RESUMEN
OBJECTIVE: To evaluate the responsiveness of joint counts, patient-reported measures and proposed composite scores in hand osteoarthritis (HOA). METHODS: Data were used from a previously reported study in which 83 patients with HOA were randomly assigned to CRx-102 or placebo. CRx-102 consists of prednisolone (3 mg/day) and dipyridamole (400 mg/day), and was shown to be superior to placebo. Assessments were performed at baseline and after 7, 14, 28 and 42 days, and included the Australian/Canadian osteoarthritis hand index (AUSCAN), visual analogue pain subscale (VAS) pain and patient global, and counts of distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal and carpometacarpal (CMC) joints (tenderness, soft tissue swelling, bony enlargement, limited motion). Various combinations of patient-reported outcomes and joint counts were computed as composite scores (similar to clinical disease activity index) and tested for responsiveness. For each measure, mean change from baseline to day 42, treatment effect, standardised response mean (SRM) and relative efficiency compared with AUSCAN pain were calculated. RESULTS: The SRM were largest for VAS patient global (0.92), VAS pain (0.77) and AUSCAN pain (0.68), whereas the responsiveness of tender (0.46) and swollen joint counts (0.51) (18 joint assessment of DIP, PIP, CMC) was similar to AUSCAN stiffness (0.53) and physical function (0.37). Composite scores showed similar responsiveness as patient-reported pain and global. CONCLUSION: Patient-reported pain and patient global assessment were the most responsive outcomes, whereas joint counts had similar responsiveness to patient-reported stiffness and physical function. Composite scores were as responsive as VAS pain, and these results encourage further elaboration and validation of composite scores in HOA in larger studies.
Asunto(s)
Antirreumáticos/uso terapéutico , Dipiridamol/uso terapéutico , Articulaciones de la Mano , Osteoartritis/tratamiento farmacológico , Prednisolona/uso terapéutico , Adulto , Anciano , Combinación de Medicamentos , Femenino , Articulaciones de la Mano/patología , Articulaciones de la Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Osteoartritis/fisiopatología , Dimensión del Dolor/métodos , Recuperación de la Función , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: The novel synergistic drug candidate CRx-102 comprises dipyridamole and low dose prednisolone and is in clinical development for the treatment of immunoinflammatory diseases. The purpose of this clinical study was to examine the efficacy and safety of CRx-102 in patients with hand osteoarthritis (HOA). METHODS: The study was conducted as a blinded, randomised, placebo-controlled trial at four centres in Norway. Eligibility criteria included being of age 30-70 years, at least one swollen and tender joint, a Kellgren-Lawrence (K-L) score of 2 or higher on radiographs, and a score of at least 30 mm pain on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) visual analogue pain scale (VAS). The primary endpoint was a reduction in pain from baseline to day 42 on the AUSCAN pain subscale. Two-sided p values for the differences in least squares (LS) means adjusted for baseline are presented. RESULTS: The mean age of the 83 patients with HOA was 60 years and 93% were females. CRx-102 was statistically superior to placebo at 42 days for changes in AUSCAN pain (LS mean -14.2 vs -4.0) and for clinically relevant secondary endpoints (joint pain VAS (-18.6 vs -6.3), patient global VAS (-15.9 vs -4.2)) in the intention to treat population. The most frequently reported adverse event during the study was headache (52% in CRx-102 vs 15% in the placebo group). CONCLUSIONS: The novel synergistic drug candidate CRx-102 demonstrated efficacy by statistically reducing pain compared to placebo in HOA and was generally well tolerated.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dipiridamol/uso terapéutico , Articulaciones de la Mano , Osteoartritis/tratamiento farmacológico , Prednisolona/uso terapéutico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Dipiridamol/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Dimensión del Dolor/métodos , Prednisolona/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled out-patient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean +/- SE, 528 +/- 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 +/- 76/h). Subsequent sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p less than 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (greater than or equal to 75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p less than 0.001). Sotalol reduced the median frequency of couplets by 94% (p less than 0.0001) and that of runs by 89% (p less than 0.0007). The electrocardiographic effects of sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proarrhythmic events or biochemical abnormalities were observed. In summary, sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.
