Disease relevance of Chlorphthalidolone

• INTERVENTIONS--Subjects were randomly assigned to usual, weight loss, or low sodium/high potassium diet and then randomly assigned to receive placebo, chlorthalidone, or atenolol [1].
• Incidence of chlorthalidone-induced hypercalcemia [2].
• Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years [3].
• Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups [3].
• Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats [4].

Psychiatry related information on Chlorphthalidolone

• Nevertheless, chlortalidone and other diuretics have been more often associated with sexual dysfunction in men, including decreased libido, erectile dysfunction and difficult ejaculation, than other drug classes [5].
• Results confirm that the fixed combination of oxprenolol 160 mg slow-release + chlorthalidone 20 mg is able to long term control mild to moderate hypertension with a good tolerability, thus allowing an improved patient compliance [6].

High impact information on Chlorphthalidolone

• Chlorthalidone in hypoparathyroidism [7].
• INTERVENTIONS.- Participants were randomized to 1 of 6 treatment groups: (1) placebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodipine), (4) diuretic (chlorthalidone), (5) alpha1-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril) [8].
• In the latter, chlorthalidone significantly increased total serum cholesterol (13%, p less than 0.001), low-density-lipoprotein (LDL) cholesterol (21%, p less than 0.001) and apoprotein B (16%, p less than 0.05) [9].
• However, within the normal PRA EHT subgroup receiving chlorthalidone, the one-third of patients with lowest pretreatment DBH levels (n = 10) were compared with the one-third of patients with the highest pretreatment DBH values (n = 10) [10].
• The odds ratios for developing DM with lisinopril (0.55 [95% confidence interval, 0.43-0.70]) or amlodipine (0.73 [95% confidence interval, 0.58-0.91]) vs chlorthalidone at 2 years were significantly lower than 1.0 (P<.01) [11].

Chemical compound and disease context of Chlorphthalidolone

• Group A: In 14 patients with essential hypertension on chlorthalidone treatment, an additional daily dose of 640 mg propranolol for two months led to a significant reduction of the MAP (from 124 to 105 mm Hg) and PRA (from 5.3 to 2.0 ng AI/ml/hr standing) [12].
• Once-daily low-dose hydrochlorothiazide (12.5 mg/ day) or chlorthalidone (15 mg/day) effectively reduces blood pressure in patients with stage 1 or stage 2 hypertension in comparison with placebo [13].
• In 79 patients with essential hypertension, treatment with propranolol hydrochloride and chlorthalidone together produced significantly greater falls in both systolic and diastolic blood pressures than were obtained with either drug alone [14].
• Metoprolol with and without chlorthalidone in hypertension [15].
• Guanfacine, 1 to 3 mg/day, and clonidine, 0.1 to 0.3 mg twice a day, were compared in a 24-week double-blind, randomized, parallel study of 42 patients with hypertension that was inadequately treated by chlorthalidone, 25 mg/day [16].

Biological context of Chlorphthalidolone

• Blood pressure reductions with low-dose hydrochlorothiazide and chlorthalidone are comparable to that achieved with higher doses (25 and 50 mg/day) [13].
• Atenolol and chlorthalidone on blood pressure, heart rate, and plasma renin activity in hypertension [17].
• OBJECTIVE: The alpha 1-adrenoreceptor blocker doxazosin, which in the ALLHAT trial was associated with a greater risk of heart failure than the diuretic chlorthalidone, induces the apoptosis of human and murine cardiomyocytes regardless of alpha 1-adrenoreceptor blockade [18].
• Thus, chlorthalidone and acetazolamide were able to displace indapamide from erythrocytes in vitro and in vivo, possibly by competition at a carbonic anhydrase binding site [19].
• Pharmacokinetics of chlorthalidone in the elderly after single and multiple doses [20].

Anatomical context of Chlorphthalidolone

• The affinity of chlorthalidone for red blood cells was further evidenced on incubation of 14C-chlorthalidone with human blood [21].
• Preincubation of the blood samples with acetazolamide prior to the addition of 14C-chlorthalidone, as well as incubation of acetozolamide in blood samples previously incubated with 14C-chlorthalidone, demonstrated that acetazolamide is able to inhibit and to displace chlorthalidone from blood cells [21].
• Thus, myocardial electrical excitability was measured in patients with mild essential hypertension and known coronary artery disease after 8 weeks of treatment with a potassium-conserving diuretic (amiloride) and a similar period on a potassium-losing diuretic (chlorthalidone) in a randomised study [22].
• Non-use of chlorthalidone was associated with bone loss at the calcaneus (-0.56% per year) and the proximal radius (-0.91% per year); borderline bone gain was observed at the distal radius (+0.39%) [23].
• In 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment, the effect of 2 weeks of additional therapy with the converting enzyme inhibitor (CEI) enalapril on blood pressure and body fluid volumes has been evaluated [24].

Associations of Chlorphthalidolone with other chemical compounds

• Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone (25 mg) and triamterene (50 mg) and the beta-blocker oxprenolol (160 mg) and the greater efficacy of the combination of the two therapies [25].
• In a second trial, 12 hypertensive patients not adequately controlled by chlorthalidone 25 mg daily as monotherapy (supine diastolic blood pressure at rest greater than 95 mm Hg), continued the diuretic treatment in combination with captopril, 25 mg t.i.d. and 25 mg b.i.d. according to a randomized within-patient open design [26].
• Qualitative urinary chlorthalidone and hydrochlorothiazide levels and changes in serum potassium, uric acid, and blood pressure also correlated with pill count compliance but were less accurate than interviews [27].
• Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group [28].
• Of the 15 patients treated with chlorthalidone, 14 had satisfactory reduction in diastolic pressure compared with only four of the 14 treated with clonidine [29].

Gene context of Chlorphthalidolone

• Effects of antihypertensive agents propranolol, metoprolol, nadolol, prazosin, and chlorthalidone on ACAT activity in rabbit and rat aortas and on LCAT activity in human plasma in vitro [30].
• There are several lines of evidence indicating that chlorthalidone is transported attached to the erythrocyte carbonic anhydrase [21].
• Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication [31].
• Chlorthalidone, given to seven patients with renal IHC during 4 weeks (100 mg/day), did not decrease the PTH levels [32].
• Six classes of drugs were studied: (1) acebutolol (beta blocker), (2) amlodipine (calcium antagonist), (3) chlorthalidone (diuretic), (4) doxazosin (alpha 1 antagonist), (5) enalapril (angiotensin-converting enzyme inhibitor) and (6) placebo [33].

Analytical, diagnostic and therapeutic context of Chlorphthalidolone

• Oral chlorthalidone plus a low salt diet appears to be an effective alternative to vitamin D in the maintenance therapy of at least some patients with hypoparathyroidism [34].
• Efficacy and reduced metabolic side effects of a 15-mg chlorthalidone formulation in the treatment of mild hypertension. A multicenter study [35].
• CONCLUSION: In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men [36].
• Two consecutive 24-h urine collections were obtained after a baseline period and after 2 wk of chlorthalidone (25 mg), amiloride (5 mg), and the two diuretics in combination, with a week off drug separating the treatment periods in a randomized crossover design [37].
• Two long-term clinical trials using low-dose (12.5-15 mg/day) chlorthalidone-the Systolic Hypertension in the Elderly Program (SHEP) and the Treatment of Mild Hypertension Study (TOMHS)-were also included [38].

References