Antihistaminic and anticholinergic activities of mequitazine in comparison with clemizole

Abstract The antihistamine and anticholinergic properties of mequitazine have been investigated and compared with those of clemizole. Both mequitazine and clemizole antagonized the effect of histamine in guinea-pig ileum competitively, the pA2 values calculated by Schild plot were 9.95 ± 0.44 for mequitazine and 10.54 ± 0.44 for clemizole. Mequitazine at 10−7 M produced a parallel shift of the dose-response curve to acetylcholine in the rat duodenum, clemizole and the lower doses of mequitazine failed to modify the effect of acetylcholine. The potency of mequitazine and clemizole as H1-histamine blockers is similar, but only mequitazine at highest concentration used showed anticholinergic a…

Effect of histamine and histamine analogues on human isolated myometrial strips.

1. The effect of histamine and histamine H1- and H2-receptor agonists on isolated myometrium strips of premenopausal women has been examined. The effect of acetylcholine was also determined. 2. Histamine, 2-pyridylethylamine, 4-methylhistamine and acetylcholine, but not dimaprit, produced a concentration-related contractile response in human isolated myometrial strips. Histamine also produced a further contraction in human isolated myometrial strips precontracted with KCl (55 mM). 3. The contractile response to histamine was antagonized by the histamine H1-receptor antagonist, clemizole (0.1 microM) but was potentiated by the histamine H2-receptor antagonist, ranitidine (10 microM). Clemizo…

Farmacologia de la solifenacina

Departamento de Farmacologia. Facultad de Medicina y Odontologia. Universidad de Valencia. Valencia. Espana.Resumen.- Los antimuscarinicos son los farmacos de primera eleccion para el tratamiento del sindrome de vejiga hiperactiva y su relacion beneficio/riesgo depen-de en gran medida de la selectividad por los distintos subtipos de receptores muscarinicos. Solifenacina es el antimuscarinico que muestra mayor selectividad por los receptores M3 vesicales, lo que puede traducirse en una menor incidencia de reacciones adversas relacionadas con otros subtipos de receptor. Las vias metabolicas de los antimuscarinicos pueden influir en la eficacia y en la aparicion de interacciones. Solifenacina es …

Influencia de la edad gestacional en la contractilidad de los vasos coriónicos humanos in vitro

Resumen Los vasos placentarios humanos carecen de inervacion autonoma y, por lo tanto, la resistencia vascular debe ser controlada por factores humorales y mecanismos anteriores autocrinos o paracrinos. Estos factores pueden variar en las diferentes etapas de la gestacion; asimismo, la respuesta de los vasos placentarios puede ser diferente segun la edad gestacional. Se conocen diversas sustancias que, originadas en el feto, la madre o el cordon umbilical, pueden afectar al tono vascular fetoplacentario de forma directa o indirecta. Investigamos si la edad gestacional modifica la respuesta vascular in vitrode los vasos placentarios a unagente vasoconstrictor como el cloruro potasico (ClK).

Relaxant effect of dopamine on the isolated rat uterus.

The effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (10(7)-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 x 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 ma…

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. Raniti…

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 oestrogen-treated 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, neithe…

El diseño y las conclusiones del estudio ALLHAT

Hemodynamic impact of isobaric levobupivacaine versus hyperbaric bupivacaine for subarachnoid anesthesia in patients aged 65 and older undergoing hip surgery

Background The altered hemodynamics, and therefore the arterial hypotension is the most prevalent adverse effect after subarachnoid anesthesia. The objective of the study was to determine the exact role of local anesthetic selection underlying spinal anesthesia-induced hypotension in the elderly patient. We conducted a descriptive, observational pilot study to assess the hemodynamic impact of subarachnoid anesthesia with isobaric levobupivacaine versus hyperbaric bupivacaine for hip fracture surgery. Description Hundred twenty ASA status I-IV patients aged 65 and older undergoing hip fracture surgery were enrolled. The primary objective of our study was to compare hemodynamic effects based …

Are the Adverse Drug Reactions of Amoxycillin and Amoxycillin-Clavulanic Acid Similar?

