RESUMEN
INTRODUCTION: In a study of the oral administration of a single dose of metformin to healthy participants, the estimated half-life (t½ ) for the elimination of the drug from erythrocytes was found to be 23.4 h (compared with 2.7 h for metformin in plasma). However, these pharmacokinetic indices have not been well defined in metformin accumulation. METHODS: We systematically reviewed all the data on plasma and erythrocyte metformin assays available in our centre. We then selected patients with a plasma metformin concentration ≥ 5 mg/l and in whom the metformin concentration had been remeasured once or more at least 5 days after admission. RESULTS: Twelve patients met the aforementioned criteria. All but one of these patients displayed generally severe lactic acidosis on admission (mean ± sd pH and lactate: 6.88 ± 0.35 and 14.8 ± 6.56 mmol/l, respectively) and 11 were treated with dialysis. The mean ± sd time interval between the first and last blood sample collections for metformin measurement was 8.3 ± 3.2 days (range 5-14 days). Five days after the first sample had been collected, metformin was still detectable in plasma and in erythrocytes in all patients. Metformin remained detectable for up to 13 days (both in plasma and in erythrocytes). The estimated mean terminal t½ for metformin in plasma and erythrocytes was 51.9 and 43.4 h, respectively. CONCLUSIONS: The prolonged elimination of accumulated metformin (even after dialysis therapy) challenges the traditional view that the drug clears rapidly because of a short half-life in plasma.
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Eritrocitos/metabolismo , Hipoglucemiantes/farmacocinética , Metformina/farmacocinética , Eliminación Renal , Acidosis Láctica/inducido químicamente , Acidosis Láctica/complicaciones , Acidosis Láctica/etiología , Acidosis Láctica/prevención & control , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/terapia , Anciano , Algoritmos , Sangre/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/terapia , Femenino , Semivida , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/metabolismo , Hipoglucemiantes/uso terapéutico , Masculino , Registros Médicos , Metformina/efectos adversos , Metformina/metabolismo , Metformina/uso terapéutico , Persona de Mediana Edad , Diálisis Renal , Índice de Severidad de la Enfermedad , Distribución TisularAsunto(s)
Artritis Psoriásica/complicaciones , Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Accidente Cerebrovascular/complicaciones , Ustekinumab/efectos adversos , Ustekinumab/uso terapéutico , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Accidente Cerebrovascular/tratamiento farmacológico , Terapia TrombolíticaRESUMEN
BACKGROUND: Heparin-induced bullous hemorrhagic dermatosis is a rare, recently described side-effect of subcutaneous heparin injection. We describe a patient simultaneously presenting distant haemorrhagic bullae and eczematous reaction at the low molecular-weight heparin (LMWH) injection sites. PATIENTS AND METHODS: Subcutaneous enoxaparin sodium was initiated in a 51-year-old patient and was replaced a few days later by tinzaparin sodium. Forty-eight hours later, annular, erythematous and vesicular plaques appeared at the injection sites (thighs). Small hemorrhagic bullae were noted on the abdominal skin at the same time. Skin biopsies revealed respectively eczematous dermatitis and an intraepidermal blister filled with red blood cells. Direct immunofluorescence was negative. Standard laboratory investigations and coagulation studies were unremarkable. Skin lesions disappeared ten days after discontinuation of LMWH. Patch tests and intradermal tests were negative. DISCUSSION: The case described herein shares the stereotypical clinical picture previously reported, namely small, multiple, haemorrhagic bullae on normal skin, appearing at remote sites five to 21 days after the start of subcutaneous heparin treatment. Despite the absence of clear management guidelines, it is obviously tempting to stop the heparin if there are too many bullae for fear of more clinically significant and dangerous mucous membrane lesions. The underlying physiopathological mechanism is poorly understood; no coagulation abnormalities were recorded. In addition, our patient presented an eczematous reaction at the injection sites, raising the possibility of a type IV hypersensitivity reaction. The association of these two cutaneous side effects of heparin is perhaps not purely coincidental.
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Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/inmunología , Hemorragia/inducido químicamente , Hemorragia/inmunología , Heparina de Bajo-Peso-Molecular/efectos adversos , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Humanos , Inmunidad Celular , Masculino , Persona de Mediana EdadRESUMEN
UNLABELLED: Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.
