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

Diazoxide is a potent antihypertensive agent due to its peripheral vasodilator action. For this reason it is used in the management of hypertensive crises in pregnancy. To assess the effects of an intravenous bolus injection of diazoxide on maternal and fetal hemodynamics an experimental study was performed in 11 chronically instrumented pregnant sheep. In six ewes hypertension was induced by surgical removal of one kidney and reduction of arterial blood flow to the remaining kidney (one-kidney renovascular hypertension). The other five ewes remained normotensive. In a second operation, one week after the first one, the animals were equipped with electromagnetic flow transducers and catheters for monitoring of blood flow in a renal, a uterine, and an umbilical artery and for measurement of maternal and fetal arterial blood pressures, and blood sampling. Maternal heart rate was derived from the arterial pressure curve, fetal heart rate from a fetal ECG. Experiments were begun on the third day after the second operation. In each experiment a bolus of 300 mg of diazoxide was administered intravenously, with or without rapid simultaneous infusion of 500 ml of a plasma expander. A total of 17 experiments were performed in the one-kidney hypertensive ewes (Group H), nine with and eight without plasma expander. In the five normotensive animals (Group NH) 10 experiments were done, four with and six without plasma expansion. During the control periods maternal arterial pressure was approximately 30 mm Hg higher in Group H than in Group NH. In Group H also maternal heart rate, and renal and uterine vascular resistances were significantly elevated. All fetal variables were equal in both groups. Administration of diazoxide without simultaneous plasma expansion resulted in both groups in a significant fall in maternal arterial pressure, a rise in maternal heart rate, and a fall in uterine and renal blood flows with a rise in vascular resistance. Fetal arterial pressure and umbilical blood flow showed no significant changes, but fetal heart rate showed a transient fall together with a drop in fetal pO2 and pH, although acidosis did not occur. When diazoxide was combined with a plasma expander maternal blood pressure did not change significantly in Group NH, but fell in Group H. Maternal heart rate rose significantly in both groups. The decrease in uterine and renal blood flows which occurred when diazoxide was given without plasma expansion was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of diazoxide on maternal and fetal circulations in normotensive and hypertensive pregnant sheep. 647 Sep 17

Intravenous diazoxide was given to 8 patients with severe pregnancy-associated hypertension (diastolic pressure greater than or equal to 110) in the antepartum period. Maternal hypertension was rapidly controlled in all patients; the diastolic blood pressure fell to less than or equal to 100 in all patients and to less than or equal to 85 in 7. Diazoxide had no significant effect on the basal fetal heart rate (FHR) or on the latency period or amplitude of late decelerations in the 3 patients with abnormal (positive) stress cardiotocographs (SCTG) and abnormal (unreactive) non-stress cardiotocographs (NSCTG). In the 5 patients with reactive NSCTGs, diazoxide had no significant effect on the basal FHR or on the frequency of fetal movement-induced FHR accelerations. Thus, diazoxide did not adversely affect fetal well-being in these patients with severe pregnancy-associated hypertension as assessed by cardiotocography.
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PMID:Effect of diazoxide on the antepartum cardiotocograph in severe pregnancy-associated hypertension. 694 17

Drugs used to treat hypertensive emergencies should have the characteristics of rapid action, short duration, high potency, reversibility, a low toxic/therapeutic ratio, no association tachyphylaxis, and a specific action on the cardiovascular system. Of the three mentioned only SNP fulfills all of the requirements. SNP is used, with few exceptions, to treat hypertensive crisis. Trimethaphan camsylate is useful in preventing hemorrhage secondary to a dissecting aneurysm; the other drugs may worsen the tear. Diazoxide is good when no prolonged monitoring is available, since the drug is administered as a bolus rather than an infusion. Side effects, contraindications, and drug interactions are important points to remember during administration of these medications. Care is directed toward limiting or avoiding side effects by titrating the drug and by close observation of the patient. Concurrent maintenance therapy must be initiated to prevent a recurrence of hypertension upon discontinuance of the acute drug protocol.
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PMID:Intravenous drugs used in treating hypertensive emergencies. 702 3

Diazoxide, as usually given in a single bolus, may cause precipitous falls in blood pressure (BP) with resultant tissue hypoperfusion. To examine the efficacy and safety of slow infusion, we treated 18 patients with mean initial BP of 220/143 mm Hg by two regimens: group A (nine patients) received 15 mg/minute; group B (nine patients) received 30 mg/minute. The goal of therapy, diastolic BP of 100 to 105 mm Hg, was reached in 16 of the 18 with no immediate drug-related side effects. Infusion time was 38.1 minutes in group A and 20.7 minutes in group B. Slow intravenous infusion of diazoxide appears to be safe and effective treatment for severe hypertension and should replace the rapid bolus technique.
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PMID:Efficacy of slow infusion of diazoxide in the treatment of severe hypertension without organ hypoperfusion. 706 73

Sudden and large increase of the blood pressure may be life-threatening, particularly when they are accompanied by encephalopathy, left-ventricular insufficiency or other complications. The crisis of hypertension shall be treated possibly without loss of time and with energy. If there is the possibility for a permanent control of the patient, the infusion by drops of nitroprusside sodium is the therapy of choice. It at once decreases the blood pressure and is free of side-effects. Diazoxide has the advantage compared with nitroprusside sodium that an intravenous injection decreases the blood pressure for several hours. But the rapid and drastic decrease of blood pressure may occasionally be dangerous in patients with coronary insufficiency and cerebral arteriosclerosis. In certain indications also other medicaments, such as reserpine, alpha-methyldopa, phentolamine, saralasin or nifedipine can be applied. The crisis of hypertension is always to be regarded as an emergency situation, since always irreversible lesions may be appear on the different organs as a sequel of the permanent vasoconstriction and ischaemia.
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PMID:[Hypertensive crisis and its treatment]. 721 Jul 50

