Histamina, receptores de histamina e anti-histamínicos: novos conceitos / Histamine, histamine receptors and antihistamines: new concepts

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.

Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

Prurito / Pruritus

El prurito es la causa más común de consulta en Dermatología. En el presente articulo se hace una revisión de los estudios más relevantes sobre el prurito y se revisan la fisiopatogenia y la relación con enfermedades de distinto tipo. Es importante recalcar la relación entre el prurito y la respuesta del SNC, en lo que se ha llamado la inflamación neurobiológica. Establecemos una forma racional de enfrentar el prurito tanto desde el punto de vista de laboratorio como de terapéutica.

Pruritus is the most common symptom in dermatology. We present a review of the most relevant studies of pruritus its physiopathology and relations with other types of diseases. It is important to emphasize the relation between pruritus the CNS in what is known as neurobiological. Additionally we. Additionally we propase a rational means of facing pruritus from both laboratory and therapeutic perspectives.

Effect of indomethacin and tenoxicam alone and as adjutants to praziquantel on granulomatous reaction in experimental schistosomiasis: involvement of endogenous histamine

Granulomas formed in the liver or lung of man and animals with schistosomal infection are common manifestation of an inflammatory delayed hypersensitivity reaction. Non-steroidal antiinflammatory drugs [NSAIDs], indomethacine and tenoxicam have been used alone and as adjuvants to praziquantel in treating liver granulomas of Schistosoma mansoni infected mice. The size of granulomas, its histamine content and histamine forming capacity [HFC] have been measured at the end of the treatment with the above-mentioned drugs. Both of the antiinflammatory drugs effectively reduced the size of liver granulomas. The granuloma histamine content and HFC of the liver were increased by these drugs. The H2-antagonist [cimetidine] but not the H1-antagonist [diphenhydramine] counteracted the suppressive effect of NSAIDs on granuloma volume indicating that histamine may be involved in the direct immuno-regulatory effect exerted by NSAIDs on the granulomas via its immuno-suppressive properties. The combined therapy of either of the drugs with praziquantel did not result in any significant additional effect

Correlation of physiological stimulants of gastric secretion to the development of different types of gastric stress ulcers in male albino rats

Restraint, cold restraint, and water immersion stress were applied to pylorically ligated male albino rats in half hourly increasing duration [0.5-3.0 h]. All models of stress tested produced gastric ulcers, the indices of which were significantly correlated with the increased duration of stress exposure, with the increased gastric mucosal histamine, with the increased serum gastrin, and with the increased total acidity and proteolytic activity of gastric juice. The significant correlation between gastric mucosal histamine and serum gastrin supports a common mediator hypothesis for the former. Increased plasma epinephrine and norepinephrine correlated with the decreased volume of gastric secretion supporting decreased mucosal blood flow as a pathophysiologic factor while hypoglyceamia could not be considered as a vagal stimulant except with cold restraint since the other models showed hyperglyceamia

Central histaminergic involvement during stress in rats.

Effects of some drugs modulating central histaminergic (HA) transmission were evaluated on restraint stress (RS)-induced gastric ulcerogenesis, plasma corticosterone and immune responses in rats. RS for (i) 6 hr or (ii) 24 hr at room temperature, and (iii) 3 hr at 4 degrees C (CRS) all induced gastric mucosal erosions and elevated plasma corticosterone levels, the effects with the latter two RS procedures being most consistent. Pretreatment of rats with neuronal HA depletor, alpha-FMH (100 mg/kg, ip) attenuated both ulcer severity and corticosterone response, during both 24 hr RS and CRS. Similar effects were also seen with the mast cell degranulator, C-48/80 (10 micrograms/kg, i.c.v.) treatment. Further, the H1-blocker, pheniramine (25 mg/kg, ip) but not the centrally acting H2-blocker, zolantidine (5 mg/kg, ip) produced clearcut attenuations in both stress markers, during the experimental stressors. In rats immunized in SRBC, 24 hr RS (and not CRS) significantly prevented the humoral immune responses to the antigen. alpha-FMH, C 48/80 and pheniramine but not zolantidine, reversed this response during 24 hr RS. The results indicate a central HA ergic involvement in the visceral, endocrinal and immune responses during RS and suggest the probable role of both neuronal as well as extraneuronal (mast cell) HA and activation of H1-receptors in the mediation of these effects.

Histaminergic mechanisms in experimental convulsions.

