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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diuretic monotherapy has been recommended by the fifth report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC-V) as a preferred initial treatment for hypertension. Thiazide diuretics are commonly used to treat hypertension because of their demonstrated efficacy, favorable safety profile, low acquisition cost, and their proven ability to reduce blood pressure-related morbidity and mortality. 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. Blood pressure reductions with low-dose hydrochlorothiazide and chlorthalidone are comparable to that achieved with higher doses (25 and 50 mg/day). Additional blood pressure reductions can be attained with concomitant use of once-daily low-dose hydrochlorothiazide or chlorthalidone with an angiotensin-converting enzyme (ACE) inhibitor, a beta blocker, or a calcium antagonist. Once-daily low-dose hydrochlorothiazide provides clinically meaningful blood pressure lowering while minimizing adverse effects, such as electrolyte disturbances, cholesterol elevations, and increases in serum uric acid levels.
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PMID:Evidence for the efficacy of low-dose diuretic monotherapy. 887 75

The safety and tolerability of antihypertensive therapies are an important clinical concern, because the demonstrated benefits of successful blood pressure-lowering depend on long-term compliance with pharmacologic treatments. Thiazide diuretics and beta blockers have been specifically recommended as preferred initial drug therapy by the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), unless their use is contraindicated by concomitant disease, there is intolerance to these agents, or there is a specific indication for another drug class. These recommendations are a result of the lengthy clinical experience with these drugs and the results of long-term clinical trials that have demonstrated significant reductions in cardiovascular morbidity and mortality. However, data from these same clinical studies have also shown that diuretics (and beta blockers) can cause abnormalities in carbohydrate, electrolyte, and lipid metabolism and also may influence quality of life. The safety of diuretics was evaluated with regard to effects on carbohydrate, electrolyte, and lipid metabolism by seeking references from a MEDLINE search of documents published from 1966 to 1994 based on the search terms "hypertension," "human," and "hydrochlorothiazide" (HCTZ) dosed in a range of 12.5-25 mg daily. 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. During the course of treatment with HCTZ in these studies, serum potassium was reduced and uric acid was increased in a dose-dependent manner. Although low doses of HCTZ elevated serum glucose, cholesterol, and triglycerides, the magnitude of effect was small in most cases and was probably of no clinical significance. Other laboratory parameters were not adversely affected, and subjective reporting of clinical adverse events was generally lower with low-dose HCTZ than with placebo or standard HCTZ dosing. The literature on the effects of low-dose diuretic therapy on quality of life is not large, although the results from the SHEP and TOMHS studies support the concept that diuretics either do not interfere with, or may actually improve, quality of life in hypertensive patients. Low-dose thiazide treatment is a well-tolerated, excellent first-line choice for hypertensive patients, especially older patients. However, diuretics should probably be avoided, whenever possible, in patients with preexisting diabetes, gout, and in men with erectile dysfunction.
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PMID:Tolerability, safety, and quality of life and hypertensive therapy: the case for low-dose diuretics. 887 78

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.
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PMID:[Guidelines on treatment of hypertension in the elderly, 1995--a tentative plan for comprehensive research projects on aging and health-- Members of the Research Group for "Guidelines on Treatment of Hypertension in the Elderly", Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare of Japan]. 905 55

Diuretics have changed the approach to many disease and have turned once fatal conditions into tolerable ones. Treatment of salt and water overload and edema can be quite satisfying for the clinician as long as the patient is closely watched for side effects. Thiazide diuretics have their greatest use in hypertension, loop diuretics in edema and congestive heart failure, CA inhibitors in glaucoma and altitude sickness, potassium-sparing diuretics in hypokalemia induced by other diuretics and ascites, and osmotic diuretics in acute renal failure and dialysis. They are among the most widely prescribed medications in the world today and rightly have a prominent place in the armamentarium against disease.
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PMID:Edema and principles of diuretic use. 916 52

Thiazide diuretics have antihypertensive efficacy equivalent to that of the other major classes of antihypertensive drug, and are at least as well tolerated as judged by discontinuation rates and measures of quality of life. They are effective when given once daily, require no dose titration, have few contraindications, and have additive effects when combined with drugs of other classes. The dose-response relation for blood pressure is flat, whereas the subjective and biochemical side-effects are dose-dependent. They should be prescribed only at low dosage. Treatment regimens based on low-dose thiazide prevent stroke, coronary events, heart failure and renal failure in hypertension, and have proven safety. Thiazides are inexpensive. Low-dose thiazides should be preferred for routine first-line treatment of hypertension unless they are contraindicated or there is a compelling indication for an alternative class of drug.
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PMID:Thiazide diuretics in hypertension. 1042 3

