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Query: UMLS:C0018681 (headache)
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Nicorandil is a new vasodilator agent. Efficacy and safety of nicorandil in the treatment of angina pectoris have been evaluated through an extensive clinical program with a total of 1,680 patients who received the product. Results of hemodynamic studies provide clear evidence of the vasodilatory effect of nicorandil. In a population of patients with normal left ventricular function, a reduction in preload was apparent from a decrease in left ventricular end-diastolic pressure from 7.4 +/- 1.7 to -3.2 +/- 1.5 mm Hg. Furthermore, nicorandil produced marked reductions in total peripheral resistance (19%) and aortic blood pressures with decreases in systolic pressure of 34% and in diastolic pressure of 21%. At antianginal doses, nicorandil has a coronary vasodilating effect as well as a balanced peripheral action that leads to decreases in both preload and afterload. Therefore, nicorandil affects two of the main hemodynamic determinants of oxygen demand without impairing myocardial contractility or atrioventricular conduction. In addition, its strong spasmolytic activity is of particular interest when dynamic coronary obstruction is considered. Nicorandil clearly has demonstrated K(+)-channel-opening activity. In addition, the range of plasma concentrations in humans at therapeutic doses is similar to that of experimental models in which the K(+)-channel activity has been determined. This mechanism of action may explain the different hemodynamic profiles of nicorandil and nitrates in humans. Nicorandil is an effective and potent antianginal agent at a dose of 10-40 mg, which in monotherapy controls 69-80% of patients with stable chronic angina. Comparative trials have shown that the efficacy of nicorandil compares with that of drugs from the main classes of antianginal drugs--beta-blockers (atenolol, propranolol) and a Ca2+ antagonist (diltiazem). Patients treated for as long as 3 months or 1 year have shown sustained efficacy with no evidence of development of tolerance to the drug. The long duration of action allows effective treatment with a well-tolerated b.i.d. regimen. At the recommended doses, the main side effects were limited to headaches. They usually occurred early in the course of treatment and can be diminished by a progressive titration. From the large safety data base, there is no evidence that nicorandil induced exacerbation of myocardial ischemia or abrupt withdrawal syndrome. Nicorandil does not adversely affect the lipid profile or the glucose level. As an antianginal drug with a novel mechanism of action, nicorandil provides a useful alternative to existing antianginal agents in the long-term management of patients with angina pectoris.
J Cardiovasc Pharmacol 1992
PMID:Clinical profile of nicorandil: an overview of its hemodynamic properties and therapeutic efficacy. 128 84

In one multicenter, double-blind study, 659 hypertensive patients were treated for 16 weeks with either nilvadipine (n = 326) or nifedipine (n = 333). The major objective of the study was to compare the compatibility of the two calcium antagonists with regard to hepatic compatibility and side-effect profiles. The dosages were chosen so that the effective blood pressure reduction in both groups was equally good (mean decreases in systolic pressure of 27 +/- 12 mm Hg with nilvadipine and 26 +/- 15 mm Hg with nifedipine, and in diastolic pressure of 18 +/- 6 mm Hg with nilvadipine and 19 +/- 7 mm Hg with nifedipine). The mean heart rate was slightly lowered by about 2 beats/min by both substances. Although there was no effect on lipid or glucose levels, the serum glutamate-pyruvate transaminase (SPGT) levels were more often found to be raised in the nifedipine group than in the nilvadipine group (p < 0.05). The vasodilator effect of both calcium antagonists was responsible for side effects, of which the most common were flushing, edema, headache, and palpitations. The number of complaints was less in the group treated with nilvadipine than with nifedipine, especially flushing and edema. Significantly more patients in the nifedipine group withdrew from treatment due to undesirable side effects (p < 0.05).
J Cardiovasc Pharmacol 1992
PMID:The tolerability of nilvadipine compared to nifedipine in patients with essential hypertension. 128 91

