Tài liệu Color Atlas of Pharmacology (Part 13): Antianemics ppt

Drugs for the Treatment of Anemias

Anemia denotes a reduction in red

blood cell count, hemoglobin content,

or both. Oxygen (O2) transport capacity

is decreased.

Erythropoiesis (A). Blood corpus￾cles develop from stem cells through

several cell divisions. Hemoglobin is

then synthesized and the cell nucleus is

extruded. Erythropoiesis is stimulated

by the hormone erythropoietin (a gly￾coprotein), which is released from the

kidneys when renal O2 tension declines.

Given an adequate production of

erythropoietin, a disturbance of eryth￾ropoiesis is due to two principal causes:

1. Cell multiplication is inhibited be￾cause DNA synthesis is insufficient. This

occurs in deficiencies of vitamin B12 or

folic acid (macrocytic hyperchromic

anemia). 2. Hemoglobin synthesis is

impaired. This situation arises in iron

deficiency, since Fe2+ is a constituent of

hemoglobin (microcytic hypochromic

anemia).

Vitamin B12 (B)

Vitamin B12 (cyanocobalamin) is pro￾duced by bacteria; B12 generated in the

colon, however, is unavailable for ab￾sorption (see below). Liver, meat, fish,

and milk products are rich sources of

the vitamin. The minimal requirement

is about 1 µg/d. Enteral absorption of vi￾tamin B12 requires so-called “intrinsic

factor” from parietal cells of the stom￾ach. The complex formed with this gly￾coprotein undergoes endocytosis in the

ileum. Bound to its transport protein,

transcobalamin, vitamin B12 is destined

for storage in the liver or uptake into tis￾sues.

A frequent cause of vitamin B12 de￾ficiency is atrophic gastritis leading to a

lack of intrinsic factor. 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 cyanocobal￾amin or hydroxycobalamin (Vitamin

B12a; exchange of -CN for -OH group).

Adverse effects, in the form of hyper￾sensitivity reactions, are very rare.

Folic Acid (B). Leafy vegetables and

liver are rich in folic acid (FA). The min￾imal requirement is approx. 50 µg/d.

Polyglutamine-FA in food is hydrolyzed

to monoglutamine-FA prior to being ab￾sorbed. FA is heat labile. Causes of defi￾ciency include: insufficient intake, mal￾absorption in gastrointestinal diseases,

increased requirements during preg￾nancy. Antiepileptic drugs (phenytoin,

primidone, phenobarbital) may de￾crease FA absorption, presumably by in￾hibiting the formation of monogluta￾mine-FA. Inhibition of dihydro-FA re￾ductase (e.g., by methotrexate, p. 298)

depresses the formation of the active

species, tetrahydro-FA. Symptoms of de￾ficiency are megaloblastic anemia and

mucosal damage. Therapy consists in

oral administration of FA or in folinic

acid (p. 298) when deficiency is caused

by inhibitors of dihydro—FA—reductase.

Administration of FA can mask a

vitamin B12 deficiency. Vitamin B12 is re￾quired for the conversion of methyltet￾rahydro-FA to tetrahydro-FA, which is

important for DNA synthesis (B). Inhibi￾tion of this reaction due to B12 deficien￾cy can be compensated by increased FA

intake. The anemia is readily corrected;

however, nerve degeneration progress￾es unchecked and its cause is made

more difficult to diagnose by the ab￾sence of hematological changes. Indis￾criminate use of FA-containing multivi￾tamin preparations can, therefore, be

harmful.

138 Antianemics

Lüllmann, Color Atlas of Pharmacology © 2000 Thieme

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