Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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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

A prospective study was performed of the correlation of ventricular late potentials (LP) and clinical parameters in patients after acute myocardial infarction. To evaluate the prognostic significance of the signal-averaged-electrocardiogram (SAECG) in risk stratification of sudden cardiac death and arrhythmogenic events, the clinical characteristics of these post-infarction patients were performed in a follow-up-period. 243 consecutive patients underwent SAECG for detection of late potentials in the second week after acute myocardial infarction. After a mean follow-up of 9 months the patients were asked a standardized questionnaire. Late potentials are independent of age, sex, left ventricular ejection fraction, peak activity of MB fraction of creatine kinase, and the cardiovascular risk factors in postinfarction patients. In patients, who received thrombolytic therapy, the incidence of late potentials is lower (p < 0.05) and in patients with posterior wall infarction it is significantly higher (p < 0.04). In the follow-up period patients with abnormal SAECG show a significantly higher rate of angina pectoris, palpitations, dizziness, and syncope. By way of contrast, postinfarction patients with normal SAECG feel mainly comfortable in the follow-up (p < 0.01). The mortality was even in both groups. Sudden cardiac death in the late postinfarction period shows a significant correlation with the finding of late potentials in SAECG in the early myocardial infarction period (p < 0.01). The SAECG for detection of late potentials as a non-invasive investigation in the early postinfarction period characterizes patients with an arrhythmogenic risk, especially sudden cardiac death, independent of other conventional methods. Furthermore, the impaired patient with clinical symptoms in the late postinfarction period is hereby identified.
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PMID:[Late potentials in the diagnosis of post-infarction patients: arrhythmogenic risk and clinical symptomatology]. 948 May 81

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

A centre for trans-telephonic electrocardiographic monitoring (TTEM) was established at the Escorts Heart Institute in May 1996. We have reviewed our experience in the first 398 patients. There were 321 males (81%) and 77 females (19%); their age range was 1 month to 95 years. Sixty-five per cent of patients were from New Delhi, while the remainder were from other cities in India and abroad. As well as follow-up of patients after discharge, the system was used for the evaluation of chest pain, palpitation, chronic angina, arrhythmias, and pacemaker implants. Out of 664 symptomatic transmissions, 510 (77%) were for cardiac symptoms like chest pain (309), palpitation (90), uneasiness (61), dizziness (28) and breathlessness (22); the other 154 (23) were for non-cardiac symptoms like stitch pain and backache (51), typical chest pain (39), weakness and fever (45), and sweating (19). The majority of patients with chest pain (84%), palpitation (78%) and dizziness (75%) transmitted their electrocardiograms within one hour of the onset of the symptoms. Out of 664 symptomatic transmissions, 531 required either reassurance or drug-dose adjustment by telephone and 97 were called to the outpatient department on an elective basis. Immediate hospitalization was advised for 36 patients, for acute management of their symptoms. TTEM was useful in avoiding 628 unnecessary visits to the hospital, while 36 patients were immediately hospitalized for acute care.
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PMID:Trans-telephonic electrocardiographic monitoring--experience in India. 964 Jul 18

Pacemaker syndrome is caused primarily by the lack of atrial kick and by neurocardiogenic reflex mechanisms due to simultaneous atrial and ventricular contractions. The most common clinical symptoms are dyspnoe, hypotension, dizziness and syncopal attacks. A case report of a patient with pacemaker syndrome is presented, in which the main clinical manifestation was a recurrent chest pain. A VVI demand pacemaker was implanted because of sick sinus syndrome ten years ago and shortly afterwards anginal attacks of rest developed. Coronary angiography revealed a non-significant (25%) narrowing of the right coronary artery (RCA). Casual and long-term ambulatory blood pressure (ABPM) measurements elucidated that the patient occasionally has extremely low diastolic blood pressure. This later phenomenon was confirmed and refined by a "beat-to-beat" blood pressure measuring technique. The elimination of the pronounced "beat-to-beat" variability of arterial blood pressure and transient coronary hypoperfusion due to implantation of an AV sequential bifocal pacemaker resulted in a full disappearance of angina pectoris.
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PMID:[Angina pectoris induced by pacemaker syndrome]. 964 55

In this study, insomnia in 80-year-olds was related to medical, psychological and social factors. The data were based on examinations every year in people aged between 80 and 89 years. Of 333 people living in the city of Lund and born in 1908, 67% participated. Increased severity of insomnia was significantly associated with use of diuretics, other cardiovascular drugs, hypnotics and laxatives, and with nervousness, difficulty relaxing, anorexia, nausea, constipation, backache, feeling cold, sweating, loss of weight, dizziness, depression, general fatigue, exhaustion, angina pectoris, cardiac insufficiency, worsened objective and subjective health, presence of negative T-waves on ECG, anxiety, total life satisfaction, neuroticism, disbelief in a just world, feeling lonely and lower survival rates. Thus insomnia has widespread associations with different aspects of life in 80-year-olds.
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PMID:Insomnia in an 80-year-old population: relationship to medical, psychological and social factors. 978 73