Blood pressure and clinical status of 1,736 patients with cerebrovascular disease were observed during 12 months of treatment with nicardipine. The most common diagnoses were chronic cerebral ischemia (53.2%), transient ischemic attacks (TIA; 25.1%), and cerebral infarct (8.7%); 50.1% of patients were classed as hypertensive [systolic blood pressure (SBP) > or = 160 mm Hg or diastolic blood pressure (DBP) > or = 90 mm Hg]. Most patients (91.2%) received a daily dose of 60 mg nicardipine. Additional treatments included diuretics (37%), beta-blockers (11.5%), other antihypertensive drugs (15.8%), platelet antiaggregants (25.1%), and cardiotonic drugs (15.1%). A total of 282 patients (16.2%) were lost to follow-up, 21 (1.2%) patients withdrew due to side effects, 32 (1.8%) died, and 9 (0.5%) patients had treatment interrupted due to concomitant illness. In the hypertensive subgroup, blood pressure (SBP/DBP) was reduced from a mean baseline value of 175 +/- 22/97 +/- 14 mm Hg to 152 +/- 17/85 +/- 11 mm Hg at 3 months and 149 +/- 23/81 +/- 11 mm Hg after 12 months of treatment. The incidence of TIA or stroke among these patients was reduced from 29 cases (3.5%) during the first 3 months to 11 cases (1.54%) during months 4-12 (p < 0.01). In normotensive patients there were 18 (2.15%) cases during months 1-3 and 13 (1.55%) cases during months 4-12 (difference not significant). In the 280 patients treated with nicardipine alone, the most frequent side effects during the first month were facial flushing (6.8%), gastrointestinal problems (5%), dizziness (3.2%), headache (3.2%), drowsiness (3.2%), and hypotension (1.1%). Most of these side effects were transient.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990
PMID:The influence of nicardipine in patients with high risk of stroke. 136 3

At the end of a short-term (3-month) study of antihypertensive treatment of mild-to-moderate hypertension, 141 of the 200 study patients continued into a 2-year follow-up of isradipine as monotherapy or in combination with other antihypertensive agents. Although all 141 patients completed the first year, only 102 completed the study. Twenty-four patients dropped out: 2 with flushing; 1 each with arrhythmia, edema, angina, and headache; 12 who were noncompliant; 2 with disease unrelated to the study drug; and 4 for reasons unknown. Before the follow-up, 70% of the 141 patients were taking isradipine; after 2 years, 63% were still taking isradipine as monotherapy. During the follow-up study, the blood pressure remained stable (142.9/86.8 mm Hg after 3 months, and 142.9/86.2 mm Hg after 2 years), whereas the normalization rate was only slightly changed (73 vs. 75.2%). The incidence of reported adverse events decreased with time. At the end of the short-term study, 44.7% of patients had reported one or more adverse events; after 2 years of treatment, only 14.4% reported adverse events. Two patients had ECG signs of left ventricular hypertrophy: one showed no relevant changes while the other presented clear signs of regression. No clinically relevant laboratory abnormalities were noted during the study. In conclusion, isradipine is effective, well tolerated and safe in the long-term treatment of mild-to-moderate hypertension.
J Cardiovasc Pharmacol 1992
PMID:Long-term (2-year) isradipine data in the treatment of mild-to-moderate hypertension. 137 34

The clinical efficacy and tolerability of isradipine was evaluated in 63 patients with mild-to-moderate hypertension [supine systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) greater than or equal to 95 mm Hg]. Patients were divided into two groups according to age: group A (n = 41), aged 37-69 years (mean age of 54 +/- 7 years); group B (n = 22), aged 70-80 years (mean age of 72.8 +/- 2.4 years). After a 3-week washout period, group A received 2.5 mg of isradipine twice daily for 6 weeks. Group B received 1.25 mg of isradipine initially, increasing to 2.5 mg twice daily according to treatment response and tolerability. At the end of treatment (week 6), there were statistically significant decreases (p less than 0.01) in supine SBP and DBP in both groups compared with baseline values: the mean SBP in groups A and B decreased from 160.0 +/- 14.7 to 133.6 +/- 10.0 mm Hg and from 161.6 +/- 17.8 to 134.8 +/- 10.9 mm Hg, respectively; the mean DBP in groups A and B decreased from 101.3 +/- 3.0 to 83.6 +/- 5.5 mm Hg and from 101.3 +/- 8.4 to 84.2 +/- 3.6 mm Hg, respectively. Clinical and laboratory parameters did not change significantly during treatment. Side effects (headache, flushing, palpitations, and edema) were mild/moderate and disappeared after the first 2 weeks of treatment. In conclusion, 2.5 mg of isradipine twice daily is effective and well tolerated in the treatment of mild-to-moderate hypertension regardless of patient age.
J Cardiovasc Pharmacol 1992
PMID:Clinical efficacy and tolerability of isradipine in the treatment of mild-to-moderate hypertension in young and elderly patients. 137 36