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Agonistas de Dopamina/efectos adversos , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Pergolida/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Intervalos de Confianza , Electrocardiografía , Femenino , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/patología , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/efectos de los fármacos , Oportunidad Relativa , Enfermedad de Parkinson/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: Mycophenolate sodium (Myfortic) is an enteric-coated formulation of the immunosuppressant therapy mycophenolic acid. We report a case of diffuse mouth ulceration in a patient treated with Myfortic presenting recurrence after another dose of drug. PATIENTS AND METHODS: We report the case of a 26-year-old female patient with systemic lupus erythematosus, initially treated with corticosteroids and mycophenolate mofetil, but which was stopped because of varicella-zoster dissemination and leucopoenia. She consulted for mouth ulcers occurring two weeks after the introduction of Myfortic. There were no signs of opportunist infection or lupus activity. Mucosal ulcerations disappeared when Myfortic was stopped. Several weeks later, the patient presented recurrence of mouth ulcerations after another treatment of Myfortic. DISCUSSION: Myfortic is a new enteric-coated formulation of mycophenolic acid developed to reduce gastrointestinal upset associated with Cellcept. In certain cases, Cellcept toxicity can present as a number of oral ulcerations. Direct toxicity is involved in these cases. This side effect has never been described with Myfortic. In our case, the distinctive characteristic is that the patient was never treated with Cellcept without mucosal toxicity despite equivalent systemic mycophenolic acid exposure.
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Inmunosupresores/efectos adversos , Ácido Micofenólico/efectos adversos , Úlceras Bucales/inducido químicamente , Adulto , Femenino , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Recurrencia , Comprimidos RecubiertosRESUMEN
Although the year 2005 has reinforced the therapeutic advances of 2004, with confirmation of certain concepts, the 'coxib affair' has continued to provoke arguments between pharmaceutical companies, licensing agencies as well as patients, some of whom have amalgamated into consumer groups to reject en masse placing any responsibility on the prescribers in favour of an attack on the drug licensing process itself. Among the cardiovascular drugs that will soon be licensed, only ivabradine in stable angina, and remodulin in primary pulmonary arterial hypertension are new. The therapeutic advances in 2005 regarding platelet aggregation and blood coagulation have been significant, in the human, scientific and commercial context, while hypertension has not been ignored. Another new development is the ever more precise notion of the metabolic syndrome, a target of choice for the pharmaceutical industry. The potential range of applications has been widened to include obesity, hypertension, diabetes, HDL cholesterol... The licensing authorities find themselves facing a hurdle to overcome, with novel combinations of drugs (ACE inhibitors, calcium blockers/statins, statins/aspirin, ARA2/calcium blockers...).
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Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Aprobación de Drogas , Humanos , Edición/tendenciasRESUMEN
The year 2004 was not marked by major pharmacological advances, but by confirmation of previous "evidence". Several innovative drugs for stable angina (ranolazine, ivabradine), some interesting results in acute coronary syndrome (PROVE IT study), some classic concepts (cannabinoid receptors and their antagonists such as rimonabant) applied to novel indications (treatment of obesity), hopes for the "sartans" revived in the light of new evidence (VALUE study), advances in the management of diabetes and hypertension (ASCOT and CARDS studies), nebivolol which is not just a betablocker but also produces the NO radical (is this why it decreased the mortality of heart failure in the elderly in the SENIOR study?). In contrast, although Chronadalate did not live up to expectations for coronary insufficiency, the year was marked above all by the much heralded withdrawal of Vioxx for increasing cardiovascular risk. The old adage: primum non nocere springs to mind.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Valina/análogos & derivados , Angina de Pecho/tratamiento farmacológico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/prevención & control , Humanos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Tetrazoles/uso terapéutico , Valina/uso terapéutico , ValsartánRESUMEN
PURPOSE: Extrapyramidal disorders associated with veralipride therapy are rarely reported and often due to a drug misuse. METHODS: We evaluated cases of extrapyramidal disorders associated with veralipride. Cases were extracted from the regional pharmacovigilance centre of Amiens database. From January 1, 1995 to September 30, 2004, cases were selected on the basis of the occurrence of extrapyramidal disorders under veralipride therapy. RESULTS: Seventeen cases of veralipride-induced extrapyramidal disorders were found. They consist of 16 menopausal women and one old man with LH-RH antagonist-induced hot flushes. Mean age was 61 years (48-73). Adverse effects were acute dyskinesia (n=2) or parkinsonian syndrome, which occurred after several months or years of treatment (n=15). Parkinsonism was associated with other extrapyramidal symptoms in 8 cases: tardive dyskinesia (n=6), postural tremor (n=3), myoclonia (n=1), and trunk dystonia (n=1). In all cases, outcome was favorable after drug discontinuation. In most cases the tablet-free interval was not respected: this may lead to prolonged striatal D2 receptors blockade. It must be added that the diagnosis was often delayed and patients were considered as suffering from idiopathic Parkinson's disease. CONCLUSIONS: Prescribers should be aware that veralipride is a neuroleptic and could induce potentially severe extrapyramidal disorders. Increase veralipride prescription is expected due to the recent restriction of hormonal replacement therapy for menopause. The physicians should also use veralipride according to the Summary of the Product Characteristics.
