Inocencia Martínez-Mir

Adverse drug reactions in children reported by means of the yellow card in Spain

OBJECTIVE To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.

Consumo de hierbas medicinales y medicamentos

Objetivo Dada la posibilidad de efectos adversos, interacciones con medicamentos e intoxicaciones por contaminantes entre consumidores de hierbas medicinales (HM), nuestro objetivo es describir el consumo de HM en usuarios de los centros de salud en tratamiento con medicamentos. Diseno Estudio observacional, transversal. Emplazamiento Trece centros de salud de la Comunidad Valenciana. Pacientes u otros participantes Usuarios, de sexo indistinto, mayores de 14 anos, seleccionados para un estudio de utilizacion de medicamentos para encontrar diferencias entre sexos. Mediciones y resultados principales. Las variables de estudio, edad, sexo, nivel educativo, consumo de medicamentos y uso de HM se recogieron desde la historia clinica, tarjeta de largo tratamiento y encuesta estructurada ad hoc. De los 812 usuarios, 801 consumen medicamentos. Toman HM, 159 (19,6%; IC del 95%, 16,9–22,3); edad media, 55,8 anos (DE, 16,5); mujeres, 58,5% (IC del 95%, 50,8–66,1). Consumen HM, 226 (media, 1,42; IC del 95%, 1,32–1,52); los varones consumen mas HM (p Conclusiones Uno de cada 5 pacientes en tratamiento con medicamentos consume HM por automedicacion. La administracion sanitaria y los medicos deberian informar de los riesgos para la salud y las contraindicaciones de estos productos.

Studies of the spontaneous motility and the effect of histamine on isolated myometrial strips of the nonpregnant human uterus: The influence of various uterine abnormalities

We investigated the spontaneous uterine activity of isolated corpus uteri myometrial strips from 30 patients with nonpathologic myometrium, 26 patients with uterine myoma, 23 patients with uterine adenomyosis, and three patients with uterine malignancy. We also investigated the influence of these conditions on the response of the uterus to histamine. The results show the same qualitative cyclic changes of the spontaneous motility of isolated myometrial strips throughout the menstrual cycle in all the abnormalities studied. These changes are characterized by a low amplitude and high frequency of spontaneous contractions in the proliferative phase and lower frequency with higher amplitude of contractions in the secretory phase. The isolated strips from patients with myomas present the highest spontaneous activity in reproductive age and preclimacteric women, but not in menopausal women. Histamine produced concentration-related contractions that are not significantly different in all the myometrial strips studied.

Transient ischemic attack secondary to hypertensive crisis related to Panax ginseng

1. Okamoto H, Teramura M, Kamatani N. Myelodysplastic syndrome associated with low-dose methotrexate in rheumatoid arthritis. Ann Pharmacother 2004;38:172-3. DOI 10.1345/aph.1D117 2. Pointud P, Prudat M, Peron JM. Acute leukemia after low dose methotrexate in a patient with rheumatoid arthritis. J Rheumatol 1993;20:1215-6. 3. Rosenthal NS, Farhi DC. Myelodysplastic syndromes and acute myeloid leukemia in connective tissue disease after single-agent chemotherapy. Am J Clin Pathol 1996;106:676-9. 4. Yetgin S, Ozen S, Saatci U, Bakkaloglu A, Besbas N, Kirel B. Myelodysplastic features in juvenile rheumatoid arthritis. Am J Hematol 1997;54: 166-9. 5. Nam E-J, Kang Y-M, Kang H-R, Kim J-H, Rho H-J, Lee M-K, et al. Rheumatoid arthritis associated with myelodysplastic syndrome: a case report. J Korean Med Sci 1999;14:319-22.

