at least as efficacious as hydrochlorothiazide (HCTZ) and HCTZ plus amiloride hydrochloride in combination. Comparisons of felodipine with other agents as adjuncts to beta-blocker or diuretic therapy have shown felodipine to be at least as effective as HCTZ, propranolol hydrochloride, prazosin hydrochloride, and nifedipine. Evaluations of patients with chronic stable angina are limited, and additional studies are needed before felodipine can be recommended for the routine management of angina pectoris. Similarly, additional studies are essential to delineate the role of felodipine, if any, in the management of CHF. In the management of hypertension, felodipine 5-40 mg/d significantly reduces systolic and diastolic BP. Although some patients may be controlled throughout the entire dosing interval when felodipine is administered bid, many patients will require more frequent dosing to obtain adequate BP control. Adverse effects associated with felodipine are similar to those of other dihydropyridine calcium-channel antagonists and include peripheral edema, headache, dizziness, flushing, and fatigue. A potentially clinically important drug interaction was observed when felodipine was administered concomitantly with theophylline aminopropanol; significant decreases in theophylline concentrations were noted. In summary, felodipine appears to be safe and effective for the management of hypertension when used alone or in combination with other antihypertensive agents. The efficacy of felodipine in the management of chronic stable angina pectoris and CHF requires further investigation.

Angina Pectoris↗

Cost-effective implementation of clinical pharmacy services in an ambulatory care clinic.

Implementation of clinical pharmacy services in the current economic environment of the health care system requires cost justification of the service in addition to quality patient care services. Herein described is the evaluation of the cost effectiveness of a clinical pharmacy service implemented in an ambulatory care clinic of a regional Veterans Administration Medical Center. This evaluation assessed the ability of a clinical pharmacist to decrease the prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs) by clinic physicians. Through analysis of prescription data prospectively collected for a period of 18 months, average cost of NSAIDs both before and after initiation of a clinical pharmacy presence was evaluated. A comparison was made between Evaluation Clinic providers (EC) and all other ambulatory care providers (OAC). The decrease in the average cost/prescription of NSAIDs for EC and OAC was 23.4% and 5.2% (P less than 0.005), respectively. This decrease was associated with a net annual savings in drug costs of $38,776. This single intervention cost-justified a clinical pharmacist's position.

Anti-Inflammatory Agents, Non-Steroidal↗

Hypertension in the elderly: conventional wisdom revisited.

Elevated systolic and/or diastolic blood pressure in the elderly is a problem the extent of which may be somewhat overstated. In those elderly with definite hypertension, pathophysiology may differ from that of younger counterparts. The contribution of elevated plasma renin activity to hypertension and to the choice of therapy also appears to be exaggerated. The risks of ignoring hypertension in the elderly are similar to those in younger patients, and therefore excessively elevated blood pressure should no longer be considered a normal consequence of aging. Notably, elevated systolic pressure is a better predictor of future adverse occurrences than is elevated diastolic pressure. Unfortunately, there is no well defined therapeutic regimen to manage isolated systolic hypertension. Conservative reduction of elevated systolic and diastolic pressures may nevertheless be accomplished safely and effectively. Individualization of therapy is recommended based primarily on concomitant disease(s). Thus no single agent or combination of agents is preferable in all elderly hypertensive patients. Aggressive use of non-pharmacologic therapy preferably precedes judicious of antihypertensive medication. Aggressive blood pressure reduction with potent drugs is not recommended.

Adrenergic beta-Antagonists↗

Simultaneous determination of propranolol and 4-hydroxypropranolol enantiomers after chiral derivatization using reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method is described, which allows the simultaneous quantification of propranolol and 4-hydroxypropranolol enantiomers in human plasma. After extraction from plasma (pH 10.5) using ethyl acetate, the enantiomers are derivatized with R-(+)-phenylethylisocyanate as chiral derivatization reagent and triethylamine as basic catalyst in chloroform. Ascorbic acid is used to prevent 4-hydroxypropranolol from oxidation during the extraction. Chromatographic separation on ODS columns and fluorescence detection (228 nm/greater than 340 nm) allows sensitive quantitation of all derivatives. Incubation of the plasma samples with beta-glucuronidase/arylsulfatase and the use of the specific beta-glucuronidase inhibitor saccharo-1,4-lactone allows the quantitation of both the sulfate and glucuronide conjugates of the enantiomers. The method was applied to human plasma samples from a subject after administration of 60 mg racemic propranolol three times daily.

Animals↗