Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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We report the case of a 42-year-old female, affected by mitral valve prolapse and ventricular arrhythmias, who died suddenly from ventricular fibrillation recorded during Holter monitoring. The lethal arrhythmia initiated with late diastolic couplets followed by a ventricular tachycardia that eventually degenerated into ventricular fibrillation. The patient had experienced four orthostatic and stress-related syncopal episodes, associated with nausea and diaphoresis, and a positive tilt test. Holter monitoring documented ventricular arrhythmias, consisting of both isolated monomorphic and sporadic repetitive beats. Her standard ECG and exercise test were normal, but signal-averaged study findings were significantly positive. QT prolongation in the absence of arrhythmias was observed during the Valsalva manoeuvre and isoproterenol infusion. 2D echo showed a remarkable mitral valve prolapse without regurgitation and localized structural abnormalities of the right ventricle. Postmortem study confirmed mitral valve prolapse, and also disclosed pulmonary infundibulum dilatation, massive adipose infiltration of the right ventricular free wall, patchy fibrosis and scattered myocardial inflammatory infiltrates in the left ventricle; these features are all consistent with arrhythmogenic right ventricular cardiomyopathy.
Int J Cardiol 1995 May
PMID:Sudden death in mitral valve prolapse with Holter monitoring-documented ventricular fibrillation: evidence of coexisting arrhythmogenic right ventricular cardiomyopathy. 764 75

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.
Am J Cardiol 1995 Jun 01
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

Hundred and twenty-three outpatients were treated with oral cibenzoline for 3 months in order to test the efficacy and safety of the compound in the prevention of the recurrence of supraventricular arrhythmias. The dose was 260-390 mg/day for those under 70 and 130-260 mg/day for those over 70 years. All patients were converted to sinus rhythm before entry to the study and 95 patients had previously been treated with one or more drugs which had been discontinued due to lack of effect and/or poor tolerability. In 21 patients (17%) recurrence was documented by ECG or Holter monitoring, cibenzoline thus being effective in 83%. In 35 other patients there was a return of symptoms but no confirmation of recurrence. There were no relevant changes in blood pressure or heart rate. PR, QT and QTc intervals were stable but mean QRS interval increased slightly during the first week before stabilizing. Cibenzoline was discontinued because of adverse events in only 10 patients (8.1%). The most frequent complaints were nausea, vertigo and faintness. Seventy-two per cent of patients rated their well-being as "well/very well" at month one compared with 84% at month three. Cibenzoline is an appropriate first line choice in this indication.
Acta Cardiol 1995
PMID:Cibenzoline in the prevention of recurrence of supraventricular arrhythmias. 777 Nov 75

The diagnostic accuracy, safety and tolerance of adenosine thallium scintigraphy have been reported using a 2-site intravenous infusion with either a titrated or fixed-dose protocol. A single-site infusion would considerably simplify the test procedure, but its safety must be established before it can be recommended. Accordingly, 400 consecutive patients who had adenosine and thallium-201 administered through the same intravenous line were classified into 2 groups. Group I (n = 201) patients received a 7-minute titrated intravenous infusion of adenosine, with an initial dose of 50 micrograms/kg/min that increased at 1-minute intervals to a maximum of 140 micrograms/kg/min. Group II (n = 199) patients received a fixed dose of adenosine at 140 micrograms/kg/min for 6 minutes. Adenosine significantly (p < 0.001) increased heart rate and decreased systolic blood pressure by similar amounts in both groups. Adverse effects occurred more often (88 vs 71%, p < 0.001) and started earlier (2.8 vs 3.6 minutes, p < 0.001) in group II. There was no significant difference in the occurrence of second- and third-degree atrioventricular block between the 2 groups (4.0 vs 5.0%); however, chest pain, flushing and nausea were all more frequent in group II. Severe side effects were seldom seen in either group and occurred in 9 group I and 8 group II patients. Scintigraphic findings were similar in both groups. Transient perfusion defects were seen more often in patients with than without second- or third-degree atrioventricular block (42 vs 21%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Cardiol 1994 Jan 15
PMID:Safety of single-site adenosine thallium-201 scintigraphy. 829 44

