Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it can be effectively controlled by interruption of the complement cascade. Particular monoclonal antibodies, discussed later in the article, have proven efficacy in many cases. AHUS is usually caused by chronic, uncontrolled activation of the complement system, a branch of the bodys immune system that destroys and removes foreign particles. The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death. The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane cofactor protein), or is occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components, for example anti–factor H antibodies. : 1933    Prior to availability of eculizumab (Soliris)and ravulizumab(Ultomiris), an estimated 33–40% of patients died or developed end-stage renal disease (ESRD) (despite the use of supportive care, e.g. plasmapheresis) with the first clinical bout of aHUS. Including subsequent relapses, a total of approximately two-thirds (65%) of patients died, required dialysis, or had permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI). Signs and symptoms
Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, confusion, fatigue, edema (swelling), nausea/vomiting and diarrhea. aHUS often presents with malaise and fatigue, as well as microangiopathic anemia.
One study found that caffeine increases the concentration over time curve of zolpidem by about 20% and furthermore found that caffeine cannot adequately compensate for the impaired cognition caused by zolpidem. Chemistry
Three syntheses of zolpidem are common. 4-methylacetophenone is used as a common precursor. This is brominated and reacted with 2-amino-5-methylpyridine to give the imidazopyridine. From here the reactions use a variety of reagents to complete the synthesis, either involving thionyl chloride or sodium cyanide. These reagents are challenging to handle and require thorough safety assessments. Though such safety procedures are common in industry, they make clandestine manufacture difficult. A number of major side-products of the sodium cyanide reaction have been characterised and include dimers and mannich products. History
Zolpidem was used in Europe starting in 1988, and was brought to market there by Synthelabo. Synthelabo and Searle collaborated to bring it to market in the US, and it was approved in the United States in 1992 under the brand name "Ambien". It became available as a generic medication in 2007.In 2015, the American Geriatrics Society said that zolpidem, eszopiclone and zaleplon met the Beers criteria and should be avoided in individuals 65 and over "because of their association with harms balanced with their minimal efficacy in treating insomnia." The AGS stated the strength of the recommendation that older adults avoid zolpidem is "strong" and the quality of evidence supporting it is "moderate."