Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 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 Of the 60 patients entering the study, one died of unexplained staphylococcal septicaema, two were withdrawn for non drug-related reasons and 14 (32%) were withdrawn because of adverse effects on active therapy (headaches, facial flushing, leg oedema, chest pain, dizziness). 6.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 acute hypotensive effect of nifedipine was evaluated, and the possibility of its long-term use in hypertensives over 60 years of age was studied. Sublingual nifedipine in a dose of 20 mg was given to 28 patients, mean age 73.1 yrs, and blood pressure, heart rate, and plasma drug concentration were monitored at 15 min, and every 30 min thereafter for 3 hrs. Systolic and diastolic blood pressure decreased at 15 min by 22.1 and 7.0 mmHg, respectively, reaching a maximal decrease two hours after drug administration. The decrease in blood pressure level did not correlate with nifedipine plasma concentration, but only with the initial systolic blood pressure. Long-term treatment with nifedipine was initiated in 60 patients, with 45 patients completing the study. Mean age was 66.2 years. An initial dose of 30 mg daily had to be increased to 60-80 mg in one-third of the patients. Monotherapy was not satisfactory in some patients. Blood pressure gradually decreased from 173/99 to 148/85 mmHg at three months, and to 141/84 mmHg at six months. Drug tolerance was fairly good. Nifedipine was withdrawn due to a considerable increase in heart rate in three patients and skin allergy in one. The most frequent adverse symptoms were: rash, headache, and leg oedema. Laboratory tests revealed no changes in urea and creatinine, and an increase in fasting glycaemia. Lipid parameters did not change significantly. These data proved that a single dose of 20 mg of nifedipine produced therapeutic plasma concentration of the drug and good hypotensive effect, positively correlating with initial systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and long-term treatment of hypertension with nifedipine in the elderly. 225 86

1. To test whether nifedipine reduces corticosteroid requirements of patients with asthma, a 16-week double-blind crossover trial comparing nifedipine with placebo was performed. 2. Eight females and seven males with corticosteroid-dependent asthma were studied, ranging in age between 20 and 65 years (mean = 45 years). 3. Results showed that in 12 of 15 patients, nifedipine caused significant reduction in corticosteroid requirements when compared with placebo (P less than 0.01). No side-effects were reported apart from mild headache and leg oedema observed in a few patients receiving nifedipine. 4. It could be concluded that nifedipine has a steroid-sparing effect in steroid-dependent asthma.
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PMID:Nifedipine in corticosteroid-dependent asthma: preliminary study. 268 Jan 86

The use of nisoldipine (10-20 mg b.i.d.) was evaluated as a replacement therapy for long-acting nifedipine (40-120 mg/day) in 21 patients with severe hypertension, who were resistant to or intolerant of nifedipine. Except for one patient with specific contraindications, all participants received an individually determined constant dose of beta blocker throughout the 8-month study. Results indicated a significant decrease in blood pressure after four weeks of treatment with nisoldipine (173 +/- 5/98 +/- 4 to 156 +/- 3/91 +/- 2 mmHg, p less than 0.05) without an associated change in pulse rate in 19 patients; only 5 of the 21 patients showed no further benefit from nisoldipine. No significant biochemical changes were noted in any of the patients during the study. In three patients, leg edema that had developed as a consequence of previous nifedipine therapy resolved completely following nisoldipine administration. Two patients withdrew from the study before term because of headaches and palpitations. An additional two patients suffered headaches, but tolerated the drug and continued the study. One patient suffered from polyuria. Nisoldipine appears to be an effective substitute treatment for nifedipine in severely hypertensive patients sensitive or resistant to nifedipine.
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PMID:Nisoldipine: a replacement therapy for nifedipine in the treatment of severe hypertension. 338 70