Prostacyclin (PGI2) is a bioactive substance produced by vascular endothelial cells, which exerts powerful vasodilative and anti-platelet actions. Patients with pulmonary hypertension have an imbalance between vasodilative PGI2 and vasoconstrictive thromboxane B2 (TXB2). Treatment with vasodilative agents is essential for such patients. Continuous intravenous infusion of PGI2 is an effective treatment of primary pulmonary hypertension in terms of exercise capacity and survival rate. We tested a new stable PGI2 analogue, beraprost sodium (Procyclin, Dornar) suitable for oral administration, in patients with primary and secondary pulmonary hypertension. A short-term study of cardiac catheterization in four patients with primary pulmonary hypertension showed a 15 +/- 12% reduction in mean pulmonary artery pressure in three of the four patients, and a 24 +/- 22% decrease in pulmonary vascular resistance in all four patients. Cardiac index increased by 27 +/- 14% in three of the four patients. Among three patients with secondary pulmonary hypertension, there was a 7% reduction in pulmonary artery pressure in one patient, and a 24 +/- 14% decrease in pulmonary vascular resistance in all three patients. In a long-term study (23 +/- 11 months), NYHA functional class improved from 3.0 +/- 0.7 to 2.4 +/- 0.5 in two of the five patients with primary pulmonary hypertension. Although the radiographic cardiothoracic ratio was not significantly improved, cardiac index increased by 78 +/- 60% in four of the five patients. Only two patients, one with primary and one with secondary pulmonary hypertension, died during the long-term follow-up period. Plasma TXB2/6-keto prostaglandin F1 alpha ratio decreased from 8.1 +/- 8.7 to 1.5 +/- 0.4. The optimal dose remains uncertain, but the initial dosage of 40-60 micrograms/day given in three to four doses for adult patients is considered to be acceptable. Side effects such as flushing face, headache, vomiting, and nausea were mild and resolved when the dose was reduced. Oral PGI2, beraprost, appears to be an effective and possibly adequate substitute for intravenous vasodilators in pulmonary hypertension for both short- and long-term management.
J Cardiol 1996 Apr
PMID:[Short- and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension]. 864 6

To evaluate the safety of intravenous dipyridamole thallium-201 imaging as an alternative to exercise thallium imaging in the evaluation of coronary artery disease, clinical data from 140 patients were retrospectively analyzed. Adverse effects were experienced by 39 patients (27.9%) with a total number of 52 effects: chest pain (23), dizziness (13), headache (7), nausea (7), dyspnea (2). All patients presented complete relief of symptoms. In 15 patients administration of aminophylline was necessary. Major effects (fatal and non fatal myocardial infarction and acute bronchospasm) were not registered. Vital sign data change observed after infusion of dipyridamole was: decreased blood pressure and increased pulse rate. Patient's age and incidence of coronary artery disease did not differ significantly in the subgroup of patients with adverse effects versus the group of patients without it.
Rev Port Cardiol 1996 Feb
PMID:[Pharmacological stimulation with dipyridamole in thallium-201 myocardial perfusion scintigraphy: a study of the secondary effects]. 864 76

