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)

We report a case of renovascular hypertension associated with neurofibromatosis complicated by moderate proteinuria. A 16-year-old female was admitted to Kensei General Hospital with a complaint of headache and a blood pressure of 230/120 mm Hg. She was referred to us for further evaluation of the hypertension. On examination, cafe-au-lait spots were seen over her extremities and flank, and a bruit was heard in the right upper abdomen. The urinary protein excretion was 2.1 g/day. The plasma renin activity (PRA) and plasma aldosterone concentration were high, but the levels of catecholamines were normal. The renogram was asymmetric and on venous sampling, the PRA in the right renal vein was 58.3 ng/ml/h and that in the left was 22.1 ng/ml/h. CT scan detected an approximately 10-mm mass in the proximal right renal artery. Arteriography disclosed severe stenosis in the right renal artery and the superior mesenteric artery. Therefore, we concluded that her hypertension resulted from stenosis of the right renal artery due to neurofibromatosis. Accordingly, she underwent an operation to reconstruct that artery. After the operation, her blood pressure and PRA normalized without administration of any anti-hypertensive drug and urinary protein disappeared.
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PMID:A case of renovascular hypertension associated with neurofibromatosis. 873 Apr 48

The pharmacokinetics and safety of a novel, long-acting, prodrug-type K(+)-channel opener, Y-27152, were investigated in healthy male volunteers. In the first phase, single oral doses of 0.1, 0.25, 0.5, 0.75, and 1.0 mg of Y-27152 (n = 3-6 per dose) were given after overnight fasts in a dose-escalating manner. The 0.75-mg dose was given both after an overnight fast or after food to examine the effects of food intake. In the second phase, multiple doses of Y-27152 were taken after meals once daily for 7 consecutive days. In part A of this phase, either placebo (n = 3) or 0.5 mg of Y-27152 (n = 6) was taken for 7 days, and in part B of this phase 0.5-, 0.75-, and 1.0-mg doses were taken in a dose-escalating manner for 1,3, and 3 days, respectively (n = 9). In the single-dose study, peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of main active metabolite (Y-26763; M1) increased in parallel with dosage. This dose-linearity was less obvious with Y-27152, which had an AUC approximately 6 to 10 times less than that of M1. Administration with food at 0.75 mg resulted in a small but significant decrease (approximately 10%) in the Cmax and AUC of M1. At doses of 0.5 mg or higher, participants experienced headaches and palpitations, which were probably due to the vasodilatory effects and did not require treatment. Mean diastolic blood pressure significantly decreased and pulse rate increased at doses of 0.5 mg or higher compared with predose values. Plasma renin activity was significantly elevated 4 hours after the administration of the 0.75- and 1.0-mg doses, but showed no significant change at 0.5 mg. In the multiple-dose study, the time profile of the plasma concentration of M1 approximately coincided with the simulation curves worked out using the pharmacokinetic parameters obtained in the singledose study. The incidence of headaches tended to increase with dose in part B, but drug administration was not discontinued in any case. Plasma renin activity again increased 4 hours after administration. In phase B of the multiple-dose study, diastolic blood pressure decreased and pulse rate increased compared with predose values. Y-27152 was metabolized to M1 and well tolerated in healthy volunteers, and its pharmacologic effects were likely caused by vasodilation, which could make it an effective antihypertensive agent.
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PMID:Pharmacokinetics and safety of a novel, long-acting, prodrug-type potassium channel opener, Y-27152, in healthy volunteers. 873 23

The antihypertensive efficacy of calcium antagonists could depend on the concentration of circulating renin. To investigate this hypothesis, 102 hypertensive men or women were included in this study. After an initial 2 week placebo period, the patients were administered slow-release nicardipine, 50 mg twice a day for twelve weeks. The blood pressures were measured with a mercury sphygmomanometer at inclusion (S2) and after 12 weeks of treatment (S14), in addition to home automeasure during the week before inclusion and the two weeks preceding the final visit. The plasma renin activity (RA) was measured at S2 and S14. Its value at inclusion was used to differentiate patients with low renin (< or = 11 ng/l) from those with normal (> 11 < or = 17 ng/l) or high renin activity (> 17 ng/l). The blood pressure measured by sphygmomanometer or automeasure was significantly lower at the end of the active treatment period (SBP: -8 mmHg; DBP: -9.5 mmHg; and SBP: -5.8 mmHg; DBP: -5.7 mmHg respectively); the reduction in blood pressure was significantly higher in the group with low RA than in the group with high RA. The reductions in SBP measured in the morning and evening and in DBP measured in the morning were significantly greater in the group with low RA than in the group with high RA. The reduction of SBP measured in the morning at midday, and in the evening was correlated to the basal value of RA. Mild side effects were observed in 20 patients leading to the interruption of treatment in 11 cases because of headache. The best antihypertensive response is observed in patients with low plasma RA. This could explain the good response to calcium antagonists usually observed in elderly hypertensives.
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PMID:[Relation between plasma renin level and antihypertensive response to nicardipine]. 874 14