Asunto(s)
Complejos Cardíacos Prematuros/tratamiento farmacológico , Sotalol/uso terapéutico , Anciano , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Electrocardiografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Distribución Aleatoria , Sotalol/administración & dosificación , Volumen Sistólico/efectos de los fármacosRESUMEN
Cardiac accumulation patterns of pyrophosphate labelled with techetium-99m (TcPyP) in rats one hour to 7 days after coronary artery ligation were studied by light microscopy, myocardial scintigraphy, imaging the isolated heart and by direct measurement of tissue activity. Results suggest that myocardial cells taking up TcPyP are irreversibly damaged and that the disappearance of TcPyP uptake coincides with the removal of necrotic cells by phagocytes.
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Difosfatos , Corazón/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagen , Tecnecio , Animales , Infarto del Miocardio/patología , Miocardio/patología , Cintigrafía , Ratas , Factores de TiempoRESUMEN
Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.
Asunto(s)
Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Nicardipino/uso terapéutico , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Ejercicio Físico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nicardipino/administración & dosificación , Nicardipino/efectos adversos , Postura , Distribución Aleatoria , Factores de TiempoRESUMEN
Two hundred thirty-four patients with supine diastolic blood pressure of between 95 and 114 mm Hg were enrolled into a double-blind, randomized, parallel, multicenter trial. The patients were randomized to either nicardipine 30 mg tid, propranolol 40 mg tid, or nicardipine 30 mg tid and propranolol 40 mg tid for six weeks. Two hundred six patients yielded data for analyses. Of the 28 not included, seven had missing data, whereas the remaining 21 were excluded because they either failed to meet inclusion criteria or were noncompliant at endpoint. Both nicardipine and propranolol as monotherapies and in combination achieved statistically significant, (P less than .01), supine diastolic blood pressure reduction relative to baseline. The combination of nicardipine and propranolol showed a greater reduction in supine diastolic and systolic measurements than either of the monotherapies. Nicardipine produced greater blood pressure reductions one hour after dosing, whereas the propranolol treatment tended to produce slightly greater blood pressure decreases eight hours after dose. The combination always resulted in the greatest blood pressure reduction, independent of time after dose. Adverse experiences were reported by 26% of patients in the nicardipine-treated group, most often transient vasodilatory effects, by 17% of the propranolol-treated patients, and by 18% of the combination-treated group. This study demonstrated at the doses studied that nicardipine alone produced equivalent blood pressure reductions to those obtained by propranolol alone, but that the combination of these two drugs produced greater reductions in blood pressures than either of the monotherapies.
Asunto(s)
Hipertensión/tratamiento farmacológico , Nicardipino/uso terapéutico , Propranolol/uso terapéutico , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nicardipino/administración & dosificación , Propranolol/administración & dosificación , Distribución AleatoriaRESUMEN
The investigation was designed to test whether nicardipine and tiapamil interact with digoxin, resulting in increased plasma digoxin levels. Ten patients mean age, 67 years) taking 0.13 mg to 0.25 mg of digoxin daily were given nicardipine (20 mg TID), and eight patients (mean age, 77 years) taking 0.13 mg to 0.25 of digoxin daily were given tiapamil (200 mg TID). Plasma levels of digoxin and nicardipine, heart rate, blood pressure, weight, serum electrolytes, and serum enzymes were measured and the electrocardiogram was monitored twice before, four times during, and once after the intervention with a calcium antagonist. No measurements of plasma levels of tiapamil were made. A chest roentgenogram was taken before, during, and after use of nicardipine or tiapamil. Mean plasma digoxin levels increased significantly in patients receiving tiapamil (P less than 0.01), but the values returned to normal after treatment with the experimental drug was discontinued. A wide variation of plasma nicardipine levels was observed, but there was no proportionate correlation between these levels and changes in digoxin levels. Blood pressure decreased significantly (P less than 0.01) and heart rate increased significantly (P less than 0.05) in patients receiving nicardipine. Similar changes in blood pressure and heart rate were not seen in patients receiving tiapamil. Although the use of each calcium antagonist led to an increase in plasma digoxin levels, the effect of tiapamil was greater than that of nicardipine.
Asunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Digoxina/sangre , Nifedipino/análogos & derivados , Propilaminas/efectos adversos , Anciano , Interacciones Farmacológicas , Electrocardiografía , Femenino , Humanos , Masculino , Nicardipino , Nifedipino/efectos adversos , Potasio/sangre , Clorhidrato de Tiapamilo , Factores de TiempoRESUMEN
BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. METHODS: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data. RESULTS: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05). CONCLUSION: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.
Asunto(s)
Antibacterianos/administración & dosificación , Minociclina/administración & dosificación , Periodontitis/tratamiento farmacológico , Enfermedad Crónica , Raspado Dental , Femenino , Humanos , Modelos Logísticos , Masculino , Microesferas , Persona de Mediana Edad , Periodontitis/terapia , Fumar , Resultado del TratamientoRESUMEN
BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.
Asunto(s)
Antibacterianos/uso terapéutico , Minociclina/uso terapéutico , Periodontitis/tratamiento farmacológico , Administración Tópica , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Cápsulas , Terapia Combinada , Intervalos de Confianza , Raspado Dental , Femenino , Estudios de Seguimiento , Hemorragia Gingival/tratamiento farmacológico , Hemorragia Gingival/terapia , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/efectos adversos , Oportunidad Relativa , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Pérdida de la Inserción Periodontal/terapia , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/terapia , Periodontitis/terapia , Vehículos Farmacéuticos , Seguridad , Factores Sexuales , Fumar , Resultado del TratamientoRESUMEN
In order to evaluate the negative inotropic effects of sotalol, metoprolol, and propranolol in patients with chronic stable angina pectoris, left ventricular ejection fraction (LVEF) was measured with radionuclide angiography and echocardiography. Fifteen patients entered the study, which was designed as a randomized crossover trial. The patients served as their own control at all times. Surprisingly, LVEF increased when measured by echocardiography in all three treatment periods, and decreased in the propranolol period when measured by radionuclide methods. The changes were not significant. There was no negative inotropic effect registered during any of the three drug treatments.
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Antagonistas Adrenérgicos beta/uso terapéutico , Angina de Pecho/tratamiento farmacológico , Angina de Pecho/diagnóstico por imagen , Presión Sanguínea/efectos de los fármacos , Volumen Cardíaco/efectos de los fármacos , Enfermedad Crónica , Ecocardiografía , Femenino , Humanos , Masculino , Metoprolol/uso terapéutico , Persona de Mediana Edad , Contracción Miocárdica/efectos de los fármacos , Propranolol/uso terapéutico , Cintigrafía , Sotalol/uso terapéutico , Volumen Sistólico/efectos de los fármacosRESUMEN
A method for the evaluation of the haemodynamic status of a patient with acute myocardial infarction is presented. Left ventricular ejection fraction has been considered to be an accurate indicator of haemodynamic status before and after therapy. A device for synchronising the R-wave, and controlling the recording oscilloscope during systole and diastole is described. The intention is to display both systole and diastole on one oscilloscope.
