Subject: PHARMACOLOGY First Semester A.Y.

2015-2016
Topic: 4.1 AGENTS USED IN ANEMIAS
Lecturer: Dr. Paguirigan

PRAYER BEFORE STUDYING o FERRITIN & HEMOSIDERIN

Holy Spirit, Giver of all good gifts, enter into my mind and heart.  Two storage proteins
Give me the gift of knowledge and the grace to use it wisely.  Deficiency of iron occurs most often:
Help me in all my endeavors. o In women because of menstrual blood loss
Give me perseverance and fortitude. o In vegetarians or malnourished individuals because of
Help my memory, that I may remember what I learn inadequate dietary iron intake
and recall it when necessary.
Guide me in the classroom.
You who are the Way, the Truth, and the Life,
Let me not be deceived by false teaching.
Our Lady of Good Studies, pray for me.
Amen.

TYPES OF ANEMIAS
 MICROCYTIC HYPOCHROMIC ANEMIA
o Caused by iron deficiency
o Most common type of anemia
 MEGALOBLASTIC ANEMIA
o Caused by a deficiency of Vitamin B12 or folic acid, cofactors
required for the normal maturation of red blood cells
 PERNICIOUS ANEMIA
o Most common type of Vitamin B12 deficiency anemia
o Caused by a defect in the synthesis of intrinsic factor, a
protein required for efficient absorption of dietary vitamin B12
 ANEMIAS CAUSED BY RADIATION OR CANCER CHEMOTHERAPY
o Involve suppression of bone marrow stem cells

PROTOTYPES REGULATION OF IRON STORES

 Regulation of body iron content occurs through modulation of
absorption in the intestine
 There is no mechanism for the efficient iron excretion
 As a result, failure of gastrointestinal regulation of iron
absorption is one cause of diseases associated with excess iron
stores
o eg. Hemochromatosis

ASORPTION OF IRON
 Absorbed as the ferrous ion and oxidized in the mucosal cell to
the ferric form
IRON
 Essential metallic component of heme STORAGE OF IRON
o HEME  TRIVALENT (FERRIC) IRON
 Molecule responsible for the bulk of oxygen transport in o Can be stored in the mucosa (bound to ferritin) or carried
the blood elsewhere in the body (bound to transferrin)
 Although most of the iron in the body is present in hemoglobin,  EXCESS IRON
an important fraction is bound to transferrin, and to ferritin and o Stored in protein-bound form as hemosiderin in the
hemosiderin reticuloendothelial system
o HEMOGLOBIN  An accumulation of hemosiderin occurs in hemolytic anemias
 Heme + Globin and hemochromatosis
o TRANSFERRIN o HEMOLYTIC ANEMIAS
 A transport protein  Anemias caused by excess destruction of red blood cells

