133 Antianemics (Grugs for the Treatment of Anemias Anemia denotes a seduction in red blood cell count, hemoglobin content, ‘or both. Gxygem (03) transport capacity is decreased, Erythropoiesis (A). Blood carpus- des develop fram stem cells through several cell divisions. Hemoglobin is then synthesized and the cell nucleus is ‘extruded. Erythropoiesis is stimulated by the hormone erythrapoietin (a gly- coprnteim), which is released from the kidneys when renal Oz tension declines. Given an adequate production of erythropaietin, a disturbance of eryth- ropoiests és due to two principal causes 1 Cell multiplication is inhibited be- ‘cause DNA syathesis is insufficient. This ‘cccurs in deficiencees of wiiamm Bx or folic acd (macrocytic hyperchromic anemia). 2. Hemoglobin synthesis is This situation arses in iran j. Since Fe* is aconstituent of hemoglobin (microrytic hypochromic anemia). ‘Vitamin By: (8) ‘Vitamin. 6,2 (cyamocobalamin) is pro- duced by bacteria: By2 generated in the colon, however, is unavailable For ab- sorption (see below). Liver, meat, fish, and milk products are rich sources of ‘the vitamén. The minimal requirement is about 1 pgjd. Enteral absorption of vi- tamin B,2 requires so-called “intrinsic factor” from parietal cells af the stom- ach. The complex formed wath this gly- ‘coprotein undergoes eniacytasis in the ileum, Bound to its transport protein, transrobalamin, vitamin 8,3 is destined far storage in the liver ar uptake into tis- sues. "A Frequent cause of vitamin By de- ficiency is atrophic gastritis leading ta.a inck of trertnsic fortor. Besides megalo- blastic anemia, damage to mucosal lin- ings and degeneration of myelin sheaths with neurological sequelae will ‘occur (pernicious anemia}. Optimal therapy consists in paren- teral administration of cyamocobal- amin or hydroxycobalamin (Vitamin Biz; exchange of -CN far -OM group). Adverse effects, in the farm of hyper- sensitivity reactions, are very rare Folic Acid (B). Leafy vegetables and liver are rich in folic acad (FA), The: imal requirement is approx. 50 pgjd- Polyglutamine-FA in food is hytiroleed fo monaghutamine-FA prios to being ab- sorbed. FA is heat labile. Causes af defi- ciency include: insufficient intake, mal- absorption in gastrointestinal diseases, increased requirements during preg- nancy. Antiepileptic drugs (phenytoin, primsdone, phenobarbital) may de- (Crease FA absorption, presumably by in- hibéting the formation of monogiuta- mine-FA. Innibition of dihyare-FA re ductase (ef, Dy methotrexate, p. 298) depresses the formation of tne achive Species, tetrahydro-FA, Symptoms of he Fiency are megalablastic anemia and mucosal damage. Therapy consists in oral administration of FA or in folinsc ace (p. 296) when Geficiency & caused Dy imhabstors of dinydro—FA—rechactase. Administration of FA can mask a vitamin Bg deficiency. Vitamin Ba is te- quired for the conversion of mettiyltet- rahydro-FA to tetrahydro-FA, which és important for DNA synthesis (B). Inibi- tion of this reaction due to Bz deficien- cy can be compensated by increased FA intake. The anemia is readily corrected; however, nerve degeneration pragress- es unchecked and its cause is made more difficult to diagnose by the ab- sence of hematological changes. Indis- criménate use of FA-containéng rmultivi- famin preparations can, therefore, be harmful Lilimann, Color Atkas of Pharmacology © 2000 Thieme All rghts reserved. Usage subject to terme and conditions of license:eereeer é (eee