ABSTRACT
The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations.
Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Antihypertensive Agents/therapeutic use , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Lipids/blood , Prazosin/analogs & derivatives , Adrenergic alpha-Antagonists/adverse effects , Adult , Aged , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Clinical Trials as Topic , Double-Blind Method , Doxazosin , Female , Heart Rate/drug effects , Humans , Hydrochlorothiazide/adverse effects , Hypertension/blood , Male , Middle Aged , Prazosin/adverse effects , Prazosin/therapeutic use , Prospective Studies , Random AllocationABSTRACT
The primary aim of this study was to compare task performance in a laboratory test and real driving performance of outpatients receiving diazepam medication with those of control subjects. Plasma and saliva samples were taken to investigate a level-response relationship. Real driving performance was measured by trained observers. The design of the laboratory test was based on a vigilance task (high attention) directly followed by a simple eye-hand coordination tasks (low attention). Twenty-two males participated in the study. Diazepam was given orally by prescription, mostly as a maintenance dose of 5 mg three times a day. Patients receiving diazepam showed impaired performance in the driving test and the low-attention task. Furthermore, the results indicate no relationship between plasma or saliva levels of diazepam and/or its metabolite N-desmethyldiazepam and real driving performance and/or laboratory task performance.
Subject(s)
Attention/drug effects , Automobile Driving , Diazepam/adverse effects , Adult , Diazepam/analysis , Diazepam/blood , Dose-Response Relationship, Drug , Humans , Male , Middle Aged , Outpatients , Saliva/analysis , Visual Perception/drug effectsABSTRACT
1. Salivary, unbound and total plasma levels of diazepam have been compared in nineteen subjects. 2. Salivary diazepam levels were significantly higher (P < 0.001) than, but closely related to the corresponding unbound levels (r = 0.97) at 2.5-3 h after administration of the drug. 3. The results presented suggest that saliva levels can be used to predict the corresponding plasma levels at a given time, but there is no 1:1 relation between the unbound diazepam concentration in plasma and the saliva level of the drug.
