Effect of Repeated Doses of Hydroflumethiazide on Renal Excretion of Electrolytes and Uric Acid in Healthy Subjects

Abstract: Urinary excretion of electrolytes and uric acid was investigated in six healthy subjects during repeated oral administration of 100 mg hydroflumethiazide (HFT) daily for seven days, and related to urinary thiazide excretion. Mean 24 hr-urinary excretion of sodium and chloride increased 100% (P<0.02) after the first HFT-dose, whereas 24 hr-excretion values were at control level after the fourth and seventh doses. Mean 24 hr-urinary excretion of potassium was increased by 31% after the first HFT-dose (P<0.05) and by 47% after the fourth dose (P <0.05). After HFT was discontinued, mean urinary excretion rates of sodium and chloride dropped to 30% and that of potassium to 70% of control. In the state of fluid deficiency and elevated aldosterone concentration, there was a significant positive correlation between log excretion rate of HFT and excretion rate of sodium (r=0.68, P<0.002) calculated from excretion data 0–6, 6–12, and 12–14 hrs after the seventh dose. After the first dose of HFT, sodium excretion was also significantly correlated to log excretion rate of HFT (r=0.86, P<0.001) but was probably influenced by other factors as well. Mean serum concentration of uric acid increased significantly, but mean 24 hr-urinary excretion of uric acid was constant during HFT-treatment.     

Ace inhibitors compared with thiazide diuretics as first-step antihypertensive therapy

Summary While ACE inhibitors are considerably more expensive than thiazide diuretics, they are slightly more effective antihypertensive agents in white patients and have fewer side effects. They can be regarded as suitable first-line therapy in diabetic hypertensives. It is probable that as new drugs in this class are marketed, the price differential will lessen and they will be regarded as acceptable and useful first-line drugs in an increasingly large number of patients.     

Reduced high density lipoprotein in stroke: relationship with elevated triglyceride and hypertension

Lipids and lipoproteins were analysed in forty-one survivors of stroke, aged less than 65 years, and the same number of age and sex matched controls without vascular disease. The stroke subjects had no evidence of coronary artery or peripheral vascular disease. High density lipoprotein cholesterol was significantly lower (1.19 +/- 0.06 mmol/l) in the stroke subjects than the controls (1.47 +/- 0.07 mmol/l). Triglyceride was also elevated in the stroke subjects, but this was confined to those who were taking antihypertensive treatment which included beta-blockers and/or thiazides. The low levels of high density lipoprotein in stroke were independent of hypertension or its treatment. Thus low levels of high density lipoprotein appear to be associated with cerebrovascular disease, while elevated triglyceride is a complication of anti-hypertensive therapy.     

Diuretics in the treatment of hypertension

Diuretics are powerful agents that impair sodium reabsorption in renal tubules. Their ability to alter long-term sodium balance induces important hemodynamic changes that result in a reduction in peripheral resistance and sustained reduction in blood pressure. A pharmacologically diverse group of drugs, they remain a mainstay in the therapy of hypertension. Clinical trials over the past 4 decades consistently have shown that blood pressure lowering obtained from a diuretic-based regimen reduces cardiovascular events. The ability of diuretics to augment the efficacy of nearly all other classes of antihypertensives makes them highly versatile and an important pharmacotherapeutic intervention to achieve blood pressure control. This article reviews key aspects of the use of diuretics relevant to the clinical management of hypertension.     

Gallbladder disease in the general population: association with cardiovascular morbidity and therapy

PURPOSE: Both gallbladder (GB) and cardiovascular disease are very common diagnoses that carry substantial economic costs. Prior studies suggest that personal history of ischaemic heart disease (IHD) could determine the occurrence of GB disease. Additionally the use of thiazide diuretics may also be a risk factor for this condition. We aimed to evaluate different cardiovascular conditions and related drugs that could be associated with GB disease. METHODS: We identified all incident cases of gallbladder disease occurring during 1996 among patients aged 20-79 years old registered in the General Practitioner Research Database. We performed a nested case control analysis using 2353 cases and 10,000 controls frequency matched to the cases by age and sex. RESULTS: After adjusting for potential confounders IHD was associated with a small increased risk of GB disease (1.29, 95%CI:1.08-1.55). When only cases requiring cholecystectomy were considered in the analysis, the resulting estimate was 1.06 (95%CI:0.83-1.35). Users of thiazide diuretics presented an OR of 1.36 (95%CI:1.08-1.71). Other antihypertensive drugs were not associated with GB disease. CONCLUSIONS: Our results confirm the small increased risk of GB disease associated with thiazide diuretics. On the other hand, our data do not support a major association between IHD and GB disease.     

Extrarenal roles of the with‐no‐lysine[K] kinases (WNKs)

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Relation Between Low Dose of Hydrochlorothiazide, Antihypertensive Effect and Adverse Effects

Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ. To characterize the lower end of the dose-response curve a double-blind, parallel group trial was performed as multicentre study in Scandinavia. One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension (untreated diastolic blood pressure of 95-115 mmHg after 4 weeks placebo) were randomly allocated to various doses of hydrochlorothiazide (3, 6, 12.5 or 25 mg) or placebo for 6 weeks. Blood pressure and biochemical variables (plasma renin activity, serum potassium, magnesium, urate, fasting glucose, total cholesterol, HDL-cholesterol, triglycerides and apolipoproteins A1 and B were measured. 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect. Biochemical changes were seen in plasma renin activity, serum potassium and urate after the 12.5 and 25 mg dose. Three and 6 mg had no effect on blood pressure or metabolic parameters.     

A remote hypertension management program clinical algorithm

IntroductionHypertension is the leading risk factor for death, affecting over one billion people worldwide, yet control rates are poor and stagnant. We developed a remote hypertension management program that leverages digitally transmitted home blood pressure (BP) measurements, algorithmic care pathways, and patient–navigator communications to aid patients in achieving guideline‐directed BP goals.MethodsPatients with uncontrolled hypertension are identified through provider referrals and electronic health record screening aided by population health managers within the Mass General Brigham (MGB) health system. Non‐licensed patient navigators supervised by pharmacists, nurse practitioners, and physicians engage and educate patients. Patients receive cellular or Bluetooth‐enabled BP devices with which they monitor and transmit scheduled home BP readings. Evidence‐based medication changes are made according to a custom hypertension algorithm approved within a collaborative drug therapy management (CDTM) agreement with MGB and implemented by pharmacists.Using patient‐specific characteristics, we developed different pathways to optimize medication regimens. The renin–angiotensin–aldosterone system‐blocker pathway prescribed ARBs/ACE inhibitors first for patients with diabetes, impaired renal function, and microalbuminuria; the standard pathway started patients on calcium channel blockers. Regimens were escalated frequently, adding thiazide‐type diuretics, and including beta blockers and mineralocorticoid receptor antagonists if needed.DiscussionWe have developed an algorithmic approach for the remote management of hypertension with demonstrated success. A focus on algorithmic decision‐making streamlines tasks and responsibilities, easing the potential for scalability of this model. As the backbone of our remote management program, this clinical algorithm can improve BP control and innovate the management of hypertension in large populations.