Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog

Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog. Previous studies have demonstrated that the fall in inulin clearance which occurs 3 hours after the intrarenal administration of norepinephrine can be markedly attenuated by the prior administration of intrarenal prostaglandin E2 (PGE). Since in the previous studies PGE led to a marked increase in both renal blood flow and solute excretion, we designed the present series of experiments to investigate whether an increase in renal blood flow, solute excretion, or other factors were responsible for the protective effect in the norepinephrine model. Two renal vasodilators, bradykinin and secretin, were evaluated initially. Bradykinin administration prior to norepinephrine administration had a protective effect similar to that previously found with PGE, whereas secretin did not. Both of these vasodilators increased renal blood flow to the same degree, but only bradykinin increased urine flow and solute excretion. The fall in inulin clearance 3 hours after the administration of norepinephrine was also attenuated by two diuretics (mannitol and furosemide) which tended to increase renal blood flow. In contrast, two natriuretic agents, which are also renal vasoconstrictors (chlorothiazide and benzolamide), had no protective effect. Further, chlorothiazide and benzolamide obvicited the protective effect of bradykinin. These studies demonstrate that there are several types of pharmacologic agents which can modify the magnitude of renal functional impairment resulting from extreme renal ischemia. Although the mechanism of the protective effects remain unclear, the findings are compatible with the view that the protective effect noted with PGE, bradykinin, mannitol, and furosemide may be related to an increase in osmolar excretion which occurred with administration of each of these agents. This potentially salutory effect (increased osmolar excretion), however, could be overcome by an agent (e.g., chlorothictzide or benzolamide) which also increased renal resistance prior to the administration of norepinephrine.Etude des facteurs qui modifient l'évolution de l'insuffisance rénale aiguë par la norépinéphrine chez le chien. Des travaux antérieurs ont démontré que la chute de la clearance de l'inuline qui survient 3 heures après l'administration intra-rénale de norépinéphrine peut être atténuée de façon importante par l'injection intrarénale préalable de prostaglandine E2 (PGE). Puisque dans les travaux antérieurs, la PGE a déterminé une augmentation importante à la fois du débit sanguin rénal et de l'excrétion de substances dissoutes, cette série d'expériences a pour but de savoir si une augmentation du débit sanguin rénal ou de l'excrétion de substances dissoutes ou bien d'autres facteurs sont responsables de l'effet protecteur dans le modèle de la norépinéphrine. Deux vasodilatateurs rénaux, la bradykinine et la secrétine ont été initialement étudiés. L'administration de bradykinine préalable à celle de norépinéphrine a un effet protecteur semblable à celui antérieurement observé avec la PGE alors que la secrétine n'a pas cet effet. Ces deux vasodilatateurs augmentent le débit sanguin rénal de la même façon, mais seule la bradykinine augmente le débit urinaire et l'excrétion de substances dissoutes. La chute de la clearance de l'inuline 3 heures après la norépinéphrine est aussi atténuée par deux diurétiques qui tendent à augmenter le débit sanguin rénal (mannitol et furosémide). Au contraire, deux agents natriurétiques qui sont aussi des vasoconstricteurs rénaux (chlorothiazide et benzolamide) n'ont pas d'effet protecteur. De plus, ces deux corps empêchent l'effet protecteur de la bradykinine. Ces études démontrent qu'il y a plusieurs catégories d'agents pharmacologiques qui peuvent modifier l'importance de l'altération fonctionnelle qui résulte d'une ischémie rénale extrême. Quoique le mécanisme de l'effet protecteur reste obscur, ces constatations sont compatibles avec l'idée que l'effet observé avec la PGE, la bradykinine, le mannitol et le furosémide puisse être lié à une augmentation de l'excrétion osmolaire qui est observée au cours de l'administration de chacun de ces corps. Cet effet bénéfique potentiel (l'augmentation de l'excrétion osmolaire) peut, cependant, être annulé par un agent (comme le chlorothiazide ou la benzolamide) qui augmente aussi la résistance rénale préalablement à l'administration de norépinéphrine

Recommendations for Improving the Health Care System--Pharmacology

Dr. Fadem introduces the increasing problem of unaffordable pharmaceuticals, and addresses that issue by discussing how health care could constructively help patients gain more access to pharmaceuticals. Dr. Fadem accomplishes this goal by discussing the history of the FDA, the process of drug development, the manufacturing of drugs, and the marketing of those drugs. The Article also discusses how stricter regulations in the U.S. than abroad often punish the U.S. patient since the same drug sold overseas can cost double for the U.S. consumer

The airborne dilemma

In December 2019, there were 44 cases of an atypical pneumonia found to be related to a novel coronavirus, SARS-CoV-2. The disease was classified as a global health emergency one month later and reached pandemic proportion by March 11, 2020. By October 2020, it had killed over 1,000,000 people. By April 2021, there were nearly 3 million deaths. Not only has this virus been costly in terms of life but has had lasting side effects. It has been difficult to contain, sometimes resulting in overloading of hospital critical care services and disruption of regular care. It has also devastated the economy, particularly sectors related to tourism and transportation. Even the Summer Olympics were postponed. We have had severe pandemics throughout our history, but the last one this devastating was the Spanish Influenza of 1918. The world was unprepared for this onslaught.</p

Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran

Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran.BackgroundParenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.MethodsThis multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.ResultsA total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.ConclusionSFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued