Page 610 - Basic _ Clinical Pharmacology ( PDFDrive )

596 SECTION VI Drugs Used to Treat Diseases of the Blood, Inflammation, & Gout

imaging is needed, MRI should be performed prior to ferumoxy- sickle cell anemia, aplastic anemia, etc. Deferiprone rarely has been
tol therapy or alternative imaging modality used if needed soon associated with agranulocytosis; thus weekly monitoring of the
after dosing. The U.S. Food and Drug Administration (FDA) has CBC is required for patients treated with this drug.
issued a black box warning about risk of potentially fatal allergic
reactions associated with the use of ferumoxytol.
For patients treated chronically with parenteral iron, it is VITAMIN B 12
important to monitor iron storage levels to avoid the serious toxic-
ity associated with iron overload. Unlike oral iron therapy, which Vitamin B (cobalamin) serves as a cofactor for several essential
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is subject to the regulatory mechanism provided by the intestinal biochemical reactions in humans. Deficiency of vitamin B leads
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uptake system, parenteral administration—which bypasses this to megaloblastic anemia (Table 33–2), gastrointestinal symptoms,
regulatory system—can deliver more iron than can be safely and neurologic abnormalities. Although deficiency of vitamin B
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stored. Iron stores can be estimated on the basis of serum concen- due to an inadequate supply in the diet is unusual, deficiency of
trations of ferritin and the transferrin saturation, which is the ratio B in adults—especially older adults—due to inadequate absorp-
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of the total serum iron concentration to the total iron-binding tion of dietary vitamin B is a relatively common and easily
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capacity (TIBC). treated disorder.
Clinical Toxicity Chemistry
A. Acute Iron Toxicity Vitamin B consists of a porphyrin-like ring with a central
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Acute iron toxicity is seen almost exclusively in young children cobalt atom attached to a nucleotide. Various organic groups
may be covalently bound to the cobalt atom, forming different
who accidentally ingest iron tablets. As few as 10 tablets of any cobalamins. Deoxyadenosylcobalamin and methylcobalamin are
of the commonly available oral iron preparations can be lethal the active forms of the vitamin in humans. Cyanocobalamin
in young children. Adult patients taking oral iron preparations and hydroxocobalamin (both available for therapeutic use) and
should be instructed to store tablets in child-proof containers other cobalamins found in food sources are converted to the
out of the reach of children. Children who are poisoned with active forms. The ultimate source of vitamin B is from microbial
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oral iron experience necrotizing gastroenteritis with vomiting, synthesis; the vitamin is not synthesized by animals or plants. The
abdominal pain, and bloody diarrhea followed by shock, lethargy, chief dietary source of vitamin B is microbially derived vitamin
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and dyspnea. Subsequently, improvement is often noted, but B in meat (especially liver), eggs, and dairy products. Vitamin
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this may be followed by severe metabolic acidosis, coma, and B is sometimes called extrinsic factor to differentiate it from
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death. Urgent treatment is necessary. Whole bowel irrigation intrinsic factor, a protein secreted by the stomach that is required
(see Chapter 58) should be performed to flush out unabsorbed for gastrointestinal uptake of dietary vitamin B .
pills. Deferoxamine, a potent iron-chelating compound, can be 12
given intravenously to bind iron that has already been absorbed
and to promote its excretion in urine and feces. Activated char- Pharmacokinetics
coal, a highly effective adsorbent for most toxins, does not bind The average American diet contains 5–30 mcg of vitamin B daily,
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iron and thus is ineffective. Appropriate supportive therapy for 1–5 mcg of which is usually absorbed. The vitamin is avidly stored,
gastrointestinal bleeding, metabolic acidosis, and shock must also primarily in the liver, with an average adult having a total vitamin
be provided. B storage pool of 3000–5000 mcg. Only trace amounts of vitamin
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B are normally lost in urine and stool. Because the normal daily
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B. Chronic Iron Toxicity requirements of vitamin B are only about 2 mcg, it would take
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Chronic iron toxicity (iron overload), also known as hemochro- about 5 years for all of the stored vitamin B to be exhausted and
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matosis, results when excess iron is deposited in the heart, liver, for megaloblastic anemia to develop if B absorption were stopped.
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pancreas, and other organs. It can lead to organ failure and death. Vitamin B is absorbed after it complexes with intrinsic factor,
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It most commonly occurs in patients with inherited hemochroma- a glycoprotein secreted by the parietal cells of the gastric mucosa.
tosis, a disorder characterized by excessive iron absorption, and in Intrinsic factor combines with the vitamin B that is liberated from
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patients who receive many red cell transfusions over a long period dietary sources in the stomach and duodenum, and the intrinsic
of time (eg, individuals with β-thalassemia). factor–vitamin B complex is subsequently absorbed in the distal
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Chronic iron overload in the absence of anemia is most effi- ileum by a highly selective receptor-mediated transport system.
ciently treated by intermittent phlebotomy. One unit of blood can Vitamin B deficiency in humans most often results from malab-
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be removed every week or so until all of the excess iron is removed. sorption of vitamin B due either to lack of intrinsic factor or to
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Iron chelation therapy using parenteral deferoxamine or the oral loss or malfunction of the absorptive mechanism in the distal ileum.
iron chelators deferasirox or deferiprone (see Chapter 57) is less Nutritional deficiency is rare but may be seen in strict vegetarians
efficient as well as more complicated, expensive, and hazardous, but after many years without meat, eggs, or dairy products.
it may be the only option for iron overload that cannot be managed Once absorbed, vitamin B 12 is transported to the various cells
by phlebotomy, as is the case for many individuals with inherited of the body bound to a family of specialized glycoproteins, trans-
and acquired causes of refractory anemia such as thalassemia major, cobalamin I, II, and III. Excess vitamin B is stored in the liver.
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