Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mibefradil (Ro 40-5967) is a novel calcium antagonist from a new chemical class and is the first that selectively blocks the T-type calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations > 300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type calcium-channel selectivity.
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PMID:Effects of the new calcium antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: a multicenter, placebo-controlled study. Ro 40-5967 International Study Group. 757 82

The results of an open prospective study that evaluated the long-term clinical safety of nicorandil are presented. This study included 199 patients with severe chronic stable angina treated over a 1-year period. The most often reported adverse event was headache, which was responsible for most of the study withdrawals due to clinical intolerance (9.6%). When using a progressive titration scheme, this incidence was substantially reduced to 2.7%. As with other less frequent adverse events (dizziness, gastrointestinal disorders), headaches were reported as being mild to moderate in severity, were experienced during the first days of treatment, and, if treatment was maintained, usually resolved within a few days. The incidence of adverse events was not modified when nicorandil was given in combination with a beta-blocker, a calcium antagonist, or both agents. Cardiovascular safety was satisfactory and laboratory parameters were not altered. At the end of the study, 70% of patients were maintained on nicorandil. These results are in agreement with those reported from the nicorandil safety database, which gathered 1152 patients treated by nicorandil, including those of the present study. In comparative studies of nicorandil versus beta-blockers, calcium antagonists, or nitrates, the overall incidence of adverse events was no different between the two treatment groups, although the safety profile differed according to the drug category.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nicorandil safety in the long-term treatment of coronary heart disease. 764 28

This double-blind, placebo-controlled, parallel-group, multicenter study was designed to evaluate the safety and efficacy of a new controlled-onset, extended-release formulation of verapamil hydrochloride called physiologic pattern release (PPR) verapamil. The study was conducted at 24 sites (13 United States, 5 Canada, 6 overseas; see Appendix). Following a 1- to 3-week single-blind placebo lead-in period, 278 patients with chronic stable angina pectoris (247 males, 31 females, mean age 60.8 years, range 32 to 78) were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: verapamil 180, 360, or 540 mg, or placebo. PPR verapamil at all doses significantly increased (p < 0.05) time to moderate angina and symptom-limited exercise duration, and verapamil 360 mg significantly increased (p < 0.05) time to > or = 1 mm ST-segment depression, after 4 weeks of treatment when assessed 24 hour after the previous dose. Larger doses of verapamil were associated with proportionately greater improvements in exercise tolerance. Frequency of anginal attacks was also reduced by verapamil. The most frequently observed adverse events were dizziness, headache, constipation, and nausea. The incidence of constipation was high (20.9%) within the 540 mg treatment group. This verapamil formulation can be clinically titrated within a 180 to 540 mg dosing range, permitting effective once-daily administration for the treatment of chronic stable angina.
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PMID:Placebo-controlled evaluation of three doses of a controlled-onset, extended-release formulation of verapamil in the treatment of stable angina pectoris. 776 93

This study assessed the safety, tolerability, and efficacy of mibefradil when added to beta-blocker monotherapy in patients with chronic stable angina pectoris. Two hundred five patients were randomized to receive double-blind treatment with either placebo (n = 70), mibefradil 25 mg (n = 67), or mibefradil 50 mg (n = 68) for 2 weeks. Exercise tolerance tests (ETTs) were performed at the end of the run-in (baseline) and double-blind treatment periods, and patients maintained an anginal diary. Compared with placebo, treatment with mibefradil 50 mg resulted in significant increases in exercise duration (36 +/- 51 seconds; p = 0.036), time to onset of angina (48 +/- 65 seconds; p = 0.002), and time to persistent 1-mm ST-segment depression (47 +/- 77 seconds; p = 0.004). Greater reductions in heart rate, blood pressure, and the rate-pressure product were more apparent at each stage of the ETT in the 50-mg mibefradil group than in the placebo group. Daily treatment with mibefradil 50 mg was associated with a significant decrease in the number of weekly anginal attacks (-2.1 +/- 4.0, p = 0.020) compared with placebo. The addition of mibefradil to existing beta-blocker therapy was well tolerated. Dizziness was the most frequently reported adverse event in the mibefradil 50-mg dose, and occurred with an incidence of 4.4%. The addition of mibefradil 50 mg, administered once daily, to patients on stable beta-blocker therapy produced additive antianginal and anti-ischemic effects and was well tolerated.
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PMID:Additional antianginal and anti-ischemic efficacy of mibefradil in patients pretreated with a beta blocker for chronic stable angina pectoris. 911 58