UNLABELLED 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 gastrointesti…

La actividad de la renina plasmática. Papel de la inhibición directa de la renina

Resumen La renina es la enzima encargada de transformar el angiotensinogeno en angiotensina I, primer paso en la activacion del sistema renina-angiotensina (SRA). La actividad de la renina plasmatica (ARP) mide la capacidad de la renina para producir angiotensina I a partir de angiotensinogeno, se expresa como concentracion de angiotensina I generada por unidad de tiempo (ng/ml/h) y se utiliza para valorar el grado de activacion del SRA. Hay relacion entre valores de ARP y enfermedad cardiovascular. Se ha descrito que valores de ARP alta se asocian con mayor incidencia de infarto agudo de miocardio, perdida de funcion renal, peor pronostico de la insuficiencia cardiaca y aumento de la morta…

Isolated human chorionic vascular reactivity: Technical considerations for fresh preparations

1. 1. Sixty chorionic vascular rings from normal term placentas were immersed in an organ bath for isometric tension recording to study (A) the contractile response to 120 mM of potassium chloride (KCI) after adjustment and equilibration to 1–5 g of passive tension; and (B) the concentration-response curve to KCI after adjustment and equilibration to the optimal passive tension. 2. 2. Adjustment to 4 g of passive tension elicited the maximal (P<0.007) and the latest (P<0.006) KCl-induced contraction among arterial rings. Venous rings showed the greatest contraction when adjusted to 3 g, but the differences were not significant except when compared to 1 g of passive tension (P<0.03). 3. 3. T…

Effects of dopamine in isolated rat colon strips.

The aim of the present work is to investigate the effects of dopamine on isolated rat colon strips, and whether dopamine receptors are involved in these effects. Experiments on spontaneous motility and under potassium contraction were performed with dopamine and isoprenaline, both in the absence and presence of antagonists (distal colon strips, isotonic recording, Tyrode solution, 31 °C, 1 g of resting tension). At higher concentration (10–4mol/L), dopamine abolished spontaneous motility of the rat colon and this effect was not modified by antagonists. In isolated rat colon strips that were depolarized with potassium, dopamine produced concentration-dependent relaxation, without significant…

Interacciones farmacológicas de los fármacos antihipertensivos

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admis…

Effects of Methoxamine on Spontaneous Uterine Activity and Blood Flow of the Rat Uterus &amp;lsquo;in vivo&amp;rsquo;

The vascular (blood pressure, heart rate and peripheral blood flow) and uterine (spontaneous motility) responses to intravenous methoxamine were studied in anaesthetized rats pre-treated with diethylstilboestrol. Methoxamine produced an increase (0.5-2 mg/kg) or did not modify (0.01 and 3 mg/kg) spontaneous uterine motility. The alpha 1-agonist also induced a hypertensive effect (0.1-3 mg/kg) accompanied by bradycardia at the highest doses, and a decrease in blood flow significantly greater in intestinal than uterine tissues. These effects were abolished by prazosin. The uterine action of methoxamine in vivo appears to result from the balance between myometrial alpha 1-excitatory effect and…

The Effects of Epinine on Arterial Blood Pressure and Regional Vascular Resistances in Anesthetized Rats

1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure r…

Identification of α2-adrenoceptors and non-adrenergic idazoxan binding sites in rabbit colon epithelial cells

alpha 2-Adrenoceptors are possibly involved in the regulation of the hydroelectrolytic flux across the digestive mucosa. As no data are available concerning the existence of these receptors in colon epithelial cells, we aimed to investigate the existence of alpha 2-adrenoceptors in this tissue using tritiated antagonists. [3H]Yohimbine and [3H]rauwolscine were not usable to label colonic alpha 2-adrenoceptors because of their very high level of non-specific binding. In contrast, the methoxy derivative of idazoxan, [3H]RX821002, appeared a convenient radioligand for the purpose. [3H]RX821002 bound with high affinity (KD = 6.2 +/- 0.8 nM) to a single population of non-interacting sites (Bmax …

Histamine inhibits spontaneous activity of the uterus of the progesterone-treated rat

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital

1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequen…

Response to dopamine agonists of the rat isolated uterus.

