Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A novel formulation of nicardipine (25% standard, 75% sustained release--SR) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled comparison with standard nicardipine (STD), using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. At 2 h after dosing (peak effect) both STD nicardipine (30 mg three times daily) and SR nicardipine (60 mg twice daily) for 28 days produced a highly significant reduction in sitting and standing blood pressure. The mean sitting blood pressure was reduced by 20/16 mm Hg (STD) and by 25/18 mm Hg (SR) compared with placebo. 3. Predose (8-11 h after last dose of STD, 12-15 h after last dose of SR) the reductions in sitting blood pressure relative to placebo were 11/6 mm Hg (STD) and 14/7 mm Hg (SR). 4. Home recordings confirmed the hypotensive effect of both formulations. Both exhibited a distinct 'peak dose' effect between 1-3 h after dosing. The effect of the SR formulation was sustained throughout the 12 h dosing interval. 5. Of the 60 patients entering the study, one died of unexplained staphylococcal septicaema, two were withdrawn for non drug-related reasons and 14 (32%) were withdrawn because of adverse effects on active therapy (headaches, facial flushing, leg oedema, chest pain, dizziness). 6. In the 43 patients who completed the study adverse symptoms were reported more frequently while they were on the two active formulations of nicardipine compared with placebo. Most of these reactions were again of vasodilator origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nicardipine sustained release in hypertension. 195 36

Pheochromocytoma is an unusual but potentially devastating tumor. Although a high index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings. Nonetheless, screening must be broadened to include patients with a lower risk of the disease, such as those with resistant or labile hypertension who are minimally symptomatic. Extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive. Symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma. Certain symptoms are useful: flushing to suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor to suggest that a pheochromocytoma is more likely. Combinations of symptoms can be of value: 2 or more symptoms from the triad of headache, palpitations, and diaphoresis were present in the majority of pheochromocytoma patients, but in a smaller number of non-pheochromocytoma patients. The presence of the entire triad is more specific, but less sensitive. New hypertension, or hypertension associated with unexplained orthostatic hypotension, are suggestive of an underlying pheochromocytoma. Twenty-four-hour urine studies are consistently abnormal in patients with a pheochromocytoma, but are also elevated in a significant proportion of non-pheochromocytoma patients. Values greater then 1.5-2-fold above the upper limit of normal are very suggestive that a pheochromocytoma is present, and warrant a more intensive subsequent evaluation. Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help to confirm or exclude the disease. Patients with a higher clinical likelihood and any elevated urinary testing, or with a lower clinical likelihood and persistently and/or significantly elevated urinary testing, should have imaging studies performed. This combination of clinical screening, 24-hour urinary testing, and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma.
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PMID:A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience. 198 66

Nitrendipine, a new calcium-channel antagonist, was used to treat 25 children (aged 6 months to 17 years) with severe hypertension. Systolic and diastolic blood pressures (mean +/- SEM) fell from 148 +/- 2/99 +/- 2 mm Hg to 128 +/- 4/77 +/- 3 mm Hg after 24 hours and to 121 +/- 2/75 +/- 2 mm Hg after 2 weeks. No further reductions in systolic or diastolic blood pressure were observed after continued therapy. Transient reflex tachycardia occurred during the first week of therapy. Other adverse effects were uncommon and included headaches, flushing, palpitations, and edema. Pharmacokinetic parameters were estimated at steady state after an oral dose of 0.56 +/- 0.04 mg/kg in 13 children. Although absolute oral bioavailability could not be determined, estimates of the area under the plasma concentration versus time curve, the apparent peak serum concentration, and the apparent time at which the peak serum concentration occurred indicated that both the rate of absorption and oral bioavailability are variable. Coadministration of nitrendipine with food decreased the rate of absorption and may have reduced oral bioavailability. A relationship between age and the apparent plasma elimination half-life of nitrendipine was not observed. Nitrendipine, 0.25 to 0.5 mg/kg per dose administered orally every 6 to 12 hours, appeared to be an effective and safe treatment for resistant hypertension in infants and children.
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PMID:Antihypertensive effect and pharmacokinetics of nitrendipine in children. 200 42