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

Between May 1996 and May 1997, a total of 398 patients (321 males, 77 females) were registered at our institute for trans-telephonic electro-cardiographic monitoring (TTEM). Their age ranged from one month to 95 years. Almost two-third (67%) of patients were from Delhi and one-third (33%) from other places in India and neighbouring countries. Clinical profile of these patients was post-bypass surgery, post-myocardial infarction, chest pain for evaluation, post-percutaneous transluminal coronary angioplasty, chronic stable angina, evaluation of palpitations, arrhythmias, and pace-maker follow-up. Out of 664 symptomatic transmissions, 568 (86%) were received for cardiac symptoms and 96 (14%) for non-cardiac symptoms. Seventy-nine percent patients had chest pain or palpitations at the time of transmission, whereas 21 percent had other symptoms like chest discomfort, breathlessness or dizziness. The electro-cardiograms were transmitted within one hour of the onset of chest pain in 84 percent, palpitations in 78 percent and dizziness in 75 percent. Of patients with symptomatic transmissions, 628 (95%) required either reassurance or drug-dose adjustment and outpatient department review. Only 36 (5%) patients were hospitalised as an emergency, and out of these only 19 (3%) needed acute management. In conclusion, trans-telephonic electro-cardiographic monitoring is a very convenient and an 'all-time-available' monitoring facility for establishing patient-physician contact in the shortest time. It is useful in rendering instant advice for hospitalisation in emergency situations while avoiding unnecessary visits to the hospital.
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PMID:Evaluation of cardiac symptoms by trans-telephonic electro-cardiographic monitoring (TTEM): preliminary experience. 958 88

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

(1) Ranolazine-- an adjunctive treatment to beta-blockers, calcium channel blockers, or long-acting nitrates-- is indicated for patients with chronic stable angina who have not responded to standard anti-anginal therapy. (2) In three randomized controlled trials (RCTs), ranolazine, in combination with standard anti-anginal medications, led to modest but statistically significant improvements in exercise duration, and reductions in the frequency of angina episodes and nitroglycerin consumption, when compared to standard anti-anginal medications only. The clinical significance of these improvements is unknown. Most of the participants in studies were male and Caucasian. Thus, there are questions about the drug's efficacy in other populations. (3) One RCT suggests that the addition of ranolazine to standard treatment is ineffective in reducing major cardiovascular events that are associated with acute coronary syndromes. (4) The adverse effects reported with ranolazine include dizziness, nausea, asthenia (weakness), constipation, and headache. Long-term data from one trial indicate that there is no significant increase in the incidence of death or arrhythmia among those taking ranolazine. More clinical trials of ranolazine are needed to confirm its long-term safety, its optimal dosing, its efficacy in combination with full dose beta-blockers with or without calcium channel blockers, and its potential role in the treatment of other cardiovascular conditions.
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PMID:Ranolazine (Ranexa) for chronic stable angina. 1759 50

Ranolazine is a new and unique antianginal drug that has been approved for the treatment of chronic stable angina pectoris. The drug is administered as a sustained-release formulation. Although the drug's mechanism of action has not been fully elucidated, current thinking is that ranolazine, a selective inhibitor of late sodium influx, attenuates the abnormalities of ventricular repolarisation and contractility associated with ischaemia. Three randomised trials have shown efficacy for ranolazine in increasing exercise testing or reducing anginal episodes or use of glyceryl trinitrate. Side-effects include dizziness, constipation, nausea, and the potential for prolongation of the QT(c) interval. Ranolazine seems to be a safe addition to current traditional drugs for chronic stable angina, especially in aggressive multidrug regimens.
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PMID:Ranolazine for chronic stable angina. 1892 5

Beta-blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta-blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta-blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta-blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta-blockers increase all-cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta-blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta-blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta-blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta-blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta-blockers but attest to their usefulness for specific cardiovascular indications.
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PMID:Cardioprotection with beta-blockers: myths, facts and Pascal's wager. 1970 92


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