The safety and tolerability of mibefradil, a selective T-type calcium channel antagonist, were evaluated in 3,430 patients with essential hypertension and chronic stable angina pectoris treated in 15 double-blind placebo and active-controlled clinical trials and 2 open-label, long-term safety studies. Of these patients, 2,636 were treated with the recommended doses of mibefradil (50 and 100 mg) and form the basis of this report. With the 50-mg dose of mibefradil, the incidence of each adverse event was similar to, or lower than, that observed in the placebo-treated patients. Treatment with the 100-mg dose was associated with a slightly higher incidence compared to placebo of dizziness (2.1% vs 1.8%), leg edema (3.5% vs 1.4%), fatigue (2.1% vs 1.4%), and lightheadedness (2.1% vs 0.4%). The incidence of headache (4.6%) and angina pectoris (1.1%) was more frequent in patients treated with placebo. In active-controlled trials, a lower incidence of pedal edema (5.1%) was observed with mibefradil compared to amlodipine (25.7%), diltiazem SR/CD (9.4%), or nifedipine SR/GITS (17.4%). Overall, mibefradil was better tolerated than amlodipine and nifedipine SR/GITS and was as well tolerated as diltiazem SR/CD. Rates of premature discontinuation due to clinically adverse experiences with the 50- and 100-mg doses were 2.5% and 3.5%, respectively, compared with placebo (3.5%). No consistent pattern of laboratory adverse experiences were observed for mibefradil. Sinus bradycardia (heart rate <45 beats/minute) and first-degree atrioventricular block were the only relevant treatment-emergent electrocardiographic changes that occurred more frequently with mibefradil than with placebo. No evidence of first-dose effects was observed in mibefradil-treated patients, and withdrawal effects were not observed in clinical trials. There were no clinically important differences in safety profiles in the demographic subgroups for age, gender, or race. The results of this comprehensive safety analysis indicate that treatment with the recommended doses of mibefradil is well tolerated and safe.
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PMID:Safety of mibefradil, a new once-a-day, selective T-type calcium channel antagonist. 928 53

Mibefradil is the prototype of a new class of calcium antagonists that selectively block T-type voltage-gated plasma membrane calcium channels in vascular smooth muscle. The drug is structurally and pharmacologically different from traditional calcium antagonists. It does not have negative inotropism at therapeutic concentrations, and is not associated with reflex activation of neurohormonal and sympathetic systems. In clinical studies of hypertension, mibefradil 50 and 100 mg/day reduced trough sitting diastolic and systolic blood pressures in a dose-related manner. Dosages exceeding 100 mg/day generally did not result in significantly greater efficacy, but were associated with a higher frequency of adverse events. No first-dose hypotensive phenomenon was observed. Mibefradil has antiischemic properties resulting from dilation of coronary and peripheral vascular smooth muscle, and a slight reduction in heart rate. In clinical studies of chronic stable angina pectoris, dose-related increases in exercise duration, time to onset of angina, and time to 1-mm ST-segment depression during exercise tolerance tests occurred. Mibefradil reduced the number and duration of ischemic events recorded by 48-hour ambulatory electrocardiograph (ECG) monitoring, as well as number of anginal episodes and nitroglycerin consumption. Favorable hemodynamic and clinical profiles are reported, including high trough:peak ratios (> 80%), high oral bioavailability, and long elimination half-life (17-25 hrs) permitting once/day dosing. Dizziness, headache, leg edema, and lightheadedness are frequently reported, but overall the agent is well tolerated. First-degree atrioventricular block and sinus bradycardia are the most frequent ECG changes caused by the drug. In vitro studies indicate mibefradil inhibits cytochrome P450 1A2, 2D6, and 3A4, resulting in elevated plasma concentrations of drugs metabolized by those isoenzymes. Therefore, it is contraindicated in patients receiving terfenadine, astemizole, cisapride, lovastatin, or simvastatin.
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PMID:Mibefradil, a pharmacologically distinct calcium antagonist. 962 98