Influencia del sexo del paciente en la calidad de los medicamentos consumidos

Objetivo Analizar la relacion entre el sexo del paciente y la calidad del medicamento controlando por las variables predictoras mas relevantes. Diseno Estudio observacional transversal. Emplazamiento Trece centros de salud de la Comunidad Valenciana. Participantes Usuarios adultos, seleccionados por muestreo consecutivo. Mediciones principales Encuesta semiestructurada que recoge variables sociodemograficas, de utilizacion de medicamentos por problemas de salud, frecuentacion de los servicios y origen de la prescripcion. La calidad del medicamento se midio con el valor intrinseco (VI). Resultados De los 812 pacientes, 412 son mujeres. Los varones consumen mas medicamentos con VI elevado (VIE) y las mujeres mas de VI inaceptable. Las mujeres mayores de 45 anos consumen mas medicamentos de VI no elevado (VINE). El analisis multivariante pone de manifiesto: a) la prevalencia en las mujeres de uso de medicamentos de VINE es una vez y media mayor que en los varones, diferencias no significativas, y b) en el grupo de edad de 45-64 anos el sexo femenino se comporta como modificador de efecto aumentando la prevalencia en el consumo de medicamentos de VINE en dos veces y media respecto a los varones ajustado por frecuentacion, problemas de salud y origen de la prescripcion Conclusiones Se contribuye a clarificar la influencia del sexo en la calidad del medicamento al senalar la mayor probabilidad de consumir medicamentos de peor calidad por el hecho de ser mujer y tener entre 45 y 64 anos. Ademas, se demuestra el papel del origen de la prescripcion y los problemas de salud en la explicacion de este consumo diferencial.

Influence of hormonal treatment on the response of the rat isolated uterus to histamine and histamine receptor agonists.

The response of the isolated uterus to histamine and histamine agonists was investigated in progesterone- and oestrogen-treated rats. The uterine inhibitory responses to histamine and 4-methylhistamine (a histamine H2 receptor agonist) were similar in KCl-contracted uteri from progesterone- and oestrogen-treated rats. The histamine H1 receptor agonist, 2-pyridyl-ethylamine, produced a relaxant response only in progesterone dominant uterus. This was inhibited by the histamine H1 receptor antagonist. In the rat isolated uterus which was not preconstricted by KCl, neither histamine, 4-methylhistamine, nor 2-pyridyl-ethylamine produced any effect in the presence or absence of ranitidine. Ranitidine competitively antagonized the histamine-relaxant uterine response in oestrogen-treated rats (pA2 = 7.21 (6.83-7.58)), but not in progesterone-treated rats, except in the presence of clemizole (10(-7) M) when the pA2 value of ranitidine against histamine was similar to that obtained in oestrogen-treated rats (pA2 = 6.74 (6.64-6.85)). These results indicate that treatment with ovarian steroids influences responses mediated by the histamine receptors of the isolated rat uterus. Both histamine H2 and H1 receptors contribute to the uterine inhibitory effect of histamine in progesterone-treated rats.

Are the adverse drug reactions of amoxycillin and amoxycillin-clavulanic acid similar?

In an attempt to assess the relative toxicity of amoxycillin and amoxycillin–clavulanic acid, we compared the adverse drug reactions reports collected using the spontaneous reporting system of a Regional Drug Surveillance Centre of Spain for both drugs between November 1986 and December 1992. During the 7‐year period 1986–92, the 247 reports of amoxycillin–clavulanic acid represent twice the number of reports of amoxycillin alone, and the number of reports related with sales received concerning the association were higher than those concerning amoxycillin alone. The adverse effects classified as severe were quantitatively and qualitatively similar for both drugs and gastrointestinal and skin are the most common system–organ affected by both drugs. With amoxycillin–clavulanic acid there is a higher proportion of stomatological reactions reported and a later onset of adverse drug reactions related with oropharyngeal lesions, and the reaction of the resistance mechanism when compared with the other organs and systems affected. The duration of the adverse drug reactions to amoxycillin–clavulanic acid is longer than for amoxycillin alone. In conclusion: (i) the adverse drug reactions profile of both drugs is different; (ii) the higher reporting rate for amoxycillin–clavulanic acid may be due to more recent marketing; and (iii) amoxycillin–clavulanic acid produces proportionately more gastrointestinal and fewer skin adverse reactions than amoxycillin alone.