1. Quinpirole did not produce any effect in isolated uterus from oestrogenized rats even when it is contracted by KCl (37 mM). 2. Fenoldopam produced a relaxant effect on rat isolated uterus contracted by KCl which was not significantly modified by SCH 23390. 3. Reserpine decreased the effect of the lowest doses of fenoldopam. In reserpinized rats, propranolol (10(-9), 10(-8), 10(-7) M) antagonized the effect of the lowest doses of fenoldopam and neither SCH 23390, sulpiride nor ranitidine modified the effect of fenoldopam. 4. The results confirm our previous finding that DA1-receptors are not functional in our preparation. The effect of fenoldopam was partially due to a catecholamine-relea…

Interacciones medicamentosas. Nuevos aspectos

Se denomina interaccion farmacologica a la modificacion cuantitativa o cualitativa del efecto de un farmaco causada por la administracion simultanea o sucesiva de otro. La polimedicacion facilita la aparicion de interacciones cuyo resultado puede ser una reaccion adversa o la perdida de efecto terapeutico. La incidencia es dificil de determinar, pero se relaciona fundamentalmente con el numero de farmacos administrados conjuntamente al mismo paciente. Aunque es imposible recordar todas las interacciones de interes clinico, conocer su existencia y mecanismos de produccion ayuda a identificarlas y prevenirlas. Las que con mayor frecuencia causan problemas son las de tipo farmacocinetico, sobr…

Reactivity of isolated human chorionic vessels: analysis of some influencing variables

The aim of the study was to determine whether 24 h of cold storage of samples, mode of delivery, and gestational age influenced in vitro human chorionic vascular reactivity (35 arteries and 34 veins). The following groups were compared: (i) fresh versus 24-h cold-stored (4 °C in Krebs–Henseleit solution) chorionic vascular rings from normal term placentas, (ii) fresh chorionic vascular rings from normal term placentas obtained after vaginal delivery versus those obtained after elective caesarean section, and (iii) fresh chorionic vascular rings from normal term placentas versus those obtained from preterm deliveries. Isometric recording of the concentration–response curve to KCl (5–120 mM)…

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 …

Study on the histamine-like activity of guanfacine

Abstract The effects of guanfacine have been studied on guinea-pig isolated atria and diethylstilboestrol-treated rat isolated uterus to determine whether it possesses histamine-like activity. Guanfacine produced a concentration-dependent negative chronotropic effect which was not modified by ranitidine (0.1 μM). In rat isolated uterus contracted by KCl, clonidine (5–5000 μM) produced concentration-dependent relaxation which was blocked by ranitidine (0.1 μM), but guanfacine only produced relaxation at high concentrations (100–1000 μM), and this was not affected by ranitidine (0.1 μM). It is concluded that guanfacine, unlike clonidine, does not produce effects due to activation of H2-recept…

Grado de conocimiento de la población de Teruel acerca de la vacuna frente al virus del papiloma humano

Resumen Objetivo El objetivo general de este estudio es averiguar el grado de conocimiento sobre la vacuna frente al virus del papiloma humano (VPH) en la poblacion de Teruel susceptible de recibir esta. Material y metodos Estudio descriptivo transversal. Se administro un cuestionario semiestructurado a la poblacion diana, ninas vacunadas o que iban a vacunarse y madres que las acompanaban. El tratamiento estadistico se realizo con el SPSS® 14. Resultados La cobertura de vacunacion en los centros de salud de Teruel es muy elevada. La mayoria de las ninas opino que el agente causal de dicha enfermedad era el cancer. La informacion sobre la vacuna frente al VPH se recibe por los medios de com…

Medicamentos utilizados en pediatría extrahospitalaria: ¿disponemos de información suficiente?

Objetivo: Analizar los medicamentos que reciben los pacientes pediátricos en el ámbito extrahospitalario y la información disponible sobre los mismos. Pacientes y métodos: Estudio transversal, observacional y descriptivo realizado en una muestra de pacientes menores de 14 años atendidos en urgencias del Servicio de Pediatría del Consorcio Hospital General Universitario de Valencia entre junio 2005 y agosto 2006. Se cuantifican y clasifican los medicamentos utilizados antes de acudir a urgencias y se analiza la información sobre su uso que contiene el Vademécum Internacional Medicom y la ficha técnica. Resultados: Se recogió información sobre 462 niños con media de edad de 5,2 años (interval…