An 8-week, randomized, double-blind study comparing the efficacy and tolerability of policosanol and acipimox was conducted in patients with type II hypercholesterolemia. Prior to entry into active treatment, all patients followed a standard cholesterol-lowering diet for 12 weeks. Sixty-three patients were randomized to receive either policosanol (10 mg/day) or acipimox (750 mg/day) tablets for 8 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly reduced total cholesterol (p < 0.0001) (15.8%), low-density lipoprotein (LDL)-cholesterol (21%) and the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (15.8%) and cholesterol to HDL-cholesterol (11.5%). Acipimox significantly lowered both cholesterol and LDL cholesterol by 7.5%. The percent changes of total cholesterol, LDL-cholesterol and both ratios were larger in the policosanol group than in the acipimox group. Both drugs were well tolerated. Acipimox significantly increased (p > 0.001) aspartate amino transferase levels but only four patients showed increases above the normal limit. Policosanol significantly reduced creatinine values (p > 0.05) but no patients had values out of the normal range. Four patients withdrew from the study (two from each group) but none withdrew because of adverse effects. No adverse effects were reported in the policosanol group, while five patients on acipimox reported adverse effects (hot flushes, nausea, vomiting, headache, hypochondrial pain and leg edema). These results indicate that policosanol (10 mg/day) was more effective and well tolerated than was acipimox (750 mg/day) in this study population.
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PMID:A comparative study of policosanol Versus acipimox in patients with type II hypercholesterolemia. 1064 16

A 31-yr-old man presented with a 1-wk history of fever, chills, weakness, headaches, and a significant 20-lb weight loss over the preceding 2 months. His past medical history was relevant for liver amebiasis during childhood. Two days before admission, the patient noticed jaundice. He denied abdominal pain or other GI symptoms, and there was no history of alcohol intake, medications, or illicit drugs. His physical examination revealed generalized jaundice, hepatosplenomegaly, and bilateral leg edema. Neurologically, the patient was agitated, with periods of disorientation, and he had bilateral flapping. His blood tests revealed pancytopenia, renal failure, liver failure, and coagulopathy. Because the patient had a fever, hepatosplenomegaly, and pancytopenia, a further workup also included a bone marrow and liver biopsy. No conclusive diagnosis could be made from the above tests, and the patient died 5 days after admission. Postmortem evaluation, including flow cytometry and gene rearrangement in the tissue obtained from the liver, revealed large B cell lymphoma. This case illustrates an unusual presentation of hepatic non-Hodgkin's lymphoma. Current information regarding this entity is scant, mainly owing to its rarity. We present a review of the literature, including the incidence, presentation, treatment, and prognosis of primary hepatic lymphoma.
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PMID:Primary hepatic non-Hodgkin's lymphomas: case report and review of the literature. 1468 34

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

Orbital infarction syndrome is defined as ischemia of global intraorbital structures such as extraocular muscles, optic nerves, and retina. The most common cause of this syndrome is carotid arterial occlusion. Other causes include vasculitis, vasospasm, and compression of intraorbital circulation. There has never been reported a case of orbital infarction syndrome in nephrotic syndrome patient. We present a case of 42-year-old Thai man with underlying disease nephrotic syndrome presented with abrupt onset of headache at left temporal area, horizontal diplopia, limitation of eye movement in all directions, ptosis, and blurred vision on the left eye. He was treated with pulse methylprednisolone intravenously for 3 days. Leg edema was improved however, the eye symptoms persisted. There was no evidence of hypercoagulable state. Magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) revealed loss of signal intensity at left internal carotid artery from base of skull to intracavernous part. Cerebral angiography demonstrated complete occlusion of left common carotid artery. After the anticoagulant treatment, his symptoms were gradually improved. The cause of extensive carotid arterial occlusion in this patient is most likely from hypercoagulable state. Although it was negative for hypercoagulable state evidence, the authors assume that the high dose steroid treatment could lead to remission of nephrotic syndrome and resulting in the resolution of hypercoagulable state.
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PMID:Orbital infarction syndrome in nephrotic syndrome patient with extensive carotid arteries occlusion. 1818 41


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