Article discussing withdrawal of extended-release hydromorphone from the U.S. market
Dihydromorphinones from morphine & analogues
United States DEAs perspective, including statistics on manufacture and prescription levels from 1998 to 2006
"When is a pain doctor a drug pusher? ", The New York Times, 17 Jun 2007
The loss of function mutation results in a phenotype that is different from that of a gain of function mutation, and these phenotypes are associated with two different forms of type 4 hemochromatosis. Loss-of-function mutations are more frequent and are associated with type 4A hemochromatosis. These mutations lead to a defect in the localization of ferroportin. Gain-of-function mutations are associated with type 4B and lead to production of ferroportin that resists negative regulation by hepcidin.Unlike other forms of hemochromatosis, which have a recessive pattern of inheritance, type 4 is an autosomal dominant disorder. The dominant inheritance pattern occurs in hemochromatosis type 4 because ferroportin is multimeric. Consequently, mutant ferroportin can associate with wild-type ferroportin in multimers and interfere with the function of normal ferroportin proteins. Pathophysiology
In normal iron regulation, iron is absorbed in the intestine, and ferroportin transports iron from the cells of the intestinal lining into the bloodstream. Iron in the bloodstream is then bound by transferrin, which carries the iron to target cells. Iron is stored in cells and blood serum in a protein called ferritin. Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. Ferroportin is upregulated in the reticuloendothelial macrophages after phagocytosis occurs so that iron from the degraded red blood cells can be released into the bloodstream and transported to other types of cells as needed. Hepcidin, a protein synthesized in the liver in response to iron or inflammation, is a regulator of ferroportin expression.