Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) The initial treatment of obesity must include an attempt to modify previous eating pattern and may involve group therapy or behavioral modification. Drug treatment is not indicated unless this dietary approach is shown to be ineffective. (2) Since anti-obesity drugs do not help to establish a new and permanent eating habit, they should never be prescribed except as part of an overall management plan. (3) The potential for abuse with amphetamine and phenmetrazine is such that their use cannot be justified as anorectic agents. (4) Phenmetrazine, diethylpropion, mazindol and fenfluramine will all produce an additional mean weight loss of approximately 0.2 kg per week. They are contraindicated if there is a history of drug misuse, drug dependence or psychiatric illness. They should always be prescribed with caution. With the exception of fenfluramine, they are best given intermittently on the grounds of efficacy, safety and cost benefit. (5) The individual response to drug therapy is extremely variable and may reflect differences in drug pharmacokinetics, metabolic adaptation or, less frequently, drug tolerance. (6) Following drug withdrawal, weight regain is the rule. It follows that therapy can most easily be justified if there is a short term need for weight loss, e.g. prior to elective surgery. (7) The safety and efficacy of long term drug therapy has yet to be established. It may prove justifiable in patients most at risk from obesity or from obesity associated disorders such as diabetes and hypertension. However, at present the only established indication for prolonged administration of the currently available drugs is the use of metformin in insulin independent diabetics. (8) The indications for the pharmacological treatment of obesity remain poorly defined. A number of new approaches are being evaluated, and the future may lie in the development of drugs which enhance thermogenesis or primarily act upon the gastrointestinal tract.
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PMID:Drug treatment and obesity. 676 69

Captopril was used in primary and long-term treatment of 40 treatment-resistant hypertensive patients. Of these, 21 had renovascular hypertension, seven unilateral and fourteen bilateral, and 19 had essential hypertension, 10 with high-renin and 9 with normal-renin profiles. All patients were off treatment when started on captopril therapy and were treated for at least 12 months, on the average for more than 2 years. The strategy of systematic drug withdrawal used to find the lowest effective dose of captopril led to average doses of 150 to 300 mg/day. A diuretic agent was added in 17 of the 40 patients when diastolic pressure remained greater than 105 mm Hg and a beta-adrenergic blocking agent was added for tachycardia or additional pressure control in 16 patients. Captopril alone was effective in 14 of the 40 patients. In all groups, mean supine and standing blood pressure levels were maintained at less than 140/90 mm Hg without evidence of decreased effectiveness over time. Control and treatment systolic pressures were higher in patients older than 50 years. For patients of all ages, systolic but not diastolic pressure during captopril treatment was higher in the supine position than standing. Plasma renin activity remained significantly elevated over time and aldosterone excretion usually decreased despite concurrent diuretic therapy. Captopril alone or in combination with a diuretic or beta-adrenergic blocking agent is effective in long-term treatment of drug-resistant renovascular and essential hypertension.
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PMID:Long-term efficacy of captopril in renovascular and essential hypertension. 680 61

Bilateral optic atrophy developed in a 15-year-old patient receiving concomitant neuraxis radiation therapy and weekly vincristine sulfate for medulloblastoma. Other neurologic manifestations that have been associated with vincristine therapy, including inappropriate secretion of antidiuretic hormone, hypertension, confusion, and a severe peripheral neuropathy, were also observed. Neither increased intracranial pressure nor active tumor was identified. Recovery of visual function followed discontinuation of vincristine. Other neurotoxicities also reversed with drug withdrawal. Visual loss occurring in a patient receiving vincristine should alert the physician to the possibility that the process is drug related. This complication may be more likely in patients receiving concomitant or previous cranial radiation therapy. Other central neurotoxicities of vincristine may also be accentuated by neuraxis radiation. It is recommended that vincristine be discontinued in this situation if an aggressive search for a structural anatomic lesion in the optic mechanism is unrevealing, as the prognosis for recovery of visual function appears excellent.
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PMID:Optic atrophy induced by vincristine. 709 98

The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37 +/- 0.09 micrograms/ml-1 at 1.92 +/- 1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78 +/- 0.77 h and 10.78 +/- 7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50--200 mg t.i.d. During in-patient administration of 600--900 mg T daily (n = 6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n = 4) was associated with a significant fall in mean systolic but not diastolic by (lying -15/+1 mm Hg. standing -25/-8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean +/- SD) significantly from 55 +/- 5/min to 66 +/- 8/min following 900--1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600--900 mg daily eventually necessitated drug withdrawal. In its present form T is not recommended for the treatment of hypertension.
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PMID:A clinical and pharmacokinetic evaluation of tolmesoxide in hypertensive patients. 720 70

Among the physicochemical, pharmacokinetic and pharmacodynamic properties that differentiate trandolapril from other angiotensin converting enzyme (ACE) inhibitors, the most clinically relevant ones are those that contribute to the long duration of action of the drug. The long elimination half-life of trandolapril and its strong lipophilicity, high ACE inhibitor potency and high affinity for the ACE cause the drug to have a long biological half-life. The long duration of action of trandolapril may be demonstrated experimentally; near total ACE inhibition is observed 24 hours after single dose administration and there is significant ACE inhibition 72 hours following drug withdrawal after long term therapy. We have analysed the duration of blood pressure lowering during long term therapy with commercially available ACE inhibitors in published studies using ambulatory blood pressure monitoring. On the basis of results from 19 studies undertaken in patients with mild to moderate hypertension, it was possible to reconstruct the curve of the magnitude of blood pressure changes against time. Mean trough: peak ratio calculations showed that once-daily administration produced ratios higher than 50% with enalapril (40 to 80%), lisinopril (40 to 70%) and trandolapril (50 to 100%). Other ACE inhibitors had trough: peak ratios lower than 50%. Despite many methodological limitations, this literature analysis demonstrates that trandolapril has a blood pressure-lowering effect for the full 24-hour period. Studies in which a dose is occasionally omitted show that the blood pressure-lowering effect of trandolapril may last beyond 24 hours.
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PMID:Trandolapril. How does it differ from other angiotensin converting enzyme inhibitors? 751 72