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Enfermedades de los Ganglios Basales/inducido químicamente , Sulpirida/análogos & derivados , Sulpirida/efectos adversos , Anciano , Acatisia Inducida por Medicamentos/etiología , Antagonistas de Dopamina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etiología , Estudios RetrospectivosRESUMEN
The purpose of the study was to compare the renal effects of low doses of exogenous dopamine to assess the responsiveness of renal dopaminergic receptors in normotensive and hypertensive subjects. Eight hypertensive patients and seven normotensive volunteer subjects were studied. Inulin and para-aminohippuric (PAH) clearances, natriuresis, and fractional excretion of sodium increased significantly after intravenous dosing with dopamine (2 micrograms/min/kg) in both groups. These increases were significantly higher in hypertensive than in normotensive subjects: 31.8% +/- 3.7% vs. 16.2% +/- 1.2% for inulin clearance (P less than 0.01), 83.3% +/- 10.5% vs. 41.1% +/- 3.4% for PAH clearance (P less than 0.01), and 331% +/- 38% vs. 216% +/- 26% for natriuresis (P less than 0.01). These findings suggest hyperresponsiveness to dopamine during hypertension. This enhanced response to exogenous dopamine can be considered as a further argument favoring the existence of a deficit in dopaminergic activity during hypertension. Dopamine also induced a significant reduction in blood pressure and increased heart rate in hypertensive subjects but no significant change in blood pressure and heart rate occurred in normotensive subjects.
Asunto(s)
Dopamina/farmacología , Hipertensión/metabolismo , Riñón/efectos de los fármacos , Adulto , Presión Sanguínea/efectos de los fármacos , Dopamina/metabolismo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Inulina/metabolismo , Masculino , Persona de Mediana Edad , Ácido p-Aminohipúrico/metabolismoRESUMEN
This prospective study, which included 320 patients, showed that total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, and triglycerides correlate with thoracic aortic atherosclerosis. Low-density lipoprotein cholesterol is identified as an independent predictor of thoracic aortic plaque related to the severity of thoracic aortic atherosclerosis.
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Enfermedades de la Aorta/diagnóstico , Arteriosclerosis/diagnóstico , LDL-Colesterol/sangre , Hipercolesterolemia/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Aorta Torácica , Enfermedades de la Aorta/sangre , Arteriosclerosis/sangre , Colesterol/sangre , HDL-Colesterol/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Ecocardiografía Transesofágica , Femenino , Enfermedades de las Válvulas Cardíacas/sangre , Enfermedades de las Válvulas Cardíacas/diagnóstico , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
This study of 416 patients identified age, male gender, smoking, diabetes, hypertension, and hypercholesterolemia as independent predictors of thoracic aortic atherosclerotic plaque. Age, smoking, hypercholesterolemia, hypertension, and diabetes were predictors of the severity and extent of thoracic aortic atherosclerosis.