Asunto(s)
Presentación de Datos , Corazón/diagnóstico por imagen , Contracción Miocárdica , Conteo por Cintilación/instrumentación , Volumen Cardíaco , Diástole , Corazón/fisiopatología , Cardiopatías/diagnóstico por imagen , Humanos , Masculino , Cintigrafía , SístoleRESUMEN
Risk factors in elderly hypertensives: Recent large-scale clinical trials have shown that antihypertensive treatment in the elderly produces meaningful reductions in strokes and other cardiovascular events. However, the treatment of hypertension in older patients is often complicated by the presence of concomitant disorders. Clinical and silent myocardial ischemia, as well as left ventricular hypertrophy and both systolic and diastolic left ventricular dysfunction, frequently coexist with hypertension. Additional clinical considerations in elderly hypertensives include a high prevalence of abnormal lipid and glucose metabolism and a tendency toward decreased renal function. Effects of different antihypertensive drugs: Although diuretics and conventional beta-blockers have been used as first-line drugs in the major clinical trials, some of their effects on metabolic parameters and on the myocardium can make them inappropriate in some patients. Newer drug classes, including angiotensin converting enzyme (ACE) inhibitors, calcium-channel blockers and, more recently, alpha 1-adrenergic blockers are effective alternatives. Dual-acting beta-blockers offer an important new approach for treating hypertension in elderly patients. Effects of carvedilol: Carvedilol possesses both beta- and alpha 1-blocking activity and appears to exhibit calcium channel blocking activity in animals. The alpha 1-blocking properties of this drug help to produce a desirable hemodynamic profile and facilitate appropriate blood pressure and heart rate responses to exercise. Carvedilol does not appear to adversely affect left ventricular systolic function and, in selected patients with heart failure, has been shown to increase the ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Hipertensión/tratamiento farmacológico , Propanolaminas/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Anciano , Carvedilol , Cardiopatías/tratamiento farmacológico , HumanosRESUMEN
AIM: To summarize the risk factors associated with coronary heart disease and strokes and to evaluate measures used in the prevention and treatment of these diseases. METHOD: A review of the results of randomly allocated clinical trials of treatment for both primary and secondary prevention of coronary heart disease and strokes. RESULTS: Reductions in elevated blood pressure and cholesterol and cessation of cigarette smoking have clearly been shown to reduce the incidence of coronary heart disease. A reduction in blood pressure has also been shown to reduce the risk of strokes. In addition to other classical risk factors, such as abnormal serum lipids, diabetes and a genetic predisposition, recent studies have shown that elevated levels of fibrinogen and other clotting factors, elevated levels of renin and decreased levels of anti-oxidant vitamins such as E, C and beta-carotene can predict coronary heart disease and strokes. Thrombolytic therapy, aspirin and beta-blockers have been shown to reduce mortality in patients with myocardial infarction, and the latter two agents reduce mortality, re-infarction and strokes with long-term use. Treatment with intravenous magnesium and nitrates has shown promise but larger trials are required to confirm the results. Both aspirin and heparin have proven value in reducing the incidence of myocardial infarction and death in unstable angina. Following an acute myocardial infarction, long-term therapy with aspirin, beta-blockers, lipid-lowering agents and oral anticoagulants has been shown to reduce mortality and re-infarction. In patients with large infarcts associated with a low ejection fraction or heart failure, the use of angiotensin converting enzyme (ACE) inhibitors reduces mortality, hospitalization for heart failure and re-infarction. The use of diuretics to lower blood pressure reduces strokes. In contrast, calcium antagonists do not appear to consistently reduce mortality or prevent vascular events when used for primary or secondary prevention of either myocardial infarction or strokes. CONCLUSIONS: Myocardial infarction and strokes can be prevented by refraining from smoking and maintaining appropriate blood pressure levels and a favourable balance of lipids. Following a myocardial infarction, further drug treatment should include aspirin, thrombolytic therapy (in acute myocardial infarction), beta-blockers, ACE inhibitors (in patients with a low ejection fraction) and perhaps anticoagulants.
