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[Administration of cardiac agents, antihypertensive agents, beta receptor blockers, coronary therapeutic agents and diuretics to patients with newly detected type II diabetes].

In 210 newly detected untreated diabetics of type IIA or B from 4 districts of the county of Neubrandenburg who were admitted to hospital in 1982 their behaviour in taking medicaments was analysed. Cardiac remedies strictly speaking and in the wider sense were classified into the drug groups cardiac remedies (glycosides), antihypertensive agents, beta-receptor blockers, other coronary therapeutic agents and diuretics. At the same time the prevalence of the cardiovascular risk signs overweight (75.7%), hypertension (69.1%), hypertriglyceridaemia (54.8%), hypercholesterolaemia (43.3%), hyperuricaemia (21.0%) and inhalation of cigarette smoke (greater than or equal to 5 cigarettes a day: 12.9%) was established. The proportion of obese persons diminished with growing age, also the percentage of smokers was in the same proportion. In the inverse ratio to this the proportion of diabetics with hyperuricaemia increased according to age. 62.9% of the newly detected diabetics were treated with cardiac glycosides and 49.1% with antihypertensive agents. Only every 4th to 5th patient did not receive a medicament from the drug groups investigated. With the exception of the cardiac remedies in all other groups of substances the proportion of patients treated increased with the enlarging number of cardiovascular risk signs.

Adrenergic beta-Antagonists↗

[Blood pressure independent effects of antihypertensive agents].

Antihypertensive medications belong to different pharmacological classes. Besides blood pressure lowering properties, many substances, particularly ACE inhibitors and AT1-receptor antagonists but also in part calcium antagonists and aldosterone receptor antagonists, exert additional anti-inflammatory and antifibrotic effects as well as protective effects on endothelium. Delay of disease progression in chronic kidney disorders by inhibition of the renin-angiotensin system also as the result of blood pressure independent effects has been documented in clinical trials. On the other hand, in patients with essential hypertension without end-organ damage, it remains unclear whether the clinically proven blood pressure independent effects of antihypertensive agents are also clinically relevant. However, in clinical studies ACE inhibitors and AT1-receptor antagonists reduce the de novo occurrence of the diabetic metabolic state. Inhibition of the renin-angiotensin system decreases the incidence of diabetic nephropathy. This contribution presents currently available data on possible blood pressure independent effects of antihypertensive agents.

Antihypertensive Agents↗

Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect.

Tamsulosin, an alpha 1A-adrenoceptor antagonist, has recently been approved to treat patients with symptomatic benign prostatic hyperplasia (BPH). Tamsulosin is highly selective for prostatic receptors with minimal affinity for vascular receptors. Therefore, it should have little effect on blood pressure and should not potentiate other agents' antihypertensive activity. To test this hypothesis, we conducted three randomized, double-masked, placebo-controlled studies to evaluate how coadministration of tamsulosin would affect the pharmacodynamic profiles of nifedipine, enalapril, and atenolol. Each study enrolled 12 hypertensive men aged 45 years or older whose blood pressure was being controlled with maintenance doses of nifedipine (study 1), enalapril (study 2), or atenolol (study 3). All 36 subjects were treated with placebo for 5 days and then randomly assigned to either placebo (control group) or tamsulosin therapy (0.4 mg/d for 7 days followed by 0.8 mg/d for 7 days) in addition to continuing their maintenance antihypertensive therapy. Blood pressure and pulse rate were monitored over a 24-hour period on study days 4, 11, and 19. Coadministration of tamsulosin in these small studies had no clinically significant effects on the pharmacodynamic action of nifedipine, enalapril, or atenolol; it produced no clinically significant differences in pulse rate and blood pressure, did not alter electrocardiographic or Holter monitoring results, and did not cause increased side effects. Coadministration of tamsulosin with the three antihypertensive agents studied had a favorable safety profile. Our results in these small studies indicate that the dose of nifedipine, enalapril, or atenolol did not require adjustment in patients given tamsulosin, which may give tamsulosin an advantage over other alpha-blocking agents used to treat patients with BPH. Now that tamsulosin has been approved in the United States, further clinical use may confirm these findings.