A double-blind, randomized, three-way complete crossover study was carried out to compare pharmacodynamic effects and tolerability during a 24-h intravenous infusion of ITF 296, isosorbide dinitrate (ISDN), and placebo, in the supine position and during 70 degrees head-up tilt. Ten healthy men aged 21-34 years participated in the study to obtain complete data in nine. Dosing started at 1 microgram/kg/min and was titrated up during the first 30 min of infusion, to produce a 10% reduction in diastolic blood pressure (DBP). At least 6 days elapsed between consecutive treatments. Heart rate (HR) and blood pressure were measured at least half hourly throughout the infusion period and up to 2 h afterwards. Systolic time intervals were measured before and at 0.5, 1, 2, 3, and 24 h of infusion in the fasting state. Tilt tests (70 degrees head-up for 2 min) were performed at 1, 6, 12, and 24 h of infusion. From 60 min before tilt, during tilt, and up to 15 min after end of tilt, ECG was monitored and BP, HR, and b/a ratio were recorded by means of fingertip plethysmography. Plasma-renin activity and concentrations of epinephrine and norepinephrine were measured preinfusion, and before and after tilt tests. Subjects were questioned frequently about adverse events. General tolerability of ISDN in the nine subjects who completed the study was poor, with eight suffering from headache and four from symptoms suggesting postural hypotension during tilt tests. Tolerability of ITF 296 was better, with 5 of 10 subjects reporting headache and 2 of 10 symptoms of postural hypotension during the first tilt only. Both active treatments successfully reduced DBP by at least 10% in all subjects at similar dose levels (final infusion rates 2.8 and 2.3 micrograms/kg/min for ITF 296 and ISDN, respectively). Systolic blood pressure (SBP) was reduced by about 6-7 mm Hg by both treatments. HR was increased by about 5 beats/min by ISDN but not by ITF 296. Those changes in BP and HR persisted throughout the 24-h infusion and reversed when it was discontinued. Fingertip plethysmography showed a profound reduction of b/a ratio, which persisted throughout the 24-h infusion. ISDN had consistently greater effects than ITF 296, suggesting that ISDN has the greater effects on small arterial vessels. Both active treatments reduced QS2 index throughout the 24-h period. Both treatments also reduced left-ventricular ejection time (LVET) index up to 3 h of infusion, with ISDN having the greater effects on LVET index and ITF 296 being intermediate between ISDN and placebo. ISDN prolonged pre-ejection period (PEP) at 1 h, had no effect at 2 h, and shortened PEP at 3 and 24 h. ITF 296 decreased PEP consistently during the 24-h infusion. Plasma-renin activity, epinephrine, and norepinephrine were increased by ISDN substantially more than by ITF 296. These results show that both ITF 296 and ISDN had comparable effects on diastolic blood pressure at similar dose-levels. ISDN increased HR, whereas ITF 296 did not. b/a Ratio was reduced more by ISDN, suggesting a greater activity on small arterial vessels. Arterial effects were maintained throughout the 24-h infusion. ISDN had a greater effect on venous return than ITF 296. ITF 296 seemed to show more balanced effects on preload and afterload than ISDN. ISDN caused significantly greater neurohumoral counter-regulation than ITF 296. Hemodynamic response to tilt was attenuated, as judged by the fact that hypotension occurred only during the early hours of the infusion, but the variability in the response of BP to tilt does not allow any firm conclusions to be drawn about possible development of tolerance. Tolerability of ISDN was poor and that of ITF 296 was better.
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PMID:Hemodynamic and humoral effects at rest and after head-up tilt tests during 24-hour infusion of a new nitrate ester, ITF 296, compared with ISDN and placebo in healthy volunteers: a double-blind, randomized, within-subject study. 883 31

Systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations. However, renovascular hypertension (RVH) has been rarely reported in these patients. We describe here a 49-year-old female with antiphospholipid antibodies, complicated with RVH and presenting with sudden onset of severe hypertension, headache and nausea. She had experienced phlebitis and arterial thrombosis of the right leg. At the age of 38 years, she was diagnosed as SLE and steroid therapy was started, but she had poor drug compliance and irregularly visited our clinic. On admission, hypertension was recognized and abdominal bruit was audible on physical examination. Serological findings were compatible with SLE. She was also found to have IgG anti-cardiolipin antibody and lupus anticoagulant. Peripheral plasma renin activity (PRA) was elevated, and captopril test showed hyper-response of PRA with lowering of blood pressure. Renal echography and scintigram showed a small and poorly perfused right kidney. Selective angiography demonstrated a severe stenosis of the right renal artery at origin. A stenosis at the origin of both the superior mesenteric artery (SMA) and celiac trunk was also detected. Percutaneous transluminal angioplasty was performed, achieving successful dilatation of the right renal artery and SMA, whereas the attempt to insert the catheter into the celiac trunk was unsuccessful. After this procedure, abdominal bruit has not been audible. Following the initiation of steroid pulse therapy combined with heparin and dipyridamole, her blood pressure was gradually depressed and the test for lupus anticoagulant became negative. Therefore, RVH of this patient is thought to be associated with antiphospholipid antibodies.
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PMID:[Renovascular hypertension associated with antiphospholipid antibodies in a woman with systemic lupus erythematosus]. 891 95

A juxtaglomerular cell tumor (JGCT) was found in the right kidney of a 17-year-old female who had suffered from a headache of 1-year duration and hypertension. CT and US were diagnostic in association with determination of plasma renin activity. Light and electron microscopic, immunohistochemical, and flow cytometric investigation of the resected tumor confirmed the diagnosis of JGCT with demonstration of ultrastructural features and distribution pattern of characteristic secretion granules of various sizes and shapes, coexistence of mast cells within the tumor (JGCT cells/mast cells = 10), and perivascular architecture.
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PMID:Juxtaglomerular cells tumor of the kidney: a case report with electron microscopic and flow cytometric investigation. 909 31

Candesartan cilexetil is rapidly and completely hydrolysed to the active compound candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, long-acting, selective angiotensin II AT1 receptor blocker. The pharmacokinetics of candesartan were investigated after single and repeated once-daily doses of candesartan cilexetil in the dose range 2-16 mg in both younger (19-40 years) and elderly (65-78 years) healthy volunteers in five studies. Blood pressure, heart rate, and hormones associated with the renin-angiotensin system, and safety of candesartan cilexetil administration were also assessed. Placebo comparisons were made in four studies. Frequent blood samples were collected after the first single dose of candesartan cilexetil, and during the last dosing interval after 1 week repeated once-daily administration. Serum and plasma were analysed for candesartan cilexetil, candesartan and its inactive metabolite, CV-15959, as well as angiotensin I and II, aldosterone, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity. The AUC and Cmax of candesartan showed dose-proportional increases in the dose range of 2-16 mg candesartan cilexetil after both single and repeated once-daily tablet intake, indicating linear pharmacokinetics in both younger and elderly healthy subjects. The pharmacokinetics did not change on repeated dosing and, as expected from the half-life of candesartan of approximately 9 h in younger subjects, there was almost no accumulation after repeated once-daily dosing. The time to peak candesartan concentrations after tablet intake was consistently approximately 4 h at all dose levels. Both Cmax and AUC of candesartan were increased after single and repeated once-daily dosing in the elderly compared to younger subjects by approximately 50%. However, no accumulation after repeated once-daily dosing were seen in the elderly. The half-life of candesartan in the elderly (9-12 h) was somewhat longer than in the younger healthy adult volunteers (approximately 9 h) and no gender-related differences in the disposition of candesartan were observed. Serum concentrations of CV-15959 were much lower than candesartan, and reached peak serum concentrations later, about 4-9 h after dose intake. The elimination of CV-15959 was somewhat slower than that of candesartan. Candesartan cilexetil, the prodrug to candesartan, was not measurable in serum. No differences in ACE activity or serum aldosterone concentrations were observed between subjects receiving candesartan cilexetil and placebo tablets. Plasma angiotensin I and II concentrations and PRA were augmented after single doses and further increased after 1 week repeated candesartan cilexetil dosing. Single and repeated doses of candesartan cilexetil were well tolerated in the younger and elderly volunteers. Only mild adverse events were recorded, with 'headache' as the most commonly reported event, and no increase in the number of reported adverse events was observed with higher doses of candesartan cilexetil. No clinically significant changes in respect to vital signs, physical examination, ECG, and clinical laboratory tests were observed.
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PMID:Pharmacokinetics of candesartan after single and repeated doses of candesartan cilexetil in young and elderly healthy volunteers. 933 Oct

