ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (All-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to All-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A1e(HbA1e) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the All-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 ± 5 mm Hg (P<.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 ± 5.0 mL/100 mL tissue/min (P<.001), and HbA1eincreased by 0.6 ± 0.8 mmol/L (P<.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA1e, the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA1eand MAP was no longer significant. Replacement of ACE-i by All-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA1eand MAP and a decrease in FLOW. The associations of HbA1eand FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin2-receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Dolasetron mesylate (MDL 73,147, Anzemet, Hoechst Marion Roussel, Kansas City, MO) is a 5-HT3receptor antagonist undergoing clinical evaluation as an antiemetic agent. Dolasetron is rapidly metabolized to form hydrodolasetron (MDL 74,156). The pharmacokinetics of hydrodolasetron were studied after administration of a single intravenous infusion of 0.6 mg/kg (group I) or 1.8 mg/kg (group II) in 21 cancer patients participating in a randomized, double-blind, parallel-group, multicenter trial of the drug in patients receiving their first course of high-dose (>75 mg/cm2) cisplatin-containing chemotherapy. The intent of this study was to obtain preliminary data on the pharmacokinetics of the active metabolite, hydrodolasetron, in cancer patients. The reduced metabolite, hydrodolasetron, was formed rapidly with peak plasma concentrations (group I, mean = 128.6 ng/mL; group II, mean = 505.3 ng/mL) occurring at or shortly after the end of the infusion. Plasma concentrations of hydrodolasetron remained quantifiable for up to 24 hours. Increases in peak plasma concentrations and AUC of hydrodolasetron were proportional to dose, suggesting linear pharmacokinetics over this dose range. Apparent clearance, apparent volume of distribution, elimination rate, and terminal elimination half-life of the reduced metabolite were similar at both doses. The results support a pharmacokinetic basis for the prolonged duration of antiemetic efficacy after a single intravenous dose.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

This was a double-blind, randomized, two-center, active-controlled, prospective, parallel study designed to evaluate the effects of nebivolol at daily doses of 5 mg on lipid and carbohydrate metabolism and on blood pressure in comparison with atenolol at daily doses of 50 mg. Normometabolic subjects with mild-to-moderate essential hypertension were recruited for this study, which included a 4-week, single-blind placebo washout phase and a 12-week double-blind treatment phase. After 12 weeks of treatment, both drugs demonstrated a significant decrease from baseline in high-density lipoprotein (HDL) apolipoprotein A-I (HDL-apoA-I) (nebivolol,P<.02; atenolol,P<.05). A significant reduction in HDL cholesterol (HDL-C) from baseline was also observed with nebivolol (P<.05). There were no significant differences between the drugs for these parameters, and the ratio low-density lipoprotein cholesterol (LDL-C)-to-HDL-C did not change significantly after 12 weeks of active treatment with nebivolol or atenolol. There were no significant changes in total cholesterol, HDL2-C, HDL3-C, LDL-C, very-low-density lipoprotein cholesterol (VLDL-C), total triglycerides, HDL-triglycerides (TG), LDL-TG, VLDL-TG, total apoB, LDL-B, VLDL-B (including the ratio LDL-C-to-LDL-apoB), or Lp(a) during treatment with both drugs. No significant differences in plasma apoA-I and apoC-III as well as in apoA-I-, C-III-containing lipoprotein particles (including the apoC-III ratio) were observed between the drugs, neither before nor after each active treatment. There were no significant differences between the drugs or within each treatment group in plasma glucose, insulin, or C-peptide concentrations after a 2-hour oral glucose tolerance test. Mean clinic trough sitting systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 150/98 mm Hg at baseline to 141/90 mm Hg at termination for nebivolol and from 160/99 mm Hg at baseline to 145/88 mm Hg at termination for atenolol. No significant between-treatment differences were observed for the mean clinic trough sitting SBP/DBP. Both drugs significantly increased the atrial natriuretic factor (ANF) N-terminal plasma levels, whereas no changes were observed in ANF C-terminal plasma concentrations. A significant decrease (P<.05) in the plasma adrenocorticotropic hormone levels was observed after administration of both drugs. A significant decrease (P<.05) in plasma cortisol levels was observed only after atenolol treatment. The incidence of adverse events reported during nebivolol treatment was comparable to that observed during atenolol treatment. Heart rate was significantly reduced by both drugs. There were no significant changes in hematology, biochemistry, or urinalysis studies. Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients. Both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Antihistamines are the pharmacologic cornerstone of treatment for allergic rhinitis. The comparative effects of the newer, more specific H1-antagonists cetirizine and loratadine among younger patients are not well characterized. The efficacy and safety of cetirizine and loratadine were compared in a prospective, randomized, double-blind, longitudinal, parallel-group study of 80 children, 2 to 6 years of age, with perennial allergic rhinitis caused by house dust mites or plant pollens (verified by a radioallergosorbent or skin test). Patients received cetirizine or loratadine at 0.2 mg/kg once daily in the morning for 28 days. Histamine skin tests and eosinophil counts from nasal smears were performed at a baseline and at the end of treatment. Individual rhinitis symptoms were assessed by the investigator at baseline and on day 28 and by parents at baseline and daily in symptom diaries. Global assessments were made by using a visual analog scale at baseline and at the end of treatment. Cetirizine produced significantly greater inhibition of the wheal response compared with loratadine (P< .0001). Eosinophil counts were improved to a comparable degree with both agents. Cetirizine and loratadine produced comparable improvements in symptoms and according to a global evaluation as assessed by the investigator at the end of treatment. Both agents produced substantial symptomatic relief according to patients' daily diary assessments; however, cetirizine was more effective than loratadine in relieving the symptoms of rhinorrhea, sneezing, nasal obstruction, and nasal pruritus (P< .0001). Both treatments were well tolerated; two patients receiving cetirizine were dropped from the study because of adverse events. Cetirizine and loratadine provided effective, well-tolerated relief of the symptoms of perennial allergic rhinitis in small children. Cetirizine was more effective than loratadine in inhibiting the wheal response to histamine challenge and afforded greater reductions in most individual symptoms assessed daily by the parent.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 ± 6 years. The elimination half-lives at β-phase averaged 25.0 ± 16.4 hours, the volume of distribution averaged 32.9 ± 13.4 L, and the total clearance averaged 1.14 ± 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was .54 (P= .06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