The efficacy and safety of trandolapril alone and in combination with a calcium channel blocker were evaluated in 13,147 hypertensive patients over 60 years old. Two patient groups were constituted. After a 2-week wash-out period, the patients in group I received monotherapy with trandolapril 2 mg/day for 4 weeks. Trandolapril was continued for another 4 weeks in responding patient, otherwise the dosage of trandolapril was doubled or another antihypertensive was added. Group 2, composed of patients previously treated with a calcium channel blocker with insufficient efficacy, was treated according to the same treatment regimen, but the calcium channel blocker was maintained throughout the study. 13,147 patients (group 1: 11,329 patients, group 2: 1,818 patients) with a mean age of 68 +/- 7 years were followed. After 4 weeks of treatment, the blood pressure measured by mercury sphygmomanometer decreased from 176 + 11/99 +/- 8 mmHg to 164 +/- 12/87 +/- 7 mmHg (p < 0.0001). This blood pressure fall was similar in group 1 (-22 +/- 12/-12 +/- 8 mmHg) and in group 2 (-21 +/- 11/-12 +/- 8 mmHg). In the pure systolic HT subgroup treated by trandolapril monotherapy, the antihypertensive effect predominantly affected the SBP (-23 +/- 12/- 4 +/- 6 mmHg). The antihypertensive effect was correlated with the initial blood pressure. In group 1, in the case of insufficient response to trandolapril monotherapy, the addition of a calcium channel blocker was the strategy which achieved the most marked antihypertensive effect (ANOVA, p < 0.0001). This bitherapy was more effective than the trandolapril+diuretic combination (-18 +/- 11/- 11 +/- 8 mmHg and -15 +/- 10/- 9 +/- 7 mmHg, respectively (p < 0.001). A total of 1,270 adverse events were reported by 996 patients (7.6%), leading to discontinuation of treatment in 372 patients (2.8%). The most frequent adverse effects were cough (2.8%), headache (0.8%), vertigo (0.8%) and nausea (0.5%). Only one minor equivalent of angioneurotic oedema was reported. In conclusion, trandolapril is effective and well tolerated in elderly hypertensive patients. In the case of pure systolic HTA, its action is essentially exerted on SBP. The combination of trandolapril+calcium channel blocker appears to be the most effective strategy in the case of incomplete blood pressure control by trandolapril alone.
Ann Cardiol Angeiol (Paris) 1995 Nov
PMID:[Evaluation of trandolapril alone or in combination with a calcium channel blocker in hypertensive patients over 60 years of age]. 874 62

Arrhythmias are common after cardiac surgery and are associated with hemodynamic compromise, stroke, and prolonged hospitalization. Beta blockers prevent atrial fibrillation postoperatively, but there are few data regarding the prophylactic use of type 1 antiarrhythmic agents or the prevention of ventricular arrhythmias. Accordingly, we performed a randomized, double-blind, placebo-controlled study of the effects of oral procainamide on 100 patients undergoing elective coronary artery bypass surgery. Procainamide was received for 4 days; the dosage was adjusted for body weight. Patients receiving procainamide had a significant reduction in atrial fibrillation (16 vs 29 patient-days, p < 0.05) and ventricular tachycardia (2% vs 20%, p < 0.01). However, the incidence of atrial fibrillation was not significantly reduced (38% vas 26%). In the group achieving therapeutic serum procainamide levels, there was reduction in all measured postoperative arrhythmias. No serious cardiac or noncardiac adverse events were noted during procainamide therapy, although there was a significant increase in the incidence of nausea. We conclude that procainamide reduces arrhythmias in the early postoperative period after coronary artery bypass surgery, most prominently in patients who achieve therapeutic serum levels. This was associated with no serious cardiac adverse reactions.
Am J Cardiol 1996 Nov 01
PMID:Efficacy and safety of procainamide in preventing arrhythmias after coronary artery bypass surgery. 891 73

An 81-year-old woman reported with chest pain occurring shortly after initiating treatment with sertraline. She had no prior history of cardiovascular disease. She developed nausea and malaise 4 h after her first dose, which resulted in avoidance of further treatment. After voluntarily reinitiating sertraline 10 days later, she again developed nausea and malaise but persisted with treatment. On the second day, her gastrointestinal symptoms were accompanied by crushing retrosternal chest pain radiating to both arms and resolving spontaneously after 10 mins. Following the third dose of sertraline, the patient experienced severe and persistent crushing retrosternal chest pain radiating to both arms. She was hospitalized with a diagnosis of unstable angina and treated with acetylsalicylic acid, intravenous heparin and nitroglycerin. The temporal relationship of chest pain onset following ingestion of sertraline is strongly suggestive of an adverse medication effect.
Can J Cardiol 1997 Sep
PMID:Unstable angina associated with sertraline. 934 35

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
Am J Cardiol 1999 Mar 04
PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39


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