Drug Treatment of Anemias

DRUG TREATMENT
OF ANEMIAS
DR. MAH-E-NOOR
ASSISSTANT PROFESSOR PHARMACOLOGY
Objectives
At the end of this lecture, you should be able to understand:
 The basic concept regarding anemia e.g., it’s pathophysiology and types
(classification)
 Management and drug treatments of anemias
 Pharmacokinetics of important medicines
 Their MOAs as well as adverse effects
ANEMIA
Anemia is a condition characterized by low hemoglobin and RBC levels and the consequent signs and
symptoms appear due to reduced oxygen delivery to the tissues.
Types of Anemia - Classification
Haematinics
These are the agents required for the formation of blood and treatment of anemia.
Main haematinics include:
 Iron
 Vitamin B12 (cyanocobalamin)
 Folic acid
Erythropoiesis (RBC Formation)
Factors necessary for erythropoiesis:

1. Erythropoietin
2. Iron
3. Vitamin B12 (cyanocobalamin)
4. Folic Acid (folate)
5. Ascorbic acid (Vitamin C)
6. Pyridoxine (Vitamin B6)
Peginesatide is a new drug called erythropoiesis stimulating agent (ESA). It acts by

stimulating erythropoietin receptors. It is indicated for treatment of anemia due to
CRF in patients on dialysis.
Management of Anemias
Microcytic Normocytic Macrocytic
Iron deficiency anemia: Iron – Aplastic anemia: no Pernicious anemia: Vit. B12
only ferrous iron (sulfate, medication; may have to do injections
fumarate, gluconate). Ferric bone marrow transplant
iron is not absorbed Megaloblastic anemia: Folic
Renal disease: correct if
possible, otherwise renal acid and Vit. B12
transplant
Deficient RBC Production:
erythropoietin
Iron Deficiency Anemia (Microcytic)
Causes of iron deficiency anemia:
 Inadequate dietary intake of iron
 Partial gastrectomy
 Blood loss
 Malabsorption syndromes e.g., Celiac Disease
Rx:
 Treatment with oral iron should be continued for 3–6 months.
 The reticulocyte count should begin to increase in two weeks and peak in 4
weeks.
 Rise of hemoglobin level of blood by 0.5-1 g/dl per week is considered adequate
response to iron therapy.
 In pregnancy, iron should be started in the second trimester.
Treatment
Iron
Daily requirement of iron is
 Adult male: 1 mg
 Menstruating female: 2 mg
 Pregnant female: 3-5 mg
Total iron requirement can be calculated by the formula:

4.3 × Body weight (kg) × Hemoglobin deficit (g/dl)
For treatment of iron deficiency, the dosage recommended is 200 mg elemental iron
daily that can be obtained by giving 1000 mg of ferrous sulphate in three divided
doses providing around 60 mg elemental iron per dose [maximum tolerated dose].
Pharmacokinetics
Absorption:
 Iron is absorbed mostly in the duodenum in the ferrous form (Fe2+).
 Heme contains the iron in ferrous form and most of the inorganic iron is in ferric
form (Fe3+) which must be reduced to ferrous form for absorption by reducing
substances like ascorbic acid and gastric acid (HCl) increases the absorption.
Storage:
 When there is excess of iron in the body, it combines with apoferritin to form
ferritin, which remains stored in the mucosal cells or it is transported with
transferrin to be utilized in the formation of blood. It is removed from the body
when these cells are shed.
 Parenteral route (I.V., I.M.) is indicated only when
• Oral iron is not tolerated
• Oral iron is not absorbed
• Along with erythropoietin
 Iron-sorbitol-citrate should not be used intravenously because it will cause rapid

saturation of transferrin receptors, which can cause iron toxicity due to more free iron.
 Reasons for use: Renal failure, short bowel, celiac disease (sprue)
 Adverse effects of oral preparations: Nausea, gastric discomfort, constipation or
diarrhea, necrotizing gastroenteritis, metabolic acidosis and metallic taste (due to
elemental iron).
 Major problem with parenteral route: Pain at injection site and Pigmentation of
skin.
 Good idea is to start patients on small doses and increase gradually. Less side
effects are encountered that way. Intramuscular injections are usually given by z-
technique to avoid staining and pigmentation of skin.
Iron Poisoning:
 Occur in children due to accidental intake of large number of the iron tablets.
 The antidote of acute iron poisoning is deferoxamine. It is given by I.M.

injection.
 For chronic iron overload, as occurs in thalassemia patients, oral chelating

agent like deferiprone is preferred.
 DTPA and EDTA may also be used.

Megaloblastic Anemia (Macrocytic)
Causes of macrocytic anemia:
 Inadequate folate intake – alcoholics, teenagers, some infants
 Malabsorption – may be due to barbiturates, phenytoin, and oral contraceptives
 Impaired metabolism – may be due to methotrexate or rare enzyme deficiencies