Renal artery stenosis or occlusion causing the hyponatremic-hypertensive syndrome has been rarely reported. Our impression, however, was that the disorder is not uncommon. Case records from patients in one city (population 350 000) presenting between 1980 and 1997 with hypertension, hyponatremia, and evidence of renal ischemia were scrutinized. Thirty-two patients fulfilling inclusion criteria were identified. Admission supine arterial pressures were high (mean 228/124 mm Hg), but there was a vigorous fall in pressure on standing (26/12.7 mm Hg recorded in 27 patients). Mean plasma concentrations of sodium (129.7 mmol/L) and potassium (2.7 mmol/L) were low, and 24-hour urine protein excretion was elevated in 19 of 26 patients. Twenty-two of the 32 patients were female, the majority were asthenic, and all but 5 were smokers. Symptoms precipitating hospitalization were headache, clouding of consciousness, confusion, weakness, weight loss, thirst, and polyuria. Plasma renin levels, measured in 20 patients, were elevated in most cases and correlated inversely (r=-0.63, P<0.01) with the plasma sodium concentration. The hyponatremic-hypertensive syndrome in patients with renal ischemia is not rare: Rather, it is underreported. It tends to affect elderly asthenic women who smoke heavily. Stimulation of renin release from the ischemic kidney is probably central to the pathophysiology. The syndrome deserves better recognition to ensure appropriate investigations and management.
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PMID:Hyponatremic-hypertensive syndrome with renal ischemia: an underrecognized disorder. 1020 41

To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a novel K+ channel opener, a single blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 28 healthy volunteers. The volunteers were randomly allocated to dosage groups of 50 micrograms, 100 micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were administered orally, after overnight fasting, and serial blood sampling and pharmacodynamic measurements were performed up to 48 hours after the drug was administered. The 200 micrograms group was further studied for food interactions in a crossover fashion. Drug concentrations in plasma were determined by HPLC. Hemodynamic changes after drug administration were evaluated by serial measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and total peripheral resistance (TPR), using computerized impedance cardiography. Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an active metabolite, showed linear pharmacokinetic characteristics, and food intake did not significantly affect the pharmacokinetic characteristics of either compound. Dose-related pharmacological effects were obvious for both the 200 micrograms and 300 micrograms groups. Hemodynamic parameters related to vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR, CI, and TPR, showed significant dose-dependent changes. The area under the time-effect curve (AUEC) of the parameters also showed a similar dose-dependent pattern. The PRA and PAC exhibited significant changes 4 hours after drug administration in the 300 micrograms group. Adverse effects, such as headaches, were more frequently observed at the higher dose levels. SKP-450 was generally well tolerated by these normotensive subjects. The antihypertensive efficacy of SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.
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PMID:Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers. 1088 17

Angiotensin II (AT-II)-receptor antagonists are reviewed. Research focused on blocking the renin-angiotensin system (RAS) led to the discovery of angiotensin-converting-enzyme (ACE) inhibitors, which are effective in the treatment of hypertension but are associated with a high frequency of cough and other adverse effects. AT-II-receptor antagonists were developed as agents that would more completely block the RAS and thus decrease the adverse effects seen with ACE inhibitors. AT-II-receptor antagonists include losartan, valsartan, irbesartan, candesartan, eprosartan, telmisartan, and tasosartan. Several clinical trials have demonstrated that AT-II-receptor antagonists are as effective as calcium-channel blockers, beta-blockers, and ACE inhibitors in the treatment of hypertension and induce fewer adverse effects. The adverse effects of AT-II-receptor antagonists--dizziness, headache, upper-respiratory-tract infection, cough, and gastrointestinal disturbances--occur at about the same rate as with placebo. [corrected]. All available AT-II-receptor antagonists seem to be equally effective in reducing both systolic and diastolic blood pressure, and they are comparable in cost. Currently, AT-II-receptor antagonists are used either as monotherapy in patients who cannot tolerate ACE inhibitors or in combination with other antihypertensive agents. Angiotensin II-receptor antagonists are well tolerated and are as effective as ACE inhibitors in decreasing blood pressure.
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PMID:Angiotensin II-receptor antagonists: an overview. 1090 66


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