Adrenergic alpha-Antagonists↗

Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure, 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean, -42.9; 95% confidence limits, -65.5, -20.2 g), captopril (mean, -38.7; 95% confidence limits, -61.0, -16.4 g), and atenolol (mean, -28.1; 95% confidence limits, -50.9, -5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. CONCLUSIONS: Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.

Adrenergic alpha-Antagonists↗

New class of antihypertensive agents.

Effective antihypertensive agents of the benzothiadiazine series, devoid of diuretic activity, are described. There follows a method of synthesis and a description of the pharmacological activity of one of these substances

Antihypertensive Agents↗

Rapid-acting parenteral antihypertensive agents.

Parenteral antihypertensive agents are useful in those clinical situations where rapid reduction of blood pressure is necessary or where treatment with oral antihypertensive medications is not feasible. Given the diverse selection of parenteral antihypertensive drugs now available, therapy can be individualized. The presence of concurrent diseases will often influence the decision-making process regarding choice of an agent. Complications of parenteral antihypertensive therapy can arise from the intrinsic properties of the various drugs or the development of severe hypotension. Gradual lowering of blood pressure, in conjunction with careful clinical evaluation, will minimize the risks of acute parenteral antihypertensive therapy. Given that parenteral antihypertensive therapy often needs to be replaced by oral therapy, those drugs that can be used both parenterally and orally may have an advantage.

Antihypertensive Agents↗

The behavioral side effects of the antihypertensive agents.

Most antihypertensive agents can cause behavioral side effects but only a few effects, such as delirium or severe depression, are serious enough to dictate immediate discontinuance of the offending agent. Other side effects may not even be mentioned by the patient but they can alter the quality of life and, as a result, alter compliance with treatment. For example, sexual difficulties may not be mentioned because of embarrassment. Alteration in dosage, a change in the time of administration or a change to alternative medication may alleviate these problems and help restore the patient's compliance with treatment.

Antihypertensive Agents↗

Liquid chromatographic separation and UV determination of certain antihypertensive agents.

Three antihypertensive agents were extracted and isolated from commercial formulations. These were purified and characterized by melting point, lambdamax and IR. The percentage recovery by extraction process was in the range 81-91%. Active ingredients from binary formulations were separated by RP-HPLC using methanol-water (50:50 v/v) and by TLC using CHCl3-CH3OH (6:1) as mobile phase. Detection was by UV at 210 nm in HPLC, and by iodine vapors in TLC. The solvent conditions from TLC were transferred to open column chromatographic separation. Quantitative determination was carried out using TLC and column chromatography supplemented with UV spectrophotometry. Recovery was in the range 82-93%. Two combination of drugs, viz. amlodipine+ramipril and amlodipine+enalapril, were separated by the three modes of liquid chromatography. The percentage recovery was in the range 80-92% by open column.

Amlodipine↗

Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors. METHODS: In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS: The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks (< 60 years) and older blacks (> or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. CONCLUSIONS: Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.

Age Factors↗

Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.

Adult↗

Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents.

A series of N-[(1H-heteroaryl)alkyl]-1H-isoindole-1,3(2H)-diones were prepared as part of a continuing investigation into the biological properties of compounds that were both thromboxane synthetase inhibitors and potential antihypertensive agents. The most active thromboxane synthetase inhibition was found for the title imidazole derivatives wherein a hexyl or octyl chain separated the heterocyclic ends of the molecule (5,6) or with substitution on the isoindole portion of the molecule (18, 19, 21, 22, 25, 26). Compounds with shorter alkyl chain separations had good antihypertensive effects (1-5, 8-10, 19-22, 27-30). Butyl derivative 3 was chosen for further evaluation as a potential antihypertensive agent with thromboxane synthetase inhibitory properties.

Animals↗