Vitamin B12
 Also called the extrinsic factor. It’s deficiency leads to Megaloblastic anemia.
 This vitamin contains cobalt, cyanocobalamin and hydroxocobalamin. The forms

that are present in diet.
 Vitamin B12 must be ingested as it is not synthesized in body. It is present in

animal liver, kidney, meet, cheese, egg yolk etc. and legumes (microorganisms in
the nodules synthesize it).
 Vitamin B12 is released from the foods with the help of gastric acid and then it
combines with intrinsic factor (secreted by stomach), and the combination is
absorbed in terminal ileum.
 Deficiency also have manifestations related to loss of myelin like sub-acute
combined degeneration of spinal cord (symptoms of lesions of posterior column):
• Loss of vibration and proprioception
• Paranesthesia
• Depressed stretch reflexes
• Mental changes like poor memory and hallucinations etc.
 Vitamin B12 is used orally for treatment of megaloblastic anemia while through
I.M. or S.C. routes for pernicious anemia (due to deficiency of intrinsic
factor)
 Lack of Intrinsic Factor is called pernicious anemia.
 It is usually a result of an autoimmune disease that destroys the parietal cells of

the stomach.
 Lack of either vitamin B12 or folic acid prevents formation of DNA therefore,
RBC production does not occur or occurs abnormally.
 Macrocytic cells (large cells) which may have enough Hb, but are not concave
and are fewer in number. Therefore, cannot take up or transport oxygen normally.
The cells are more easily damaged – also contributing to the anemia
Folic Acid
 Deficiency of folic acid also results in megaloblastic anemia that is indistinguishable from
that due to vitamin B12 deficiency.
 It is given in treatment of megaloblastic anemia. It is also indicated in pregnancy to prevent

neural tube defects in the fetus. It should be started as soon as the pregnancy is diagnosed.
 Leucovorin (folinic acid, formyl THFA or citrovorum factor) can be used to prevent the
toxicity of methotrexate.
 If the cause of megaloblastic anemia is not known, folic acid alone should not be given
because it will correct the blood picture of anemia but neurological deficits due to vitamin
B12 deficiency may be aggravated (due to diversion of small amount of B12 left, in
correcting anemia instead of utilization in myelin formation).
Hematopoietic Growth Factors
Apart from nutritional agents, certain endogenous substances are required for proper
hematopoiesis; these substances are known as growth factors.
 Growth factor for RBCs is erythropoietin, Erythropoietin is secreted from kidney

and helps in the formation of red blood cells.
 For WBCs, it is granulocyte colony stimulating factor (G-CSF) and granulocyte
monocyte colony stimulating factor (GM-CSF) and
 For platelets these are thrombopoietin and IL-11
Erythropoietin – is used in anemia in
• Chronic renal disease prior to dialysis (there is always destruction of RBC in

dialysis as the blood goes through the dialysis pump)
• AIDS patients
• Transplant patients
• Cancer patients who have undergone chemotherapy that destroyed some of the
bone marrow.
• Surgical or extracorporeal procedures (e.g.,: CABG) because the pumps may have
destroyed many red blood cells.
• Premature children.
• Chronic inflammatory illnesses (e.g. systemic lupus erythematosus) in which
RBCs are destroyed.
 Recombinant human erythropoietin (Epoietin) is mainly useful for anemia due to
chronic renal failure and also due to bone marrow suppressing drugs like
zidovudine and anticancer drugs.
 Response is manifested as elevated hematocrit and reticulocyte count.
 Major adverse effect is polycythemia and hypertension.
 Darbepoetin alpha is long acting derivative having similiar indications.

Toxicities
Erythropoietin WBS growth factors Interleukin 11
• Hypertension • Fever • Fatigue

• Serious cardiovascular • Malaise • Headache
events • Bone pains • Dizziness
• Thromboembolic events • Myalgias • Anemia
• Stroke • Arthralgias • Dyspnea
• Mortality when • Capillary leak syndrome • Transient atrial arrhythmia
hemoglobin levels greater (peripheral edema, pleural • Hypokalemia
than 11g/dl and pericardial effusion)
• Pure red cell aplasia (rare) • Splenic rupture (rare)
THANK YOU
ANY QUESTION?

Drug Treatment of Anemias

Uploaded by

Copyright:

Available Formats

Drug Treatment of Anemias

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Drug Treatment of Anemias

Uploaded by

Copyright:

Available Formats

DRUG TREATMENT

At the end of this lecture, you should be able to understand:

Factors necessary for erythropoiesis:

Peginesatide is a new drug called erythropoiesis stimulating agent (ESA). It acts by

Total iron requirement can be calculated by the formula:

 Iron-sorbitol-citrate should not be used intravenously because it will cause rapid

 The antidote of acute iron poisoning is deferoxamine. It is given by I.M.

 For chronic iron overload, as occurs in thalassemia patients, oral chelating

 DTPA and EDTA may also be used.

 Inadequate folate intake – alcoholics, teenagers, some infants

 Malabsorption – may be due to barbiturates, phenytoin, and oral contraceptives

 Impaired metabolism – may be due to methotrexate or rare enzyme deficiencies

 This vitamin contains cobalt, cyanocobalamin and hydroxocobalamin. The forms

 Vitamin B12 must be ingested as it is not synthesized in body. It is present in

 It is usually a result of an autoimmune disease that destroys the parietal cells of

 It is given in treatment of megaloblastic anemia. It is also indicated in pregnancy to prevent

 Growth factor for RBCs is erythropoietin, Erythropoietin is secreted from kidney

• Chronic renal disease prior to dialysis (there is always destruction of RBC in

 Response is manifested as elevated hematocrit and reticulocyte count.

 Major adverse effect is polycythemia and hypertension.

 Darbepoetin alpha is long acting derivative having similiar indications.

Erythropoietin WBS growth factors Interleukin 11

• Hypertension • Fever • Fatigue

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.