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Aorta Torácica/diagnóstico por imagen , Arteriosclerosis/diagnóstico por imagen , Enfermedad Coronaria/etiología , Ecocardiografía Transesofágica , Factores de Edad , Anciano , Enfermedad Coronaria/diagnóstico por imagen , Ecocardiografía Transesofágica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Prospectivos , Factores de Riesgo , Factores SexualesRESUMEN
STUDY OBJECTIVES: Plasma homocysteine level is a risk factor for coronary events, stroke, and peripheral atherosclerotic disease. However, few data are available concerning the relationship between homocysteine level and severity of thoracic aortic atherosclerosis. We hypothesized in this multiplane transesophageal echocardiography (TEE) study that homocysteine level is a marker of the presence and severity of thoracic aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Risk factors, angiographic features, and TEE findings were analyzed prospectively in 82 valvular patients. MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Plasma levels of homocysteine, vitamin B(12), and folic acid were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, family history of coronary artery disease, and levels of homocysteine, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant predictors of the presence of thoracic aortic plaques. There was a positive correlation between the plasma homocysteine levels and the score of severity of thoracic atherosclerosis (r = 0.48; p = 0.0001) as well as between the homocysteine levels and the grades of severity of aortic intimal changes (p = 0.0008). Multivariate regression analysis revealed that homocysteine was an independent predictor of the presence and severity of thoracic aortic atherosclerosis. CONCLUSION: This prospective study indicates that plasma homocysteine level is a marker of severity of thoracic atherosclerosis detected by multiplane TEE. These findings emphasize the role of homocysteine as a marker of atherosclerotic lesions in the major arterial locations.
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Enfermedades de la Aorta/sangre , Arteriosclerosis/sangre , Homocisteína/sangre , Adulto , Anciano , Anciano de 80 o más Años , Aorta Torácica , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/diagnóstico por imagen , Arteriosclerosis/diagnóstico , Arteriosclerosis/diagnóstico por imagen , Biomarcadores/sangre , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Estudios Transversales , Ecocardiografía Transesofágica , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Vitamina B 12/sangreRESUMEN
The objective was to compare the compliance of hypertensive patients treated with captopril twice daily or trandolapril once daily. After a 2-week placebo period, hypertensive patients (diastolic BP 95-115 mm Hg) were randomly allocated to trandolapril 2 mg once daily or to captopril 25 mg twice daily for 6 months. Trandolapril and captopril were packed in electronic pill-boxes equipped with a microprocessor that recorded date and time of each opening (MEMS). Patients' compliance was assessed both by standard pill-count and by electronic monitoring. Blood pressure was measured using a validated semi-automatic device at the end of the placebo period and of the treatment period. One hundred sixty-two patients entered the study. Compliance data were evaluable for 133 patients (62 in the captopril group and 71 in the trandolapril group). Treatment groups were comparable at baseline except for age (P = .046). Using electronic pill-box, overall compliance was 98.9% in the trandolapril group and 97.5% in the captopril group (P = .002). The percentage of missed doses was 2.6% in the trandolapril group and 3.3% in the captopril group (P = .06). The percentage of delayed doses was 1.8% in the trandolapril group and 11.7% in the captopril group (P = .0001). The percentage of correct dosing periods, ie, a period with only one correct recorded opening, was 94.0% in the trandolapril group and 78.1% in the captopril group (P = .0001). Results were unchanged when adjusted for age. At the end of the study, 41% of patients in the trandolapril group and 27% in the captopril group (NS) had their blood pressure normalized (systolic BP <140 and diastolic BP <90 mm Hg). In this 6-month study, the electronic pill-box allowed refined analysis of compliance of hypertensive patients. Patients' compliance with once daily trandolapril was higher than with twice daily captopril. The between-group difference is mainly explained by an increase in delayed doses in the twice daily group.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/uso terapéutico , Embalaje de Medicamentos , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Cooperación del Paciente , Presión Sanguínea/efectos de los fármacos , Esquema de Medicación , Monitoreo de Drogas , Electrónica Médica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
In vitro experiments were designed to assess the inhibitory effect of the thiazide diuretic methyclothiazide (MCTZ) on contractile responses to norepinephrine (NE) of mesenteric rings from hypertensive patients and normotensive controls. Arteries were taken from portions of mesocolon from 24 patients: 13 hypertensives and 11 normotensives. Changes in the tension of mesenteric ring preparations were measured isometrically. Histologic studies showed that the arteries from hypertensive patients exhibited 1) a greater media thickness-to-lumen diameter ratio, 2) a smaller lumen diameter, and 3) identical media cross-sectional area as those of normotensive controls. At the physiologic level, the hypertensive and normotensive arteries display similar contractile responses to KCl and NE. Furthermore, our results indicate that MCTZ induces concentration-dependent inhibition of the vasoconstrictor responses to NE. This study provides evidence that hypertension is associated with the remodeling of the human mesenteric artery and that MCTZ is as efficient in inhibiting the contractile response induced by NE on hypertensive than on normotensive arteries.