Effects of diazoxide, a benzothiadiazine derivative, on the blood pressure, excretion of Na+, K+, and Ca2+, and the levels of these electrolytes in serum, kidney, and aorta were studied in rats with deoxycorticosterone acetate (DOCA)-induced hypertension in comparison with rats treated with hydrochlorothiazide. After a lateral nephrectomy, 5 mg kg-1 of DOCA was injected subcutaneously three times a week. Drinking water for the rats injected with DOCA contained 1% NaCl. Systolic blood pressure in the DOCA-induced hypertensive rats became about 170 mmHg, with associated elevation of serum level of Na+ 7 weeks after the treatment, whereas that in the normotensive rats was about 100 mmHg. In the DOCA-hypertensive rats, urinary output, and renal excretion of Na+ and Ca2+ increased, and aortic tissue level of Ca2+ decreased as compared with those in the normotensive rats. After 7 weeks of the treatment, diazoxide (10 mg kg-1) or hydrochlorothiazide (10 mg kg-1) was injected intravenously. Diazoxide decreased the blood pressure in both DOCA-hypertensive and normotensive rats, whereas hydrochlorothiazide decreased it only in the DOCA-hypertensive rats. Diazoxide recovered the tissue aortic Ca2+ level that had been decreased by hypertension to that in the normotensive rats. Diazoxide may improve Ca2+ perturbation in the vascular smooth muscle due to DOCA-induced hypertension.
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PMID:Effect of diazoxide on serum and tissue electrolyte levels in rats with deoxycorticosterone acetate-induced hypertension. 807 25

Treatment of hypertension has reduced the incidence of stroke, heart failure and renal failure. However, the incidence of coronary heart disease is not reduced to the same degree. Many of the drugs advocated as first-line drugs in the step-wise therapy have been shown to cause carbohydrate intolerance and it is an independent risk factor in the development of coronary heart disease. It is thus important to identify the antihypertensive drugs that may cause deterioration in glucose tolerance. Cicletanine, the first derivative of the furopyridines, is a new class of antihypertensive agents. It acts directly on vascular endothelium cells by increasing prostacyclin synthesis. It also decreases intracytosolic calcium levels in smooth muscles. The purpose of this study is to evaluate the effects of Cicletanine on insulin release in rat isolated pancreas by the perfusion technique adapted from Loubatieres and co-workers (1972). Doses used were based on therapeutic peak plasma concentration. Diazoxide was used as a positive control ie a known insulin suppressant. Cicletanine at 1/10 and equivalent therapeutic concentrations (0.5 microgram/mL and 5.0 micrograms/mL) did not suppress insulin release. However, at concentration exceeding 10X its therapeutic levels (50 micrograms/mL) it begins to suppress insulin release. In conclusion, Cicletanine did not inhibit insulin release at concentrations within the therapeutic range.
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PMID:The effects of Cicletanine, a new antihypertensive agent on insulin release in rat isolated pancreas by the perfusion technique. 894 29

Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.
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PMID:Clinical pharmacokinetics of vasodilators. Part I. 964 8

Diazoxide is a benzothiadiazine used in oral and intravenous preparations to treat hypertension and hypoglycaemia, but its effect on embryonic development has not been well studied. Previous in vivo work has suggested placental transfer and teratogenicity of diazoxide in humans and laboratory animals, but this study represents the first in vitro investigation of the effect of diazoxide on the embryo. The in vitro method of whole-embryo culture was used to expose mouse embryos to specific levels of diazoxide (0-200 mug/ml) during organogenesis at well-defined (4-6 and 20-25 somite) stages of development. In addition, the combined effect of diazoxide [ATP-sensitive K(+) (K(ATP)) channel opener] and the sulfonylurea oral hypoglycaemic agent chlorpropamide (K(ATP) channel blocker), was evaluated in vitro in embryos with 4-6 somites. Diazoxide produced malformations and growth retardation in mouse embryos exposed to 100 mug/ml or more for 24 hr in vitro at both stages of organogenesis. In addition, a subteratogenic concentration of diazoxide (25 mug/ml) reduced the embryopathic effects of chlorpropamide (130 mug/ml) in embryos with 4-6 somites. A potential mechanism for these effects involves K(ATP) channels.
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PMID:Embryopathic effects of diazoxide and the reduction of sulfonylurea-induced dysmorphogenesis in vitro. 2069 80

Diazoxide is a non-diuretic benzothiadiazine derivative, one of a group of substances introduced into clinical practice in the 1950s for the treatment of hypertension. Fajans reported the use of diazoxide for the treatment of insulinoma in 1979. Although patients with hyperinsulinemic hypoglycemia worldwide have been treated with diazoxide for more than 30 years, there are no recent reports about the adverse effects of this drug in Asian patients, including Japanese patients. Herein, we report the results of our retrospective clinical record review of 6 Japanese patients (3 females and 3 males, ranging in age from 58 to 91 years) with hyperinsulinemic hypoglycemia and inoperable insulinoma treated with diazoxide. Diazoxide improved control of hypoglycemic symptoms and maintained normoglycemia in 5 of the 6 patients, and was ineffective in one patient. Surprisingly, although all 6 patients received diazoxide according to the treatment strategy recommended in Western patients, 5 of the 6 patients developed edema and two developed congestive heart failure. Thus, when starting treatment with diazoxide in Japanese patients, the symptoms and signs of fluid retention should be evaluated carefully. Also, appropriate protocols for treatment with diazoxide should be evaluated by means of clinical trials in Japanese patients with hyperinsulinemic hypoglycemia.
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PMID:Safety and tolerability of diazoxide in Japanese patients with hyperinsulinemic hypoglycemia. 2659 36


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