The slow progression of valvular aortic stenosis enables the left ventricular myocardium to adapt itself to the increasing afterload. When myocardial adaption is exhausted, surgical intervention is urgent, the prognosis, however, is already limited. To quantify the hemodynamic severity of aortic stenosis, transaortic pressure gradients (dp) measured by Doppler echocardiography or hemodynamically are inappropriate, because dp is significantly dependent on the transaortic flow volume. In severe aortic stenosis, despite constant narrowing of the aortic valve area, the reduced stroke volume results in decreasing transaortic pressure gradients. With aortic valve resistance or transaortic pressure loss (PL)--the quotient of pressure gradient and stroke volume--the hemodynamic severity of aortic stenosis can be described accurately. If PL is known, a decompensated aortic stenosis (PL > 1 mm Hg/ml) may be differentiated from myocardial failure of another etiology and a concomitant left ventricular outflow tract obstruction. With respect to medical therapy, the prevention of bacterial endocarditis and thromboembolic complications is important. Knowing the potential danger of syncopies and ventricular arrhythmias during exercise with increasing severity of aortic stenosis, patients have to be informed about their limited functional capacity. The occurrence of typical symptoms during the natural history of chronic aortic stenosis (e.g. dizziness, syncopes, angina pectoris, arrhythmias) manifestation of ST-T-alterations or silent myocardial ischemias and demonstration of an inadequate myocardial adaptation to the chronic pressure overload in asymptomatic patients are accepted indications for a surgical intervention. If the indication for surgery remains uncertain, stress tests (e.g. radionuclidventriculography) may be performed to demonstrate an exhausted myocardial adaptation. If the PL and the severity of aortic valve/anulus calcification is known, the progression of a chronic aortic stenosis can be estimated. This might be important, if a cardiosurgical intervention has to be performed for other indications and aortic stenosis is co-existent but does not require an intervention at that time. For prognostic reasons myocardial decompensation due to aortic stenosis is an indication for an urgent surgical intervention. Attempts for medical recompensation or bridging strategies (e.g. balloon valvotomy) worsens the prognosis significantly.
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PMID:[Diagnostic approach and optimal treatment of aortic valve stenosis]. 985 38

Advanced controlled release (CR) dosage forms are relative newcomers to pharmaceutical markets, and few studies relate their efficacy, safety or compliance benefits to economic value. This literature review was undertaken to assess the cost effectiveness of CR dosage forms using such measures as purchase costs, total treatment costs, and economic value of improved therapeutic outcomes compared with those with non-CR dosage forms. Three therapeutic areas were examined: cardiovascular therapy, pain management and estrogen replacement therapy. In cardiovascular therapy, prescription costs of sustained release (SR) verapamil were significantly higher than for conventional release verapamil. However, these were more than offset by lower physician, hospital and laboratory expenditures for the SR group, in whom compliance was superior. Similarly, patients receiving SR diltiazem had better prescription refill compliance than those using a conventional formulation of the drug, as well as significantly lower aggregate healthcare costs during a 1-year study period. These lower costs with both SR verapamil and diltiazem may relate to better compliance. CR nifedipine has lower daily acquisition costs than the conventional form, simplifies the dosage regimen to once daily, extends the indications of the drug to hypertension as well as angina, and reduces vasodilatory adverse effects by reducing peak plasma drug concentrations and the postdose rate of increase in concentration. Compared with oral clonidine given twice daily, transdermal clonidine, given once weekly, had higher purchase costs, but was associated with improved compliance, reduced adverse effects (due to control of plasma concentrations), and lower nondrug health costs, such as physician, hospital and laboratory costs. Lower costs were also found for once daily oral formulations of various antihypertensives, suggesting that the economics of both types of CR dosage forms related to compliance. CR metoprolol 50 or 100mg and conventional release atenolol 50mg, each given once daily, provided effective beta1-adrenoceptor blockade. The conventional formulation caused deterioration in the sense of well-being that was temporally associated with sharp peaking of its plasma concentrations. Such peaking did not occur with either dose of CR metoprolol, nor did any deterioration in the sense of well-being. Transdermal nitroglycerin (glyceryl trinitrate), compared with long-acting oral nitrates, improved quality of life (QOL) {despite a higher incidence of some adverse effects, such as headache, dizziness and skin irritation}. Furthermore, in some studies, this formulation reduced angina attacks, sublingual nitroglycerin use, and hospitalisation or emergency room use. Cost comparisons between transdermal products favoured those that have superior adhesion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Translating safety, efficacy and compliance into economic value for controlled release dosage forms. 1015 Jan 60

Trans-Telephonic Electro-Cardiographic Monitoring (TTEM) centre, is an easy to use tool, now freely available in India. Between May 1996 and May 1997, 398 patients were registered at Escorts Heart Alert Centre (EHAC) for TTEM; 321 (81%) males and 77(19%) females. Age range was from 1 month to 95 years 65% patients were from New Delhi; 35% from other cities in India and abroad. Patients' clinical profile were post-CABG, post-PTCA, post-MI, patients after discharge; evaluation of chest pain, palpitation, chronic angina, arrhythmias, and pace-maker follow up. Out of 664 symptomatic transmissions, 510 (77%) were for cardiac symptoms like chest pain 309 (61%); palpitation 90 (18%); uneasiness 61(12%); dizziness 28(5%) breathlessness 22(4%). 154(23%) were for non-cardiac symptoms like stitch pain and backache (51); Atypical chest pain (39); weakness and fever (45) and sweating (19). 84%, 78% and 75% patients of chest pain, palpitation and dizziness respectively transmitted their ECGs within one hour of the onset of the symptoms. Out of 664 symptomatic transmissions, 531 required either re-assurance or drug-dose adjustment on telephone. 97 were called to OPD on elective basis. 36 patients were advised immediate hospitalization, for acute management. TTEM was useful in avoiding 628 unnecessary visits to the hospital whereas 36 patients, were immediately hospitalized, for receiving acute life-saving interventions.
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PMID:Trans-telephonic electro-cardiographic monitoring (TTEM)--first Indian experience. 1018 May 71

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.
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PMID:Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN). 1037 20


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