Recent studies using molecular biological methods have enabled us to identify the genetic abnormality in renal electrolyte metabolism. In renal tubules, diuretic sensitive Na transporter systems are present, and key molecules have been cloned. Thiazide-sensitive Na-Cl contransporter (TSC) is one of the molecules localized in the distal convoluted tubule, whose genetic abnormality causes Gitelman's syndrome (a variant of Bartter's syndrome characterized by dehydration, hypokalemic metabolic alkalosis, secondary aldosteronism lacking hypertension, hypomagnesemia, and hypocalciuria). We identified a mutation in TSC (Leu to Pro change at 623 amino acid position, L623P) in familial Gitelman's syndrome, and we confirmed the loss of TSC function by this mutation in a functional expression system using mammalian cells. This L623P mutation has been found in other patients with Gitelman's syndrome living in the northern part of Japan.
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PMID:[Renal sodium transport abnormality: Gitelman's syndrome and renal sodium transporter]. 1063 22

The pharmacotherapeutic use of lithium in the elderly as acute and maintenance therapy in bipolar disorder and augmentation therapy for major depression is well documented. Differences in the response to lithium are explained, in part, by the effect of age-related physiological changes, comorbid conditions, and concurrent medications on the pharmacokinetics of lithium in the elderly. The pharmacokinetic profile of lithium has been studied for many years, primarily in younger adult populations. Lithium pharmacokinetics may be influenced by a number of factors including age. It was first noted several years ago that elderly individuals required lower doses of lithium to achieve serum concentrations similar to those observed in younger adults. This is due to the combination of a reduced volume of distribution and reduced renal clearance. The composition of the human body changes with aging producing an increase in body fat, a decrease in fat-free mass and a decrease in total body water. Lithium clearance decreases as the glomerular filtration rate decreases with increasing age. The effects of other medical conditions in the elderly on the pharmacokinetics of lithium are less well delineated. Reduced lithium clearance is expected in patients with hypertension, congestive heart failure or renal dysfunction. Larger lithium maintenance doses are required in obese compared with non-obese patients. The most clinically significant pharmacokinetic drug interactions associated with lithium involve drugs which are commonly used in the elderly. Thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs can increase serum lithium concentrations. The tolerability of lithium is lower in the elderly. Neurotoxicity clearly occurs in the elderly at concentrations considered 'therapeutic' in general adult populations. There are no placebo-controlled randomised trials of lithium in old age and recommendations for clinical use are based on extrapolations from pharmacokinetic studies, anecdotal reports from mixed age populations and clinical experience in old age psychiatry. Serum concentrations of lithium need to be markedly reduced in the elderly population and particularly so in the very old and frail elderly.
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PMID:Differential pharmacokinetics of lithium in elderly patients. 1080 57

The novel antihypertensive drugs which have been discovered and developed in the latter half of the 20th century were investigated. Newly discovered or improved drugs are approved by the Ministry of Health and Welfare in Japan, and after then they become available for clinical use. We can follow the progress and trends of various new antihypertensive drugs by recording their years of approval. The four primary useful drugs for the treatment of hypertension were developed were introduced as listed in the following: 1. Antihypertensive diuretics: Thiazide and dihydrothiazide were first approved in 1958, and various related drugs including aldosterone antagonists and loop diuretics followed. 2. beta-Adrenergic-blocking drugs: Propranolol was approved in 1966 for heart diseases and for hypertension in 1970. Thereafter many related drugs were developed. 3. Calcium channel-blocking drugs: Nifedipine was approved, for heart disease in 1974 and for hypertension in 1981, and then many related drugs appeared. 4. Angiotensin-converting enzyme inhibitors: Captopril was approved in 1982 and thereafter various related drugs followed. The four categories of these drugs were selected as first choice drugs for the treatment of hypertension in 1988. The development of these excellent useful drugs affected the mortality rates of cerebrovascular diseases (e.g., apoplexy). The mortality curve reaches plateaued in 1963, peaked in 1965, and then declined rapidly. Antihypertensive diuretic drugs stop the rise of mortality, and beta-blocking drugs, Ca-antagonists and ACE-inhibitors promote rapid downward tendency.
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PMID:[Fifty years history of new drugs in Japan: the developments and trends of antihypertensive drugs]. 1164 Feb 8

Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects.
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PMID:Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. 1210 33

Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors are all superior to placebo for the primary prevention of coronary events in patients with hypertension. Recent studies have shown that ACE inhibitors are better than other antihypertensive agents in lowering overall cardiovascular morbidity and mortality, especially stroke. Blood pressure should be aggressively lowered (to < 140/90 mm Hg), especially in diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering the diastolic blood pressure below 65 mm Hg in patients with significant occlusive coronary artery disease. Hypertension in patients with stable angina should be treated with a b-blocker (alternatively a calcium channel blocker) together with an ACE inhibitor. Patients with hypertension and acute coronary syndrome (unstable angina or myocardial infarction) should be treated with a b-blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added for blood pressure control. Calcium channel blockers should be avoided if there is significant left ventricular dysfunction.
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PMID:Managing the hypertensive patient with ischemic heart disease. 1221 52


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