Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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The effect of carmoxirole, a presynaptic dopamine (DA2) receptor agonist, on blood pressure, plasma catecholamines, renin-aldosterone and atrial natriuretic peptide and the intracellular concentration and transmembrane fluxes of Na+ and K+, in erythrocytes and platelets was studied in 24 normal men, using a double-blind, parallel study design. After a run-in period of 1 week, the subjects were treated with either placebo (n = 8) or 0.5 mg carmoxirole (n = 16) once daily for 1 week. Blood pressure and heart rate were not changed during carmoxirole administration in these normal men. Surprisingly, no significant effect of carmoxirole was found on the circulating plasma concentration of noradrenaline, adrenaline or dopamine. Other hormones such as renin, aldosterone and atrial natriuretic peptide were also not changed during carmoxirole administration. No significant effect of carmoxirole could be demonstrated on the intracellular concentration of Na+, K+, Mg2+ and Ca2+ and on the transmembrane fluxes of Na+ and K+ in erythrocytes and platelets. In the carmoxirole-treated subjects (n = 16), 6 subjects reported spontaneously adverse events such as syncope, dizziness and vomiting tendencies and/or fatigue.
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PMID:Erythrocyte and platelet cationic concentrations and transport systems in normal volunteers treated with carmoxirole. 790 90

The occurrence of severe sinus node dysfunction in 10 patients (three males and seven females; mean age 78.5 +/- 3.4, range 57-92 years) receiving oral diltiazem therapy (mean 190 +/- 20 mg/24 h, range 90-300) is described. Six of them were concomitantly taking amiodarone and/or beta-blocking agents. On admission, seven patients exhibited systemic hypotension and nine complained of asthenia and/or dizziness or drowsiness. ECG findings showed in all a persistent sinus arrest with atrial, junctional or ventricular escape, leading to a mean heart rate of 40.2 +/- 3 beats.min-1 (range 25-56). All patients had chronic renal failure on biological tests, with a mean endogenous creatinine clearance of 25 +/- 3 ml.min-1 (range 12-36). Intravenous calcium hydrochloride (mean 1.4 +/- 0.2 g, range 1-2), given in nine patients, rapidly restored stable sinus activity in seven. We suggest that diltiazem should be given cautiously to ageing patients with chronic renal failure, and confirm the efficacy of intravenous calcium in reversing calcium channel blocker toxicity on sinus node.
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PMID:Complete sinus arrest during diltiazem therapy; clinical correlates and efficacy of intravenous calcium. 801 8

The safety and tolerability of intermittent (16 hours on/8 hours off) nitrate patch therapy (0.2, 0.4 or 0.6 mg/hr: dose adjusted as required) was studied for a median duration of 356 days in 106 patients (mean age 60.9 +/- 8.6 years) with angina pectoris. Most patients (82%) were on existing beta-blocker and/or calcium antagonist therapy. Safety, tolerability and efficacy data were obtained by means of patient diary cards and regular clinic visits. Almost 90 treatment years revealed no significant or serious adverse events, and there were no changes in haematology or biochemistry associated with intermittent nitrate patch therapy. The most frequently reported side-effects were headache, skin reactions and dizziness (53%, 20% and 8% of patients respectively). Treatment resulted in a sustained reduction in the frequency and severity of angina attacks, reduced sublingual GTN consumption, an improvement in general wellbeing and a rise in the proportion of patients in whom angina was controlled.
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PMID:The long-term safety and tolerability of transdermal glyceryl trinitrate, when used with a patch-free interval in patients with stable angina. 826 Mar 32

