Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period. In the whole group mean arterial blood pressure fell to levels of less than or equal to 107 mm Hg or declined by more than 15 mm Hg in 78% of the patients after twelve weeks of treatment. Sixty-nine percent of patients receiving hydrochlorothiazide alone developed serum potassium levels lower than 3.5 mEq/L; serum potassium levels were above 5.5 mEq/L in 2 patients (5.5%) receiving spironolactone 400 mg/day. Uric acid levels rose in all patients, more in those on hydrochlorothiazide, but clinical gout did not develop in any subject. Hydrochlorothiazide, spironolactone, and the combination of the two are effective antihypertensives. Spironolactone in doses of 200 and 400 mg/day was associated with side effects but did not induce a greater antihypertensive effect than doses of 100 mg/day. Our data suggest that when hydrochlorothiazide is associated with potassium loss, when gout or elevated uric acid levels are of concern, or when carbohydrate tolerance is abnormal, supplementation or replacement with spironolactone (up to 100 mg/day) may be useful in controlling blood pressure while reducing side effects.
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PMID:Hydrochlorothiazide and spironolactone in hypertension. 36 34

The safety and efficacy of tienilic acid have been evaluated in studies of patients with mild to moderate essential hypertension, salt and water retention states and hyperuricaemia associated with gout. During the course of these studies 675 patients were treated with tienilic acid, 310 were treated with hydrochlorothiazide, 43 were treated with probenecid and 34 were treated with placebo. Overall, adverse reactions characterized as probably drug-related or questinably drug-related were reported in 28% of patients treated with tienilic acid, 24% treated with hydrochlorothiazide, 25% of patients treated with probenecid and 33% treated with placebo. The side effects encountered were mild in severity, reversible and represented extensions of the pharmacological activity of tienilic acid, hydrochlorothiazide and probenecid. These initial studies demonstrate that tienilic acid is safe and effective in the treatment of mild to moderate essential hypertension, salt and water retention states, including oedema associated with congestive cardiac failure or mild to moderate renal dysfunction, and in the management of elevated serum uric acid levels associated with gout.
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PMID:Safety of tienilic acid. 38 98

Weight reduction is almost always successful in cases of essential hypertension if and when the weight loss is accompanied by a drastic sodium reduction. (2) Weight normalization is of remarkable help in complete reversal of abnormal glucose tolerance, decrease in insulin requirement in manifest diabetes mellitus, and - in many patients with mild diabetes - discontinuation of oral hypoglycemic agents. (3) Weight loss will occasionally relieve gout patients of their symptoms. The majority of hyperuricemic patients will benefit with a lowering of serum uric acid levels. (4) An unresolved issue is the influence of weight reduction on the cholesterol metabolism - short- and long-term results are by no means predictable. Whereas the triglycerides in obese patients almost always return to lower serum concentrations, and with them the hyperlipoproteinemias of type IIB, III and IV, the type IIA is only rarely seen in association with obesity. Therefore, information on this lipid abnormality is very limited regarding the effect of weight loss.
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PMID:The workinghman's diet. II. Effect of weight reduction in obese patients with hypertension, diabetes, hyperuricemia and hyperlipidemia. 63 8

Felodipine is a dihydropyridine calcium antagonist which may be administered once daily in an extended release (ER) formulation. As monotherapy in older patients with mild to moderate essential hypertension, felodipine ER once daily provides effective control of blood pressure (BP). The drug has also been effective, either as monotherapy or in combination with other antihypertensive medications, in comparisons with other antihypertensive agents, and does not adversely affect lipid profiles or, in patients with diabetes mellitus, glycaemic control. Results in patients with angina pectoris and congestive heart failure indicate a potential role for felodipine ER in these indications and data also suggest the drug reduces left ventricular hypertrophy. In addition, felodipine ER appears suitable for use in patients with concomitant respiratory disease, renal or hepatic dysfunction, cerebrovascular or peripheral ischaemic disease, or gout, making it particularly useful in the elderly who often have more than one significant clinical condition. Felodipine ER has generally been well tolerated by older patients in clinical trials, although further confirmation in the long term is desirable. Thus, felodipine ER effectively lowers BP in older patients with essential hypertension with the added convenience of once daily administration. It may be used as monotherapy or in combination with other antihypertensive agents and is a practical advance in the treatment of hypertension in the elderly.
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PMID:Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in older patients. 139 20

Thiazide diuretics are efficacious, either as monotherapy or in combination with other antihypertensive drugs. They reduce blood pressure in a high percentage of hypertensive patients with minimal subjective side effects. There is increasing evidence that the use of diuretics, singly or in combination, will reduce morbidity and mortality associated with essential hypertension in both young and elderly subjects. Although diuretics may induce some changes in the plasma lipid profile, serum uric acid concentration and glucose metabolism, there is little evidence that these changes are of clinical significance. The increase in serum cholesterol concentration has rarely persisted in any trial beyond the first year of treatment. The incidence of diabetes mellitus in diuretic treated subjects is only about 1%, even when large doses are used. Gout may be precipitated in susceptible subjects, but is uncommon. For these reasons, diuretics should remain a preferred first-step drug of choice in the management of hypertension.
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PMID:Diuretics and cardiovascular risk factors. 148 10

Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents.
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PMID:The cardiotoxicity of thiazide diuretics: review of the evidence. 221 84