Twenty-four patients with mild-to-moderate hypertension (19 women, 5 men; mean age of 49 +/- 9.1 years) completed a 2-week washout phase followed by 1 week of single-blind placebo. Patients were then given isradipine at 2.5 mg twice daily, which was increased to up to 7.5 mg twice daily according to the blood pressure response, over a 12-month period. Thirteen patients completed the trial. The supine and sitting blood pressure decreased to normal levels within 6 weeks of starting active treatment. Heart rate remained unchanged. Plasma cholesterol and triglycerides did not change significantly. Plasma high-density lipoprotein (HDL) cholesterol increased significantly (p less than 0.05) and a decrease (NS) was observed in low-density lipoprotein (LDL) cholesterol and in the LDL/HDL cholesterol ratio. Very-low-density lipoprotein (VLDL) cholesterol did not change, nor did other biochemical laboratory tests, or electrocardiographic and echocardiographic parameters. The most notable side effects were headache (n = 1), flushing (n = 1), palpitations (n = 3), and pretibial edema (n = 1). In conclusion, our results indicate that isradipine is safe and effective in the long-term treatment of mild-to-moderate hypertension. It also appears to have beneficial effects on lipid metabolism.
J Cardiovasc Pharmacol 1992
PMID:Metabolic, hematological, and cardiac effects of long-term isradipine treatment in mild-to-moderate essential hypertension. 137 37

In a double-blind, parallel-group comparative study, once-daily administration of a modified-release formulation of isradipine (Im, n = 189) was compared with twice-daily administration of the standard formulation (Is, n = 191). Following a 3- to 5-week placebo period, patients with a sitting diastolic blood pressure (sDBP) of greater than or equal to 100 mm Hg but less than or equal to 120 mm Hg were randomized to receive either Im at 5 mg once daily or Is at 2.5 mg twice daily for 6 weeks. A double-dummy technique was used to maintain blindness and no dosage titration was made. Blood pressure was always recorded in the morning before drug administration (12 h after the previous administration of Is or 24 h after the previous administration of Im). The mean sDBP was reduced significantly (p less than 0.001) and equally in both groups, and the normalization rate (sDBP less than or equal to 90 mm Hg) was 54% with Im and 55% with Is. Adverse events were slightly less frequent overall in the patients receiving Im than Is (23 vs. 28%, respectively) as was the incidence of typical dihydropyridine side effects such as flushing and headache. The results show that once-daily administration of 5 mg of Im is as effective and better tolerated than 2.5 mg twice daily of Is while providing adequate blood pressure control at the end of the 24-h dosing interval.
J Cardiovasc Pharmacol 1992
PMID:Clinical equivalence of once-daily administration of a modified-release formulation of isradipine and twice-daily administration of the standard formulation. Multicentre Study Group. 137 39

We studied the effects of nifedipine on blood pressure and on clinical and analytical parameters in hypertensive patients. Seven male and eight female subjects (mean age of 46.27 +/- 5.38 years, range of 41-56 years) with essential arterial hypertension were given nifedipine (20 mg b.i.d.) for 3 months. Before and after treatment, history, blood pressure, and biochemical values were recorded [blood: Na, K, Ca, creatinine, uric acid, triglycerides, cholesterol, HDL cholesterol, antidiuretic hormone (ADH), and aldosterone; urine: Na, K, Ca, creatinine, ADH, aldosterone, and percentage fraction of Na, K, and Ca excreted]. After 3 months of treatment, we found (a) significant decreases in systolic (147 +/- 18 vs. 166 +/- 16 mm Hg, p less than 0.001) and diastolic blood pressure (90 +/- 8 vs. 107 +/- 8 mm Hg, p less than 0.0007), triglycerides (107 +/- 47 vs. 120 +/- 49 mg/dl, p less than 0.0007), and cholesterol (236 +/- 4 vs. 257 +/- 44 mg/dl, p less than 0.00075) in blood, and in K excretion (50 +/- 19 vs. 46 +/- 19 mEq/g of creatinine, p less than 0.0007) and excreted fraction of K (49 +/- 6% vs. 8 +/- 5%, p less than 0.0012) in urine; (b) significant increases in HDL cholesterol (65 +/- 13 vs. 58 +/- 13 mg/dl, p less than 0.001) in blood, and in Na (115 +/- 73 vs. 109 +/- 69 mEq/g of creatinine, p less than 0.0007) in urine; and (c) no significant change in the remaining biochemical parameters, or in heart rate. Secondary effects included flushing (34%), headache (20%), ankle swelling (17%), dizziness (13%), palpitations (4%), and pruritus (4%).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992
PMID:Metabolic and antihypertensive effects of nifedipine in hypertensive patients. 137 8