Calidad de la publicación de reacciones adversas a medicamentos en la sección de Cartas al Director de cuatro revistas españolas de medicina interna y medicina general

OBJECTIVE To assess the quality and relevance of adverse drug reactions (ADRs) published as Letters to the Editor (LE) in Spanish medical journals. DESIGN Observational study. PARTICIPANTS LE on adverse drug reactions published over 5 years (1994-98). SETTING Four Spanish medical journals (Medicina Clínica, Revista Clínica Española, Atención Primaria and Anales de Medicina Interna). MAIN MEASUREMENTS Patient characteristics, drugs, ADR, causality algorithm, minimum criteria, and publication relevance. RESULTS Out of 2244 LE, 204 (9.1%) reported ADRs, which included 235 cases. The therapeutic subgroups most commonly implicated were anticoagulants and antiplatelet drugs, antibiotics, and antineoplastic agents; 20.4% of the drugs were recently marketed. ADRs most commonly involved the nervous system (13.6%), liver (10.2%), skin and appendages (9.8%), general reactions (9.8%), and the digestive system (8.1%). The reactions were moderate in 50.2% of cases and severe/fatal in 34%. The mean causality algorithm value (5.9+/-2.2) was similar among journals. Of the ADRs, 28 (11.9%) were definitive, 182 (77%) possible or probable, and 26 (11.1%) improbable or conditional; 10.2% were unknown. There were no differences in the mean minimum publication criteria (9.5+/-1.2). Publication relevance was 3.2+/-1.6 points, and higher in Medicina Clínica. CONCLUSIONS ADRs constitute an important part of LE in the journals studied. The causal relationship is acceptable, the documentation quality is high, with few unknown reactions and ADRs to recently marketed drugs. Relevance is generally low, although greater in Medicina Clínica.

Effect of histamine on the longitudinal and circular muscle of the oestrogen dominated rat uterus

The response of the longitudinal and circular myometrial strips to histamine was studied in oestrogentreated rats. Histamine produced a dose-related inhibitory response in KCl-contracted longitudinal and circular uterine strips. Histamine was equipotent in producing the relaxant response but the maximal effect achieved in the longitudinal muscle was higher than the circular one. Ranitidine antagonized the histamine-induced relaxation with a similar dose ratio in both longitudinal and circular strips. Clemizole and reserpine treatment did not produce any modification of the dose-response curve to histamine. In the longitudinal and circular strips which were not preconstricted by KCl, neither histamine nor 2-pyridylethylamine, even in strips pretreated with ranitidine, produced any effect when added to the organ bath. Our results show that the response of histamine in both longitudinal and circular uterine layers of the oestrogen-treated rats are mediated exclusively by histamine H2-receptors.

Relaxant effect of dopamine on the isolated rat uterus.

SummaryThe effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (107–10−4 M) produced a concentration-dependent relaxation in the K+-depolarized rat uterus. On a molar basis, dopamine was about 500 times less potent than adrenaline in relaxing the uterus, the maximum degree of relaxation obtained with both drugs was the same. Pretreatment of the rats with reserpine (5 mg/kg) did not produce any modification of the dose-response curve to dopamine. Similarly, cocaine (3 × 10−6 M) failed to modify the relaxant effect of dopamine. The dopamine induced relaxation was inhibited by propranolol (10−9–10−7 M) in a dose-dependent manner. Prazosin (10−7 M), SCH 23390 (10−7 M) and sulpiride (10−7 M) did not affect the dopamine dose-response curve. In the isolated rat uterus which was not preconstricted by KCl neither dopamine nor adrenaline produced any effect when added to the organ bath. This lack of response to both catecholamines was present even in tissues pretreated with propranolol or sulpiride. It is concluded that dopamine produced a concentration-dependent relaxation of the uterus from diethylstilboestrol-treated rats by direct activation of beta-adrenoceptors. There was no evidence for indirect action (catecholamine release and neuronal uptake mechanisms) and specific dopamine receptor mediated relaxation and alpha-adrenoceptor mediated contractions have not been found in this preparation.