There have been major advances in the understanding of the basic pharmacology of drugs acting upon voltage-dependent and receptor-activated calcium channels using patch-clamp techniques. The structure of the L channel is known and the (different) binding sites for various calcium antagonists have been identified using the methods of molecular biology. Although calcium slow-channel antagonists are very widely used in the treatment of hypertension, advances in the clinical pharmacology of angina and, to a lesser extent, cardiac arrhythmias, have not kept up with the basic research in molecular biology. All of the calcium antagonists in current use dilate arteries, and their therapeutic action largely depends on this property. There is evidence of differences in response between arteries and veins, and some degree of selectivity between vascular territories, but the goal of much more specific or localized vasodilation has not been achieved. The most prominent difference between the three main classes of antihypertensive drugs is the mild reflex increase of heart rate seen with the dihydropyridines and the bradycardia seen with verapamil. Most of the side effects of calcium antagonists are also based on vasodilatation, such as flushing and headache. The mild edema often seen with the dihydropyridines probably depends on the changes in capillary pressure brought about by arterial dilatation. Despite their undoubted efficacy as vasodilators, there are no studies thus far which allow any conclusions as to the long-term effect of calcium antagonists on the morbidity and mortality due to hypertension.
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PMID:Clinical pharmacology of calcium antagonists. 202 57

Sudden hypertensive surges are often observed in patients with primary hypertension. Even though the possibility of a pheochromocytoma almost automatically comes to mind, this diagnosis is confirmed only in a few patients (less than 1%). The case of a 55 yr old patient with very high posture-or emotion-induced hypertensive paroxysms, often associated with chest pain and flushing is described. All laboratory tests were normal except for plasma catecholamines, which were high especially during stress tests (Tab. II). The existence of a pheochromocytoma was excluded on the basis of repeatedly normal urinary catecholamine levels after hypertensive crises and a negative CT abdominal scan and I131 MIBG adrenal scintigraphy. An alteration of the baroreceptor reflex was ruled out, as the blood pressure response to autonomic function tests was normal. The cause of the orthostatic hypertensive crises could not be attributed to hypovolemia, as plasma volume proved normal. Measurement of circulating catecholamines showed elevated free plasma epinephrine with low conjugated epinephrine indicating a defective conjugation of this amine. This finding suggests an injured inactivation of epinephrine and might be involved in the pathogenesis of the hypertensive crises observed. Continuous intra-arterial blood pressure monitoring demonstrated the existence of mild hypertension with a normal 24-hour blood pressure pattern. However, the tracings were interspersed with numerous blood pressure peaks. Average 24 hour blood pressure was normalized by the therapy, but the hypertensive crises were not controlled by any of the drugs used. The absence of target organ damage despite the spectacular rises in blood pressure suggests that the cardiovascular system is well able to withstand hypertensive episodes if they are short lived.
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PMID:["Essential" hypertension with extreme pressure variability. Description of a case and considerations]. 207 89

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.
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PMID:Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 208 13

Calcium antagonists, particularly those derived from the dihydropyridine class, have shown remarkable efficacy in the treatment of hypertension and other cardiovascular disorders. This review will concentrate on the use of one of the newer compounds in this category, isradipine, in the treatment of arterial hypertension. Isradipine is a calcium antagonist with marked vascular selectivity and, in practical terms, is devoid of cardiac effects. Its usefulness in hypertension is well documented, both when used as single drug treatment and in combination with other agents, particularly beta-blockers. Isradipine is well tolerated, does not cause metabolic disturbances and, apart from the typical dihydropyridine-type vascular adverse effects, e.g. flushing and ankle oedema, it does not cause any specific side effect. Some results obtained with isradipine in animal studies, e.g. the antiatherosclerotic effect and the brain tissue preserving effect seen in experimental stroke, appear to hold great promise for future important clinical applications for isradipine.
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PMID:Isradipine in hypertension. 215 Jun 33