The drug treatment of mild hypertension has been shown to afford protection against fatal and nonfatal strokes, congestive heart failure, progression to more severe levels of hypertension, and all-cause mortality, but not against the complications of coronary artery disease. The lack of benefit against coronary artery disease may result from failure to reduce other risk factors or because the drugs employed increased coronary risk. It can be taken as axiomatic that effective preventive antihypertensive therapy is more likely with drugs with mechanisms and sites of action that are focused on the underlying pathophysiology than with drugs that lower blood pressure by means unrelated to the hypertensive process. Adrenergic predominance plays a major role in the initiation and maintenance of essential hypertension and, consequently, the alpha-adrenergic receptor inhibitors were among the first substances to receive serious consideration as antihypertensive agents. However, since these drugs are nonselective, feedback control of transmitter norepinephrine was lost and, consequently, the clinical expectations of the early alpha-adrenergic receptor inhibitors in the treatment of high blood pressure were not fulfilled. The discovery of selective postjunctional alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, which preserve feedback control of transmitter norepinephrine release, was the crucially important step in the development of specific drugs to combat the hyperactivity of adrenergic vasoconstrictor nerves in hypertension. These drugs have been shown to normalize hemodynamics in hypertensive patients. They lower blood pressure through a reduction in peripheral resistance at rest and during exercise, independent of changes in heart rate and blood pressure, with minimal reflex activation or tolerance development. Alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, represent an attractive choice for initial therapy in all grades of hypertension and are especially appropriate in hypertensive patients with congestive heart failure, asthma and chronic obstructive airways disease, renal impairment, diabetes mellitus, hyperlipidemia, benign prostatic hyperplasia, or gout, and in those involved in vigorous work, sports, or exercise. There are no known contraindications to these drugs, except in patients who are sensitive to quinazolines.
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PMID:Pharmacologic basis for the use of doxazosin in the treatment of essential hypertension. 256 23

This paper presents epidemiological data on the prevalence of 26 common (i.e., having a lifetime prevalence of more than 1 per 10(4) individuals in the population) multifactorial diseases in Hungary and estimates of detriment associated with them. The detriment is expressed using 3 indicators, namely years of lost life (LL), potentially impaired life (PIL) and actually impaired life (AIL). The total prevalence of these diseases in Hungary has been estimated to be about 6500 per 10(4) individuals in the population. This estimate is in agreement with published data for other parts of the world. On the basis of clinical severity, these diseases have been split into 3 groups, namely (1) very severe (schizophrenia, multiple sclerosis, epilepsy, acute myocardial infarction and related conditions, and systemic lupus erythematosus); (2) moderately severe and/or episodal or seasonal (15 entities including Graves' disease, diabetes mellitus, gout, affective psychoses, essential hypertension, peptic ulcers, asthma, etc.); and (3) less severe than those in the first 2 groups (varicose veins, allergic rhinitis, atopic dermatitis, Scheuermann disease and adolescent idiopathic scoliosis). The essential clinical and genetic aspects of these diseases are briefly discussed. With the exception of epilepsy, none of the diseases included in our list causes mortality between ages 0 and 19. However, they are among the leading causes of death between ages 20 and 69 and thereafter. A sizeable proportion of those with essential hypertension, diabetes mellitus, rheumatoid arthritis, etc. survive to 70 years and beyond, as do those with gout, glaucoma, allergic rhinitis, psoriasis, etc. Overall, about 16% of all deaths that occur in Hungary every year (all age groups) can be attributed to these diseases. The mean number of years of PIL covers a wide range (about 20-40, 12-70 and 40-60 for groups 1, 2 and 3, respectively), the overall mean being about 24 years. However, the nature and degree of impairment and the impact on the life quality of those afflicted differ for the different diseases. Likewise, the mean number of years of AIL (for which the interval between the mean age at premature retirement and mean age at death was used as a rough index) also spans a wide range from 16 to 45, and the overall mean is about 20 years. At the population level, the diseases considered in this paper cause about 2700 years of LL, 96,000 years of PIL and about 5800 years of AIL per 10(4) individuals in the population. Relative to Mendelian diseases as a whole, these multifactorial diseases are associated with much greater detriment (LL: 1.4 X; PIL: 30 X and AIL: 3.9 X).
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PMID:The load of genetic and partially genetic diseases in man. II. Some selected common multifactorial diseases: estimates of population prevalence and of detriment in terms of years of lost and impaired life. 305 77

Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.
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PMID:[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension]. 306 60

Hyperuricaemia carries with it a high risk of tophi development affecting connective tissue in kidney, skin and joints, its overt clinical expression being gout. Diuretics, which are invariably prescribed in congestive heart failure and widely used for the treatment of essential hypertension, may cause hyperuricaemia and predispose to gout by inducing renal retention of urate. The angiotensin I converting enzyme inhibitors captopril and enalapril have been found to augment renal urate excretion both in normal volunteers and in hypertensive patients. Current evidence appears to indicate that the uricosuric effect of captopril and enalapril could be due to the rises in renin and angiotensin I these drugs elicit by angiotensin I converting enzyme inhibition, and/or to pharmacological actions not related, at least directly, to the renin-angiotensin-aldosterone system. Serum urate levels have been significantly reduced by monotherapy with captopril in hypertensive patients suffering from hyperuricaemia. Diuretic-induced hyperuricaemia in hypertensive patients can be prevented or counteracted by the administration of captopril and enalapril. Available clinical data support the argument that captopril and enalapril should be used as first choice drugs for the treatment of hyperuricaemic hypertensive patients. When diuretic-induced hyperuricaemia develops in patients suffering from congestive heart failure, captopril or enalapril should be added to the therapeutic regime in doses capable of countering the shift in plasma urate concentration, provided the clinical condition of the patients permits such additional pharmacological treatment. Therapy with captopril and enalapril should preferably be instituted in a gradual manner, especially in patients with hyperuricaemia, in order to prevent the precipitation of urate in the kidney and in the urinary tract.
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PMID:Angiotensin I converting enzyme inhibitors and the renal excretion of urate. 315 8


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