Effect of some histamine (HA) agonists and antagonists were assessed on electroshock (MES) convulsions in mice and rats. In mice, pretreatment with the HA precursor, l-histidine (100, 500 and 1000 mg/kg) precipitated seizures after a subthreshold (30 mA) stimulus. Both incidence (%) and tonic hind limb extensor phase (THE) were more than that in vehicle treated controls. The H1 blockers, pheniramine (25 mg/kg) and promethazine (25 mg/kg) both protected against (60 mA) MES and both incidence of convulsions and THE were reduced. A similar protective effect was not seen with either the H2 blocker, cimetidine (up to 200 mg/kg), or atropine (1 mg/kg). In rats, both the classical antihistamines blocked MES seizures, whereas, the H2-blocker, cimetidine, and atropine were, ineffective. Further, both H1 blockers were ineffective in antagonizing seizures induced by pentylenetetrazole, INH, caffeine or strychnine. These results are discussed in light of a possible HA-ergic regulation of experimental convulsions.

Determinants of acid secretion.

Acid secretion is regulated by hormonal factors acting peripherally and centrally, as well as neural factors. Gastrin and histamine are the two most important peripheral hormonal stimulants, while the vagus is the predominant nerve affecting acid secretion. Meal related acid secretion occurs in three phases: cephalic, gastric and intestinal. Acid secretion is stimulated in the first two phases while it is inhibited in the intestinal phase. Proteins are potent acid stimulants but carbohydrates and fats are inhibitors. Tea, coffee, milk and alcohol are acid stimulants; on the other hand the damaging influence of spices on the stomach may not be related to increased acid secretion. Psychological stress has a variable effect. The effect of Helicobacter pylori infection on acid secretion is being elucidated. Many drugs modifying acid secretion are available and are useful in the treatment of acid peptic disease.

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.

El papel en la histamina en la respuesta inmune / The role of histamine in the immune response

Actualmente, se considera al sistema inmune dentro de un marco de interacciones celulares en las que participan tanto moléculas provenientes de linfocitos como de macrófagos/monocitos, que inducen tanto señales positivas como negativas que conllevan hacia una perfecta regulación de la respuesta. La producción por estas células de moléculas como las prostaglandinas, la histamina y los leucotrienos, así como la presencia de receptores para ellas, indican su papel como mediadores intercelulares que, junto con las linfocinas y las monocinas comúnmente conocidas, y de las que se diferencian por su estructura y por su amplia distribución en los tejidos, estarían participando dentro de esta intrincada red de interacciones celulares que, finalmente, conducirán hacia una respuesta adecuada. Fue así como se abrió una nueva área de investigación sobre el papel de estas moléculas, generalmente consideradas por su potencial de daño, como sustancias clave que están induciendo "señales finas" de regulación. A pesar de que la literatura sobre el tema es vasta, abundan los resultados contradictorios, que deben ser tomados en cuenta con sentido crítico. Con esta idea en mente, en esta revisión se trata de definir el papel de la histamina, las prostaglandinas y los leucotrienos en la respuesta inmune, haciendo siempre una breve consideración sobre la bioquímica de cada una de estas moléculas, lo que finalmente nos llevará a una mejor interpretación de los resultados

Açöes da histamina no sistema nervoso central / Action of histamine on central nervous system

Embora a histamina tenha sido um dos primeiros autacóides descobertos em seres humanos, suas atividades biológicas ainda näo foram totalmente esclarecidas, principalmente no que diz respeito ao sistema nervoso central. Sabe-se hoje que os seus efeitos envolvem a ativaçäo de dois tipos de receptores, e que säo conhecidos dois tipos de antagonistas: os anti-H1 e os anti-H2. É chamada atençäo para o fato que no sistema nervoso central sua distribuiçäo näo é uniforme, e, com exceçäo da hipófise, no hipotálamo encontra-se a concentraçäo mais alta de histamina. Há evidencias de que essa amina esteja, em grande parte, situada nos terminais nervosos, e desempenhe papel de neurotransmissor. Alguns efeitos fisiológicos da histamina no sistema nervoso central säo reestudados em fase dos reestudados obtidos como bloqueio seletivo de receptores H1 e H2. O posssível papel da histamina no mecanismo de açäo de algumas drogas é também sumariamente abordado. Os dados revistos confirmam que a histamina desempenha importantes funçöes no sistema nervoso central, e que novas pesquisas em muito contribuiräo para aprofundarem os conhecimentos a esse propósito

¿Existe una relación entre la depresión y la hipertension? / Is there a relationship between depression and hypertension?

La depresión es presentada en los pacientes hipertensos, con más frecuencia que en la población general. Los autores revisan las 4 hipótesis propuestas para explicar esta asociación y encuentran que la posibilidad de una relación etiológica entre las dos enfermedades es una hipótesis interesante pero que no está confirmada. En cambio la depresión puede ser un efecto secundario de ciertas drogas antihipertensoras que agotan las aminas cerebrales y, en otros casos puede ser una reaccióm psicológica contra una enfermedad crónica