The safety and tolerability of carvedilol, a new antihypertensive agent with the combined pharmacological activities of beta-blockade and vasodilation, and of nifedipine were investigated in patients with essential hypertension and non-insulin-dependent (type II) diabetes mellitus. Twenty patients were openly randomized to receive 25 mg carvedilol once daily (five men and five women; mean age, 63 years) or 10 mg nifedipine t.i.d. (three men and seven women; mean age, 64 years) for a period of 4 weeks. Baseline mean sitting blood pressures were 168/98 and 169/95 mm Hg in the carvedilol and nifedipine groups, respectively. Baseline mean areas under the curve (AUC) of the intravenous glucose tolerance test (IVGTT) for the carvedilol and nifedipine groups were 6,136 +/- 1,195 and 6,287 +/- 1,228 mg/dl/min, respectively. Demographic and efficacy variables were not statistically different between treatment groups. After 4 weeks of therapy, mean sitting blood pressure was significantly (p less than 0.02) reduced to 144/91 mm Hg in the carvedilol group and to 149/87 mm Hg in the nifedipine group. Week 4 IVGTT AUC values of 5,735 +/- 1,464 mg/dl/min in the carvedilol group and 5,988 +/- 993 mg/dl/min in the nifedipine group, representing mean reductions of 6.14% and 3.17%, respectively, were not statistically different from baseline. Both treatments were well tolerated. No patient experienced adverse events in the carvedilol treatment group, whereas two patients in the nifedipine group reported episodes of headache (one patient) and palpitations (one patient); each episode was mild in severity and considered to be related to study medication.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992
PMID:Comparison of the effects of carvedilol and nifedipine in patients with essential hypertension and non-insulin-dependent diabetes mellitus. 137 56

The quality of life (QL) was evaluated in a 6 month double-blind trial in six European countries. Patients with a sustained supine diastolic blood pressure (SDBP), phase V, of 95 mm Hg or more on bendrofluazide, 5 mg daily (or an equivalent dose of a thiazide diuretic) were randomised to additional pinacidil (n = 127), 25 mg up to 100 mg daily, or nifedipine (n = 130), 20 mg up to 80 mg daily. The treatment groups were similar at entry for QL scores, average DBP of 103 +/- 6 (SD) mm Hg, and average age of 56 +/- 10 (SD) years. Eighteen patients on pinacidil and 12 on nifedipine withdrew due to side effects, such as oedema (both drugs) and flushing (nifedipine). The maximum antihypertensive effect was achieved within 6 weeks and maintained, resulting in a significant fall in SDBP of 13.7 mm Hg on pinacidil and 15.5 mm Hg on nifedipine at the end of the trial. There was no significant difference in the antihypertensive effect. The target SDBP was achieved in 57% of pinacidil-and 63% of nifedipine-treated patients. The average number of symptomatic complaints fell in both groups, with significant decreases in the reporting of blurred vision and headaches on nifedipine. Complaints of growth of body and facial hair increased on pinacidil but there were no significant between-drug comparisons with respect to side effects. In measures of psychological well being, patients on pinacidil showed a significant (p less than 0.05) improvement in total and cognitive function scores compared to nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992 Jul
PMID:Quality of life on antihypertensive therapy: a double-blind trial comparing quality of life on pinacidil and nifedipine in combination with a thiazide diuretic. European Pinacidil Study Group. 138 18


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