In this study, telmisartan, a new angiotensin AT, receptor antagonist given as monotherapy and in combination with hydrochlorothiazide (HCTZ), was compared with lisinopril as monotherapy and in combination with HCTZ. This 52-week, randomized, multicenter, double-blind, double-dummy, parallel-group, dose-titration study of 578 patients with mild-to-moderate essential hypertension (mean diastolic blood pressure [DBP], >95 mm Hg), compared the efficacy and safety of telmisartan (n = 385) with lisinopril (n = 193). Dosage could be increased for both telmisartan (40 → 80 → 160 mg) and lisinopril (10 → 20 → 40 mg) at each of the first 2 monthly visits if DBP control (<90 mm Hg) had not been established. Once DBP control was established, patients entered the 48-week maintenance period. During this period, the dose of the study drug was fixed, although open-label HCTZ at 12.5 mg or 25 mg was added, when needed, to regain DBP control. At the end of the titration period, DBP control was achieved on monotherapy by 67% and 63% of the telmisartan and lisinopril patients, respectively. At the end of the maintenance period, supine DBP was controlled in 83% and 87% of the telmisartan and lisinopril patients, respectively, with systolic blood pressure over DBP reductions of 23.8/16.6 mm Hg for telmisartan and 19.9/15.6 mm Hg for lisinopril. Treatment-related side effects occurred in fewer telmisartan-treated patients (28%) than in lisinopril-treated patients (40%;P= .001). Significantly fewer patients (P= .018) receiving telmisartan experienced treatment-related cough (3%v7%), and cough led to discontinuation significantly less often (P= .007) with telmisartan treatment than with lisinopril treatment (0.3%v3.1%). In addition, two cases of angioedema were observed, both in the lisinopril group. The selective AT1receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

There has been much interest in the effect of sex hormones on cardiovascular risk factors and as a therapeutic modality in both men and women. In this article, testosterone is considered as a possible therapy for cardiovascular disease. It has been shown that the level of serum testosterone decreases in men as they age. Healthy men with low testosterone levels have increased cardiovascular risk factors, including high fasting and 2-hour plasma glucose, serum triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol, and apo A-l lipoprotein. Injections of testosterone to raise the levels to midnormal range have been shown to decrease total cholesterol and I.DL cholesterol, while increasing high-density lipoprotein (HDL) cholesterol. Testosterone affects the clotting system by increasing thromboxane A2receptor activity and platelet aggregability. Testosterone has also been shown to augment the fibrinolytic system and antithrombin III activity. In men, testosterone has been shown to have antianginal effects, and endogenous levels have an inverse relationship to systolic blood pressure. Testosterone can be given in oral, injectable, pellet, and transdermal patch forms. There may be a role in administering testosterone to return men to normal physiologic range who have low serum levels. This treatment increases the risk of prostatic cancer, benign prostatism, erythrocytosis, and edema. No long-term studies of the effects of long-term testosterone replacement have been undertaken, so it is difficult to recommend this treatment as yet, but it is being considered as a therapy for augmenting skeletal muscle strength in patients with congestive heart failure.

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1075-2765    

出版商:OVID    

年代:1999

数据来源: OVID