TAILIEUCHUNG - Chapter 100. Megaloblastic Anemias (Part 13)

Antifolate Drugs A large number of epileptics, who are receiving long-term therapy with phenytoin or primidone, with or without barbiturates, develop low serum and red cell folate levels. The exact mechanism is unclear. Alcohol may also be a folate antagonist, as patients who are drinking spirits may develop megaloblastic anemia that will respond to normal quantities of dietary folate or to physiologic doses of folic acid only if alcohol is withdrawn. Macrocytosis of red cells is associated with chronic alcohol intake even when folate levels are normal. Inadequate folate intake is the major factor in the development of deficiency. | Chapter 100. Megaloblastic Anemias Part 13 Antifolate Drugs A large number of epileptics who are receiving long-term therapy with phenytoin or primidone with or without barbiturates develop low serum and red cell folate levels. The exact mechanism is unclear. Alcohol may also be a folate antagonist as patients who are drinking spirits may develop megaloblastic anemia that will respond to normal quantities of dietary folate or to physiologic doses of folic acid only if alcohol is withdrawn. Macrocytosis of red cells is associated with chronic alcohol intake even when folate levels are normal. Inadequate folate intake is the major factor in the development of deficiency in spirit-drinking alcoholics. Beer is relatively folate-rich in some countries depending on the technique used for brewing. The drugs that inhibit DHF reductase include methotrexate pyrimethamine and trimethoprim. Methotrexate has the most powerful action against the human enzyme whereas trimethoprim is most active against the bacterial enzyme and is only likely to cause megaloblastic anemia when used in conjunction with sulphamethoxazole in patients with preexisting folate or cobalamin deficiency. The activity of pyrimethamine is intermediate. The antidote to these drugs is folinic acid 5-formyl-THF . Congenital Abnormalities of Folate Metabolism Some infants with congenital defects of folate enzymes . cyclohydrolase or methionine synthase have had megaloblastic anemia. Diagnosis of Cobalamin and Folate Deficiencies The diagnosis of cobalamin or folate deficiency has traditionally depended on the recognition of the relevant abnormalities in the peripheral blood and analysis of the blood levels of the vitamins. Serum Cobalamin This is measured by an automated enzyme-linked immunoadsorbent ELISA assay. Normal serum levels range 118-148 pmol L 160-200 ng L to 738 pmol L 1000 ng L . In patients with megaloblastic anemia due to cobalamin deficiency the level is usually 74 pmol L 100 ng L . In general

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