Asunto(s)
Trastornos Cerebrovasculares/prevención & control , Infarto del Miocardio/prevención & control , Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Trastornos Cerebrovasculares/etiología , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Infarto del Miocardio/etiología , Factores de RiesgoRESUMEN
BACKGROUND: A variety of methodologies and techniques converge on the notion that adults and children with attention deficit hyperactivity disorder (ADHD) have similar deficits, but there is limited knowledge about whether adult retrospective reports reflect similar genetic and environmental influences implicated in childhood ADHD. METHOD: DSM-IV ADHD symptoms were collected retrospectively from 3896 young adults participating in the National Longitudinal Study of Adolescent Health. Responses from this genetically informative sample of same- and opposite-sex twins and siblings were used to determine the magnitude of genetic and environmental influences. Possible gender differences in these effects were also examined. The degree of familial specificity of the genetic and environmental influences on the Inattentive and Hyperactive-Impulsive symptom dimensions was also determined. RESULTS: Additive genetic effects contributed moderately to DSM-IV Inattentive, Hyperactive-Impulsive and Combined ADHD subtypes (heritability estimates of 0.30-0.38). Individual-specific influences accounted for the remaining proportion of the variance. Both genetic and individual-specific environmental effects contributed to the covariation of Inattentive and Hyperactive-Impulsive symptomologies. CONCLUSIONS: Results from our genetic analyses agree with previous findings based on self-assessment of current and retrospectively reported ADHD symptoms in adolescents and adults. Large individual-specific environmental influences as identified here suggest that current questionnaires used for retrospective diagnoses may not provide the most accurate reconstruction of the etiological influences on childhood ADHD in general population samples.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Trastornos de la Conducta Infantil/genética , Trastornos Disruptivos, del Control de Impulso y de la Conducta/genética , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastornos de la Conducta Infantil/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Ambiente , Femenino , Humanos , Conducta Impulsiva/genética , Masculino , Modelos Genéticos , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Hermanos , Medio Social , Encuestas y CuestionariosRESUMEN
The antiarrhythmic effects of tiapamil were investigated in 48 patients, mean age 54, with acute myocardial infarction and ventricular arrhythmias. 9 had ventricular tachycardia, 6 ventricular fibrillation, and 33 multifocal premature ventricular contractions. Before and after therapy, ECG parameters, left ventricular ejection fraction (measured using 99mTc-labelled blood cells), and serum enzymes were recorded. Tiapamil was administered in a dose of 1 mg/kg i.v. (injection) followed by 25 micrograms/kg/min i.v. (infusion) until a 70% reduction in premature ventricular contractions was achieved. Thereafter, tiapamil was given in oral administration of 200 mg three times daily for 3 months. 13 patients did not respond to treatment. Of these, 5 had ventricular tachycardia and 4 ventricular fibrillation. 6 patients died and showed massive necrosis at autopsy. Premature ventricular contractions decreased by 70-90% in the remaining 35 patients (73%). Mean arterial pressure and heart rate decreased significantly, the left ventricular ejection fraction improved, and the P-R interval increased significantly. No side effects were observed. It is concluded that tiapamil has the propensity to control premature ventricular contractions in patients with acute myocardial infarction.
Asunto(s)
Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Lidocaína/farmacología , Infarto del Miocardio/complicaciones , Propilaminas/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Resistencia a Medicamentos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Persona de Mediana Edad , Contracción Miocárdica/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Taquicardia/tratamiento farmacológico , Clorhidrato de Tiapamilo , Fibrilación Ventricular/tratamiento farmacológicoRESUMEN
There have been conflicting reports on the safety of combining beta-adrenergic receptor blockers and Ca++-antagonists, especially verapamil, in the treatment of cardiovascular diseases. Warnings have been raised against additive negative chronotropic and inotropic effects. This study was designed to compare the efficacy and safety of simultaneous administration of verapamil, 360 mg daily, and atenolol, 100 mg daily, with that of either drug alone. Eighteen patients (mean age 58 years) with chronic stable angina were included in the study. After a two-week run-in period, the patients received either drug alone for six weeks and were then given the combination for another six weeks. Frequent ECG and blood pressure measurements were performed. Radionuclide evaluation of left ventricular ejection fraction was done before and at the end of the combined therapy. Exercise testing using a bicycle ergometer was performed during each treatment period. Only one patient developed sinus bradycardia when on combined therapy (48 bpm). The P-Q time increased with single drug therapy as well as with the combination (p less than 0.01). Maximal exercise time increased more with the combination than with single drug therapy. No serious adverse hemodynamic effects were recorded. LVEF increased by 4.6% (p less than 0.01) with the combined therapy. A decrease in nitroglycerine consumption occurred, beeing most pronounced with the combined therapy and corresponding to a subjective improvement. It is concluded that an additive negative chronotropism occurred but that the combination is safe and offers an effective therapeutic alternative in chronic stable angina.