The calcium antagonists of the dihydropyridine group, isradipine and nifedipine, were compared in 64 patients with mild to moderate hypertension (diastolic blood pressure 95 to 110mm Hg). A 2-week placebo run-in phase was followed by a double-blind crossover trial comprising two 3-week treatment periods with either calcium antagonist. The (fixed) dosages were isradipine 2.5mg twice daily and nifedipine retard 20mg twice daily. Blood pressure (systolic/diastolic) at baseline was 155/101mm Hg and decreased significantly by 14%/15% on isradipine and by 11%/12% on nifedipine (difference between treatments not significant). The drugs differed significantly with regard to incidence of adverse effects (mostly flushing and headache); the total rates were 16% on isradipine and 36% on nifedipine. At the end of the trial, patients were asked which drug or treatment phase they preferred. Isradipine was preferred by 50% of patients; only 20% preferred nifedipine. Thus, it is concluded that isradipine, administered in an equally effective antihypertensive dosage regimen is superior to nifedipine with regard to the incidence of adverse effects, resulting in greater patient satisfaction with treatment.
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PMID:The calcium antagonist isradipine in the therapy of hypertension. A double-blind crossover comparison with nifedipine. 215 Jun 44

Fluosol, a perfluorcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, Fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non small cell carcinoma of the luing. Fifty patients were enrolled in the study which was closed for accrual in November 1987. Five patients were withdrawn prior to the institution of radiation: one patient diagnosed with bone metastasis and four patients withdrawn due to mild to moderate reactions to Fluosol. Of the 49 patients administered Fluosol, 34 mild to moderate adverse reactions were noted in 22 patients to either the test dose/infusion (16 reactions including withdrawn patients) or post infusion (18). Flushing, dyspnea and hypertension (test dose/infusion) and chills and/or fever (postinfusion) were the typical symptoms. Transient elevation of blood chemistries (SGOT, SGPT, alkaline phosphatase, BUN) were noted in some patients. Six patients had transient depression of WBC counts (toxicity scores of 1 or 2) and two patients had transient depression of platelets (toxicity score of 1). None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diangosed with metastatic disease during therapy and three patients died of their disease during treatment. One patient was withdrawn due to ineligibility and one patient withdrawn due to moderate reactions to Fluosol during the 3rd and 4th infusions. The total dose of Fluosol was escalated from 42 mL/Kg to 49 mL/Kg in 5, 6, or 7 weekly infusions. Patients breathed 100% oxygen for a minimum of one-half hr prior to and during radiation treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy. Seventeen of 34 patients (50%) achieved a complete response to treatment and 11 patients (32%) had a partial response. Thirteen patients remain alive (range of 12 to 20 months) including 10 of 17 complete responders, 2 of 11 partial responders, and 1 treated with chemotherapy postradiation. The median absolute survival time of the patients completing therapy was 15.5 months and the 12 and 18 month absolute survival rates were 81% and 74%, respectively. The 45 patients starting protocol therapy had a median absolute survival of 9.2 months with a 12-month and 18-month survival of 45% and 35%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: results of a phase I/II study. 216 21

Diethyldithiocarbamate (DDTC), a heavy metal-chelating agent, has been shown to decrease cisplatin (CP) toxicity in preclinical studies. This phase I dose-escalation study was undertaken to investigate DDTC as a chemoprotector in patients with advanced cancer. Thirty-five courses of CP in doses ranging from 120 to 160 mg/m2 were given intravenous (IV) bolus to 19 patients. DDTC at 4 g/m2 was infused over 1 hour, starting 45 minutes after CP. There was minimal nephrotoxicity with a mean creatine clearance of 99 mL/min +/- 4 pretreatment and 86 mL/min +/- 4 on day 21. Two courses were associated with a WBC count less than 2,000/mm3 and one course with a platelet count of 15,000/mm3. Two patients had grade 2 neurotoxicity. Hearing loss occurred in 11 patients: five greater than or equal to 20 dB, five greater than or equal to 40 dB, and one greater than or equal to 60 dB. All patients who received cranial irradiation had ototoxicity compared with 43% of those without radiation (P less than .05). All patients experienced toxicity during the DDTC infusion, including hypertension, flushing, diaphoresis, agitation, and local burning. We conclude that DDTC can protect against CP nephrotoxicity at doses up to 160 mg/m2. Ototoxicity became the dose-limiting factor.
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PMID:Modification of cisplatin toxicity with diethyldithiocarbamate. 164


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