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Hipertensión/fisiopatología , Arterias Mesentéricas/efectos de los fármacos , Meticlotiazida/farmacología , Norepinefrina/antagonistas & inhibidores , Inhibidores de los Simportadores del Cloruro de Sodio/farmacología , Vasoconstricción/efectos de los fármacos , Adulto , Anciano , Diuréticos , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana EdadRESUMEN
Diltiazem has been reported to decrease or not to affect digoxin elimination. The effects of diltiazem on steady state concentrations of digoxin was evaluated in eleven patients with congestive heart failure receiving this drug for at least two weeks. The mean trough digoxin was 1.11 +/- 0.18 ng/ml before the coadministration of diltiazem (180 mg/day). This concentration increased to 1.54 +/- 0.22 ng/ml after three days and to 1.54 +/- 0.23 ng/ml after seven days of coadministration (P less than 0.01). Clinically, no patient showed signs of digitalis toxicity. Creatinine clearance was unchanged. The present results show that when diltiazem is added to a regimen that includes digoxin, steady state concentrations of this glycoside may increase.
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Digoxina/sangre , Diltiazem/farmacología , Cardiopatías/sangre , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Digoxina/uso terapéutico , Interacciones Farmacológicas , Femenino , Cardiopatías/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed.
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Antibacterianos/efectos adversos , Clostridioides difficile , Enterocolitis Seudomembranosa/inducido químicamente , Clostridioides difficile/efectos de los fármacos , Enterocolitis Seudomembranosa/epidemiología , Enterocolitis Seudomembranosa/microbiología , HumanosRESUMEN
Injection of a small dose of yohimbine, an alpha 2-adrenoceptor blocking agent (0.1 mg X kg-1 i.v.) increased systolic blood pressure, heart rate and cardiac performance in anaesthetized dogs. A larger dose of this drug (1 mg X kg-1 i.v.) influenced the cardiovascular system in an opposite way. The tachycardiac effect of yohimbine was also observed when the drug was administered either into the vertebral artery or the cisterna magna of chloralosed dogs. The increase in heart rate was found to be due to an increase in sympathetic tone and to a decrease in vagal tone. Some data reported here suggest that yohimbine could impair central cardiovascular regulation by acting on the baroreceptor reflex pathway. Indeed, intracisternal administration of yohimbine at small doses (1) reduced the tachycardiac and pressor responses to carotid occlusion, (2) reduced the bradycardia produced by intravenous noradrenaline. It is also suggested from the results of this investigation that yohimbine decreases the vagal part of the bradycardia resulting from the stimulation of the aortic baroreceptors but not those resulting from the stimulation of carotid sinus baroreceptors. Intracisternal administration of yohimbine also produced a significant inhibition of the Bezold-Jarish reflex induced by intravenous veratridine.