We report the successful treatment of envenoming by the Gaboon viper (Bitis gabonica) and include results of in vitro investigations of the haemostatic properties of the whole venom. The patient was admitted to casualty soon after the bite with chest tightness, dizziness, nausea and swelling at the site of the bite and was treated immediately with polyspecific antivenom, hydrocortisone, chlorpheniramine and antibiotics. Results of haemostatic investigations were essentially normal on admission but on day 3 the thrombin time became prolonged and was associated with significant hypofibrinogenaemia and elevated D-dimers. Factors V and VIII, antithrombin III and protein C levels and platelet number were not significantly reduced. The haemostatic disturbances persisted for more than 24 h despite treatment with blood products (16 units of cryoprecipitate, 2 units of fresh frozen plasma and 6 units of platelet concentrate). Resolution of the abnormalities occurred only after administration of a further dose of antivenom. The period of hypofibrinogenaemia occurred at a time when venom antigen was undetectable in plasma by enzyme-linked immunosorbent assay. Studies in vitro with whole venom and a panel of amidolytic substrates commonly employed for measurement of haemostatic proteins revealed significant activity of venom with substrates sensitive to kallikrein and plasmin. The venom inhibited washed platelet aggregation induced by collagen, thrombin, arachidonic acid and the calcium ionophore A23187 in a dose-dependent manner.
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PMID:Accidental envenoming by a Gaboon viper (Bitis gabonica): the haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom. 846

The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
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PMID:Depo-Provera. 849 47

Levosimendan belongs to a new group of heart failure drugs, the calcium sensitizers. Because these compounds are not yet available for clinical use, the adverse drug events (ADEs) during levosimendan treatment cannot be predicted in detail. To evaluate the tolerability of levosimendan in human subjects, ADEs, safety laboratory values before and after treatment, and ambulatory ECG findings have been collected from several phase I and phase II clinical studies. By June 1994, approximately 200 subjects had received levosimendan. The most common ADE seen in healthy volunteers is headache, reported by some 40% of subjects in oral dosing but only 10% in i.v. dosing. The incidence of headache does not correlate well with the total daily dose of the drug. However, the controlled release formulations tested appear to cause vasodilatory symptoms more frequently than i.v. or rapid release oral formulations. The other typical vasodilatory ADEs seen in healthy volunteers are nausea, palpitation, and dizziness. Symptomatic hypotension is rarely encountered. It appears that heart failure patients tolerate the vasodilatory actions of the drug better than healthy volunteers. Only individual cases of headache, vertigo, and flushing have been reported, and injection site irritation has been the most commonly reported ADE (with an incidence <5%). However, because the longest administration of the i.v. infusion has been only 24 h, the duration of exposure to the drug is too short to allow any definitive conclusions to be drawn. All patients who have received levosimendan have been monitored with an ambulatory ECG. Even though some increase in heart rate is seen with high doses of the drug, there are thus far no signs of an increased incidence of ventricular tachyarrhythmias, nor have there been any noteworthy changes in the clinical laboratory safety tests. The experience with levosimendan is limited thus far and long-term data are lacking. It can be concluded, however, that at least in i.v. dosing the drug is devoid of ADEs with significant medical seriousness.
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PMID:Safety of levosimendan and other calcium sensitizers. 890 34

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

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

Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.
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PMID:Diversity and intensity of adverse events in the treatment of hypertension with barnidipine. 966 May 24

Forty-six patients were randomized to receive either 45 or 90-ml oral sodium phosphate (NaP) (Fleet Phospho-Soda), or X-Prep (a Senna preparation) before elective colonoscopy to compare the quality of colon cleansing, ease of preparation, and gastrointestinal intolerance. Before colonoscopy, one of us administered a questionnaire to the patient to assess how well the preparation was tolerated (scale from 1 to 5: 1 = easy, to 5 = unable to finish) and about the presence of four symptoms:abdominal pain, nausea, vomiting, and dizziness. The quality of colon cleansing was graded by two gastroenterologists (1 = excellent, 2 = good, 3 = fair, 4 = poor), who were unaware of how the patient was prepared or tolerated the preparation. The overall quality of bowel preparation with 90-ml oral NaP was better than with X-Prep and 45-ml NaP (p < 0.01). Patients found preparation with NaP to be easier than X-Prep (p < 0.002). No difference was seen in the incidence of abdominal pain, nausea, vomiting or dizziness. In the 90-ml NaP group, a significant rise in sodium and chloride occurred. However, increments were not greater than 5%. Hyperphosphatemia was noted with NaP, but was transient, and no concomitant decrease in calcium was seen. We conclude that, in the groups of patients studied, 90-ml NaP is a safe colonic cleansing agent that is better tolerated and more effective than others.
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PMID:A randomized prospective trial comparing 45 and 90-ml oral sodium phosphate with X-Prep in the preparation of patients for colonoscopy. 979 53


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