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 Of the 60 patients entering the study, one died of unexplained staphylococcal septicaema, two were withdrawn for non drug-related reasons and 14 (32%) were withdrawn because of adverse effects on active therapy (headaches, facial flushing, leg oedema, chest pain, dizziness). 6.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

The serotonergic antagonist ketanserin (K) was compared to nifedipine (N) in a five-center international study on hypertensive patients over the age of 50 years. After a 4-week placebo run-in period, patients were randomly assigned to receive for 3 months either ketanserin (40 mg b.i.d. after 2 weeks of 20 mg b.i.d.) or nifedipine (20 mg N retard b.i.d.). After 1 month, monotherapy patients whose blood pressure was not sufficiently reduced received a diuretic in combination therapy. At the end of the active treatment period, patients who had remained on monotherapy received placebo until hypertension returned or for a maximum of 2 months. One hundred and seventeen patients were entered in the study, 58 on K and 59 on N. More patients switched to combination with a diuretic in the K group (14 patients) than in the N group (6 patients). The overall reduction in blood pressure was similar for K and N. Total response rate was high (96%) for the two drugs. Blood pressure was reduced both at peak and trough drug levels. No orthostatic reactions were observed, and no rebound hypertension occurred at discontinuation of therapy. Ketanserin monotherapy slightly decreased heart rate (-1 beats/min). whereas N produced a significant increase (+6 beats/min). Body weight significantly increased with K (+1.1 kg) and was unchanged with N. More patients complained of adverse reactions during N monotherapy (47%) than during K monotherapy (34%). Flushing and leg edema were more frequent with N.
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PMID:Ketanserin versus nifedipine in the treatment of essential hypertension in patients over 50 years old: an international multicenter study. 244 56

Excessive accumulation of intracellular calcium in Duchenne muscular dystrophy (DMD) may be a necessary step in the process that causes muscle damage in this disease. Because of this possibility, a controlled trial of the calcium channel blocking agent nifedipine was undertaken. One hundred and five patients were randomized and treated in a double-blind manner for 18 months. Muscle strength, contractures, functional ability, cardiopulmonary changes, and laboratory data were monitored. The dose of nifedipine was 0.75-1 mg/kg/day in the first 6 months and 1.5-2 mg/kg/day for the next 12 months. Satisfactory blood levels of nifedipine were attained. The study had a power greater than 0.99 to detect a slowing of the illness to 25% of its original rate of progression. No significant improvement was demonstrated in the treated group. One or more of the frequent mild side effects of flushing, dizziness, and leg edema, often associated with the use of nifedipine in adults, occurred transiently in approximately one-half of the patients in the nifedipine group and in 21% of the placebo group. Four patients died, two on nifedipine and two on placebo. This study demonstrates that nifedipine is safe to administer in children, but that it is without beneficial effect on the course of DMD.
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PMID:Clinical investigation in Duchenne dystrophy. VI. Double-blind controlled trial of nifedipine. 355 Apr 55

A 65-year-old female was admitted with leg edema by retroperitoneal fibrosis and tricuspid valve incompetence by fibrosis, cutaneous fibrosis, moderate flushing over the upper body without diarrhea. It revealed an ileal carcinoid tumor with hepatic metastases. Octreotide (Sandostatine), tumor excision and interferon alpha 2b treatment led to a regression of flushing and edema, a reduction of fibrosis and a stabilization of the metastatic carcinoid, with normal serotonin levels.
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PMID:[Edema caused by retroperitoneal and tricuspid fibrosis with sclerodermatous cutaneous involvement disclosing carcinoid tumor. Apropos of a case and review of the literature]. 918 47

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.
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PMID:Treatment of hypertensive children with amlodipine. 1104 Nov 59

Bosentan, a dual endothelin receptor antagonist, is indicated for the treatment of patients with pulmonary arterial hypertension (PAH). Following oral administration, bosentan attains peak plasma concentrations after approximately 3 hours. The absolute bioavailability is about 50%. Food does not exert a clinically relevant effect on absorption at the recommended dose of 125 mg. Bosentan is approximately 98% bound to albumin and, during multiple-dose administration, has a volume of distribution of 30 L and a clearance of 17 L/h. The terminal half-life after oral administration is 5.4 hours and is unchanged at steady state. Steady-state concentrations are achieved within 3-5 days after multiple-dose administration, when plasma concentrations are decreased by about 50% because of a 2-fold increase in clearance, probably due to induction of metabolising enzymes. Bosentan is mainly eliminated from the body by hepatic metabolism and subsequent biliary excretion of the metabolites. Three metabolites have been identified, formed by cytochrome P450 (CYP) 2C9 and 3A4. The metabolite Ro 48-5033 may contribute 20% to the total response following administration of bosentan. The pharmacokinetics of bosentan are dose-proportional up to 600 mg (single dose) and 500 mg/day (multiple doses). The pharmacokinetics of bosentan in paediatric PAH patients are comparable to those in healthy subjects, whereas adult PAH patients show a 2-fold increased exposure. Severe renal impairment (creatinine clearance 15-30 mL/min) and mild hepatic impairment (Child-Pugh class A) do not have a clinically relevant influence on the pharmacokinetics of bosentan. No dosage adjustment in adults is required based on sex, age, ethnic origin and bodyweight. Bosentan should generally be avoided in patients with moderate or severe hepatic impairment and/or elevated liver aminotransferases. Ketoconazole approximately doubles the exposure to bosentan because of inhibition of CYP3A4. Bosentan decreases exposure to ciclosporin, glibenclamide, simvastatin (and beta-hydroxyacid simvastatin) and (R)- and (S)-warfarin by up to 50% because of induction of CYP3A4 and/or CYP2C9. Coadministration of ciclosporin and bosentan markedly increases initial bosentan trough concentrations. Concomitant treatment with glibenclamide and bosentan leads to an increase in the incidence of aminotransferase elevations. Therefore, combined use with ciclosporin and glibenclamide is contraindicated and not recommended, respectively. The possibility of reduced efficacy of CYP2C9 and 3A4 substrates should be considered when coadministered with bosentan. No clinically relevant interaction was detected with the P-glycoprotein substrate digoxin. In healthy subjects, bosentan doses >300 mg increase plasma levels of endothelin-1. The drug moderately reduces blood pressure, and its main adverse effects are headache, flushing, increased liver aminotransferases, leg oedema and anaemia. In a pharmacokinetic-pharmacodynamic study in PAH patients, the haemodynamic effects lagged the plasma concentrations of bosentan.
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PMID:Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. 1556 89