Trans By: Tony Tagacay II Page 1 of 8

Edited By:
 ELIMINATION OF IRON
 Minimal amounts of iron are lost from the body with sweat and
saliva and in exfoliated skin and intestinal mucosal cells
 There is NO efficient method for excretion of excess iron
CLINICAL USES
 IRON DEFICIENCY ANEMIA
o The only indication for the use of iron
o Iron deficiency can be diagnosed from:
 Red blood cell changes
 Microcytosis, diminished hemoglobin content of blood
 Measurements of serum and bone marrow iron stores
o The disease is treated by:
 Dietary, ferrous iron supplementation
 In special cases, parenteral administration of iron dextran
 HEMOLYTIC ANEMIA
o Iron should NOT be given in hemolytic anemia because iron
stores are elevated and not depressed
TOXICITY OF IRON
SIGNS & SYMPTOMS
 ACUTE IRON INTOXICATION
o Most common in children
o Usually occurs as a result of accidental ingestion of iron
supplementation tablets
o Depending on the amount ingested and absorbed, the
following may result:
 Necrotizing gastroenteritis
 Shock
 Metabolic acidosis
 Coma
 Death
 CHRONIC IRON TOXICITY
o Occurs most often in:
 Individuals who must receive frequent transfusions
 eg. Patients with sickle cell anemia
 Those with hemochromatosis, an inherited abnormality of
iron absorption
TREATMENT OF ACUTE IRON INTOXICATION
 Immediate treatment is necessary and usually consists of:
o Removal of unabsorbed tablets from the gut
o Correction of acid-base and electrolyte abnormalities
o Administration of iron-complexing agents
 These iron-complexing agents include:
 Oral phosphate or carbonate salts (to precipitate
unabsorbed iron)
 Parenteral deferoxamine, which chelates circulating
iron
TREATMENT OF CHRONIC IRON TOXICITY
 Treatment of hemochromatosis is usually by phlebotomy, which
efficiently removes approximately 250 mg iron with each unit of
blood withdrawn
VITAMIN B12
 Cobalamin
 Cobalt-containing molecule
 Along with folic acid, a cofactor in the transfer of one-carbon
units, a step necessary for the synthesis of DNA
 Impairment of DNA synthesis affects all cells, but because red
blood cells must be produced continuously, deficiency of either
B12 or folic acid usually is manifested first as anemia
PHARMACOKINETICS
 Vitamin B12 is produced only by bacteria
o This vitamin cannot be synthesized by multicellular organisms
 It is absorbed from the gastrointestinal tract in the presence of
intrinsic factor
o INTRINSIC FACTOR
 A product of the parietal cells of the stomach
 Vitamin B12 is stored in the liver in large amounts
o A normal individual has enough to last 5 years
 PLASMA TRANSPORT
o Accomplished by binding to transcobalamin II, a glycoprotein
 When parenteral vitamin B12 is given, any in excess of the
transport protein binding capacity (about 50-100 μg) is excreted
 The two available forms of Vitamin B12, cyanocobalamin and
hydroxocobalamin, have similar pharmacokinetics
o HYDROXOCOBALAMIN
 Somewhat more firmly bound to plasma proteins
 Has a longer circulating half-life
PHARMACODYNAMICS
 Vitamin B12 is essential in two reactions:
o Conversion of methyl-malonyl CoA to succinyl-CoA
 Essential for lipid metabolism
 A deficiency of Vitamin B12 results in abnormalities of the
lipids essential for normal neuronal function
o Conversion of homocysteine to methionine
 Linked to folic acid metabolism and DNA synthesis
 Essential for normal production in red blood cells
CLINICAL USE & TOXICITY
 Vitamin B12 is available as hydroxocobalamin and
cyanocobalamin, which have equivalent effects
 Major application is in the treatment of naturally-occuring
pernicious anemia and anemia caused by gastric resection
 Because B12-deficiency anemia is almost always caused by
inadequate absorption, therapy should be parenteral
 Although oral therapy may suffice for maintenance, massive
doses must be used
 In addition to anemia, an important manifestation of Vitamin B 12
deficiency is the development of neurologic defects, which may
become irreversible if not treated promptly
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 o Treatment is by parenteral replacement of Vitamin B 12
 Because hydroxocobalamin avidly binds cyanide ion to form
cyanocobalamin, it has been also used successfully to treat
cyanide toxicity caused by nitroprusside
 Neither form of vitamin B12 has significant toxicity
FOLIC ACID
 Necessary for the synthesis of purines and for the formation of
thymidylic acid
 Because of the need for continuous production of red cells,
anemia is usually the first sign of folic acid deficiency
 In addition, deficiency of folic acid during pregnancy increases
the risk of neural tube defects in fetus
PHARMACOKINETICS
 Folic acid is also known as pteroylglutamyl acid
 It is readily absorbed from the gastrointestinal tract
 Only modest amounts are stored in the body, so a decrease in
dietary intake is followed by anemia within a few months
PHARMACODYNAMICS
 Folic acid is necessary for the transfer of one-carbon fragments
in the synthesis of purine and pyrimidine bases
 Therefore, it is most important for the health of rapidly-dividing
cells, in which DNA must be rapidly synthesized
o For the same reason, antifolate drugs are useful in the
treatment of various infections and neoplasms
CLINICAL USE & TOXICITY
 FOLIC ACID DEFICIENCY
o Most often caused by dietary insufficiency or by
malabsorption
 ANEMIA DUE TO FOLIC ACID DEFICIENCY
o Readily treated by oral folic acid supplementation
 FOLIC ACID SUPPLEMENTS
o Will also correct the anemia but not the neurologic deficits of
vitamin B12 deficiency
o Therefore, vitamin B12 deficiency must be ruled out before
folic acid can be chosen as the sole therapeutic agent in
megaloblastic anemia
 Folic acid has no recognized toxicity
BONE MARROW COLONY-STIMULATING FACTORS
 Almost a dozen glycoprotein hormones have been discovered
that regulate the differentiation and maturation of stem cells
within the bone marrow
 Three substances are now available, through recombinant DNA
technology, for the treatment of various conditions associated
with bone marrow depression
ERYTHROPOIETIN
 Produced by the kidney
 Reduction in its synthesis is responsible for the anemia of renal
failure
 The substance stimulates the production of red cells by
combination with specific receptors on erythroid progenitors in
the bone marrow
 Erythropoietin (epoetin alfa) is used for treatment of anemias
associated with renal failure and with bone marrow failure
o eg. Following transplantation or treatment with drugs that
are toxic to bone marrow
 The drug has also been used to accelerate the replacement of
red cells removed by phlebotomy
 TOXICITY
o Minimal
o Usually results from excessive increase in hematocrit
SARGRAMOSTIM
 Granulocyte-macrophage colony-stimulating factor, GM-CSF
 Stimulates the production of granulocytes and macrophages
 Used to accelerate the recovery of granulocytes after cancer
chemotherapy and other marrow-suppressing therapies
 Reduces the incidence of infection following bone marrow
suppression, presumably by strengthening natural defense
mechanisms
 Also stimulates production of red cells and platelets, though
these effects are of far less importance
 TOXICITIES
o Fever
o Arthralgias
o Capillary damage with edema
FILGRASTIM
 Granulocyte colony-stimulating factor, G-CSF
 Stimulates the production of neutrophils
 Much more selective than sargramostim, having no detectable
effect on cell lines other than granulocytes
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 Filgrastim’s clinical applications duplicate those of sargramostim
 Toxicity is minimal but can include bone pain

OTHER HEMATOPOIETIC GROWTH FACTORS

 Include:
o Monocyte colony-stimulating factor (M-CSF)
o Stem cell factor (SCF)
o Interleukins 3, 6, 9 and 11
 SCF and IL-3
o Have the broadest progenitor cell line effects including:
 Red cell
 Granulocyte
 Monocyte-macrophage
 Megakaryocyte
 Eosinophil
 Basophil
 None of these growth factors are currently available for clinical
use

PRAYER BEFORE EXAMINATION

Lord, thank you that you are with me right now
Your love surpasses all fear
I give you the anxiety I feel
I surrender all my worries to you

Clear my mind
Calm my heart
Still my Spirit
Relax my being
That I may always glorify you
In everything I write, speak and do
Amen.

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 Subject: PHARMACOLOGY First Semester A.Y. 2015-2016
Topic: 4.1 AGENTS USED IN ANEMIAS
Lecturer: Dr. Paguirigan

APPENDIX

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Trans By: Tony Tagacay II Page 5 of 8

Edited By:
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