A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.
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PMID:Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow. 753 22

In 26 patients with mild-to-moderate hypertension, 80.8% of whom had a history of concomitant diseases, the effect of moxonidine (0.2 mg b.i.d.) on the 24-h ambulatory blood pressure profile (ABPM) was compared with captopril (25 mg b.i.d.) in a double-blind, parallel-group study. After 4 weeks of treatment with placebo, ABPM was performed and the patients were treated with moxonidine (n = 14) or captopril (n = 12) for a further 4 weeks. ABPM was then repeated. Both moxonidine and captopril reduced systolic and diastolic blood pressure sufficiently and to the same extent. Mean 24-h pulse rate and standard laboratory parameters were not changed by active treatment. After drug withdrawal for 5 days, sitting blood pressure did not differ from baseline values in both groups. Serious adverse events did not occur, the most frequent complaints were nausea (2 of 14 patients receiving moxonidine) and dizziness (3 of 12 patients receiving captopril). We concluded that the blood pressure-lowering effects of moxonidine (0.2 mg b.i.d.) and captopril (25 mg b.i.d.) are comparable in patients with mild-to-moderate hypertension.
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PMID:Twenty-four-hour blood pressure profiles in patients with mild-to-moderate hypertension: moxonidine versus captopril. 753 24

A sympathetic overactivity plays a major role in the pathogenesis of cardiovascular diseases in Westernized affluent societies. Of importance is an increased caloric intake and psychosocial stress which are associated with a raised central sympathetic outflow and unfavourable changes in metabolic parameters. Normalization of central sympathetic outflow could thus be a major therapeutic target. The newly developed antihypertensive drugs moxonidine and rilmenidine reduce the excitatory activity of neurons of the rostral ventrolateral medulla (RVLM) via binding to imidazoline receptors. Using radio telemetry, it is shown that, in contrast to the first generation centrally acting drug clonidine, moxonidine did not result in rebound of blood pressure after drug withdrawal in rats with spontaneous hypertension. In accordance, moxonidine is characterized by a low affinity for alpha-adrenoceptors and exhibits few side-effects. It is proposed that normalization of central sympathetic outflow represents a causal approach for improving crucial features of the metabolic syndrome.
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PMID:Excess catecholamines and the metabolic syndrome: should central imidazoline receptors be a therapeutic target? 760 78

Studies of antihypertensive drug withdrawal suggest that at least 20% of selected older patients with hypertension can remain normotensive without drug treatment for periods of up to 5 years. Success of drug withdrawal is greater in those patients controlled on low dose monotherapy who have low on-treatment blood pressure (BP), are not overweight and who have no ECG evidence of left ventricular hypertrophy. Compliance with lifestyle advice may increase the chance of successful drug withdrawal. Unfortunately, many older hypertensive patients have poorly controlled BP despite treatment with antihypertensive drugs, and are overweight. These factors limit opportunities for drug withdrawal although they may not be so much of a problem in the very elderly. Patient who could be considered for a trial of antihypertensive drug withdrawal are those unhappy with such therapy who also: (a) have well controlled BP on monotherapy with no significant target organ damage, (b) have 'white-coat' hypertension, or (c) are very elderly (> 80 years). The withdrawal of antihypertensive drugs can improve drug-induced metabolic abnormalities and symptoms, and appears safe providing there is a gradual reduction in drug dosages and close follow-up to detect a return to hypertension.
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PMID:Withdrawal of antihypertensive therapy in the elderly. The issues. 766 63

We studied the long-term effects after withdrawal of enalapril, an angiotensin-converting enzyme inhibitor, on tail systolic pressure and cardiovascular structural properties in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Observations in control rats were from 4 to 35 weeks of age, whereas treated rats received enalapril from 4 to 20 weeks and were studied for a further 15 weeks. We measured blood pressure and the ratio of left ventricle weight to body weight and derived methoxamine log dose-perfusion pressure curves in the isolated hindquarter bed. From the changes in resistance properties we also estimated the changes in structure using a model developed previously. During therapy, blood pressure was depressed to a common value in both strains. After drug withdrawal, by age 35 weeks, previously treated SHR developed only mild hypertension, whereas blood pressure of WKY had recovered to the corresponding control level. At 21 weeks, soon after enalapril was stopped, left ventricular development was depressed in both strains; the depression was slightly greater in SHR, but that of vascular resistance was proportionately similar in each strain. Late cardiovascular development between 21 and 35 weeks was attenuated in the previously treated groups. For the left ventricle, it was similar in each strain, but for the vasculature, late development was relatively smaller in SHR than WKY. In the former, the pattern of development between 21 and 35 weeks was the same as in untreated controls and appeared to be mediated in response to the rise in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Cardiovascular development after enalapril in spontaneously hypertensive and Wistar-Kyoto rats. 772 5


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