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Hemodinámica/efectos de los fármacos , Yohimbina/farmacología , Animales , Aorta/fisiología , Presión Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Arterias Carótidas/fisiología , Seno Carotídeo/inervación , Perros , Femenino , Corazón/inervación , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Norepinefrina/antagonistas & inhibidores , Presorreceptores/efectos de los fármacos , Receptores Adrenérgicos alfa/fisiología , Reflejo/efectos de los fármacos , Nervios Esplácnicos/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Nervio Vago/efectos de los fármacosRESUMEN
Methyclothiazide (MCTZ), a thiazide diuretic, inhibits the contractile response induced by norepinephrine in aortic rings from 12-week-old spontaneously hypertensive rats (SHR). Although not modified by indomethacin, this inhibition was attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment. These results suggest that the MCTZ effects on the norepinephrine-evoked vascular response are mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. MCTZ was also found to alter the contractile response induced by the addition of Ca(2+) to a depolarizing solution, and this inhibitory effect was partially abolished by NOLA application. Our data led us to propose that MCTZ relaxes aortic rings, resulting in an endothelium-dependent relaxation phenomenon that could even be reinforced under high-K(+) depolarizing conditions.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Meticlotiazida/farmacología , Músculo Liso Vascular/efectos de los fármacos , Inhibidores de los Simportadores del Cloruro de Sodio/farmacología , Animales , Canales de Calcio/efectos de los fármacos , Diuréticos , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III , Nitroarginina/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
The purpose of the present study was to further characterize the alpha-adrenoceptors located on parasympathetic fibres. Segments of guinea-pig ileum were stimulated by transmural electrical pulses, and the ensuing contractions, which are due to the release of acetylcholine from postganglionic parasympathetic fibres, were monitored. Clonidine and tramazoline, which are thought to act preferentially on presynaptic alpha-adrenoceptors, reduced the contractions, whereas phenylephrine and methoxamine, postsynaptic alpha-adrenoceptor agonists, were ineffective. Contractions induced by acetylcholine were not changed by clonidine but were abolished by atropine. Yohimbine, piperoxan, phentolamine and the thymoxamine reversed or prevented the inhibitory effect of clonidine. Prazosin and AR-C239 did not antagonize this effect. The inhibitory effect of tramazoline was antagonized by piperoxan but not AR-C239 or by prazosin. Naloxone did not alter the action of clonidine, and piperoxan did not change the inhibitory effect of morphine. In conclusion, these experiments suggest the presence on cholinergic postganglionic fibres of both opiate receptors and alpha-adrenoceptors.. The latter appear to resemble more closely alpha 2-adrenoceptors than alpha 1-adrenoceptors.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Acetilcolina/farmacología , Animales , Clonidina/farmacología , Interacciones Farmacológicas , Estimulación Eléctrica , Femenino , Cobayas , Íleon/efectos de los fármacos , Técnicas In Vitro , Masculino , Morfina/farmacologíaRESUMEN
OBJECTIVES: Although the existence of a deep compartment for metformin has long been hypothesized, there is still little direct information concerning metformin distribution in individual tissues in man. The only available study involves chronic metformin therapy. In that study, the measurement of metformin in erythrocytes provided a reliable indicator of metformin distribution and of potential accumulation. To determine the kinetics of metformin in plasma and in erythrocytes after acute oral administration, we performed the present study in healthy subjects after a single oral dose of metformin and compared the pharmacokinetics parameters in erythrocytes to those in plasma. METHODS: Six nondiabetic participants took the study dose of 850 mg metformin at 8: 00 AM after a non-standardized breakfast (i.e., as recommended in clinical practice). Blood samples were collected for metformin measurement in plasma and in erythrocytes at 0, 1, 2, 3, 4, 6, 9, 24, 33, 48, 57, and 72 h. RESULTS: Maximum metformin concentration was attained at 3.0 +/- 0.3 h in plasma and 4.7 +/- 0.5 h in erythrocytes. This difference was not significant. Metformin concentrations peaked at a maximum almost 6 times higher in plasma than in erythrocytes (1.7 +/- 0.1 and 0.3 +/- 0.0 mg/l, respectively). However, because the elimination half-life of metformin was much longer in erythrocytes (23.4 +/- 1.9 h vs. 2.7 +/- 1.2 h), there was no difference in area under the curve between plasma and erythrocytes. The distribution volume (plasma) was calculated to be 146 +/- 11 l. Plasma and erythrocytes concentration-time curves showed that metformin was not detectable in plasma 24 hours after the oral administration, while it remained detectable in erythrocytes up to 48 hours. Metformin concentrations crossed approximately 13 hours after having reached their maximum values in plasma, approximately 16 h after metformin intake. CONCLUSION: Having demonstrated the rapid elimination of metformin from plasma and its slow disappearance from erythrocytes, the presents results should contribute to adjustment of metformin dosage to renal function, assessment of drug compliance, and retrospective analysis (when blood samples are drawn with delay) of the link between metformin and development of lactic acidosis. Most importantly, the present findings should help to ascertain the optimal dosage of metformin, particularly in elderly patients.