anti anemia drugs

8/11/2019 Anti Anemia Drugs

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Anemia

2ndmost presenting manifestation of disease,with pain being the first.

It is defined as: low hemoglobin, low RBC countand low RBC mass.

Usually presents with pallor, fatigability,weakness and pale conjunctivae

In order to properly treat the anemia, you mustdetermine the cause.


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Causes of Anemia

1. Diminished production and orreplacement of red blood cells.

2. Excessive breakdown and loss of redblood cells.

Hemodilution while not a cause of anemia,it does cause an anemia-like effect.


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1. Diminished Production/Replacementof RBCs Anemia's

Microcytic anemiadeficiency of Fe RBCs appear pale and smaller, and we see more

reticulocytes in circulation.

Can be caused by the chronic use of aspirin, which

irritates the stomach GI blood loss.

Normocytic anemiadeficiency of Erythropoietin Caused by compromised renal function.

Macrocytic Anemia- deficiency of folic acid andB12

Diminished cell division and release of larger cells incirculation.


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2. Breakdown of RBCs Anemia

Bleeding: can be due to an ulcer or in femalesblood loss due to their menstrual cycle

Use of drugs that irritate the GI tract (aspirin)

Hemolysis (Hemolytic Anemia) can be causedby:

Autoimmune disease Mechanical (heart valves, microvascular disease)

Toxins (e.g., snake venom)


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Sites of action for EPO


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Therapeutic Uses of EPO

Anemia of end stage renal disease

To treat AIDS anemia caused by AZTs

suppression of bone marrow

Anemia related to cancer chemotherapy

Others To increase RBC levels for autologous blood donation

Anemia associated with rheumatoid arthritis


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Biological Actions of OtherHematopoietic Growth Factors

1. Granulocyte/Macrophage Colony Stimulating Factor(GM-CSF)- Sargramostim

Acts synergistically with IL-3 to stimulate the formation andproliferation of colony forming cells: CFU-GEMM, BFU-E,CFU-Meg, CFU-GM, CFU-M, CFU-E

Increases cytotoxic phagocytic activityof maturegranulocytes

2. Interleukin 3 (IL-3) Acts synergistically with GM-CSFto stimulate the formation

of granulocytes, macrophages, eosinophils andmegakaryocytes.

Acts synergistically with EPOto stimulate formation of BFU-Ecolonies

Induces CFU-S and leukemic blast cells into cell cycle


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More Hematopoietic Growth Factors

3. Colony stimulating Factor-1 (CSF-1 or M-CSF)Acts synergistically with GM-CSF and IL-3 to stimulate

monocyte/macrophage colony formation and function

4. Granulocyte Colony Stimulating Factor(G-CSF) - filgrastim

Acts synergisticallywithIL-3, GM-CSF and CSF-1to

stimulate formation of megakaryocytes, granulocyte-macrophage and high proliferative potential (HPP) colonies

Induces release of granulocytes from marrow


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More Hematopoietic Growth Factors

5. Thrombopoietin (TSF) Increases the size and number of megakaryocytes.

(IL-11 also useful in stimulating production)

Increases the concentration of early megakaryocytes cells(SACHE+cells) in bone marrow.

Produces an increase in megakaryocytes endomitosis.

Increases platelet size and number in plasma.


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Iron Cycle 5 - 10%of ingested iron

is absorbed

Once ingested the acidin the stomach:

1. Aids in ionizationof iron 2. Splits chelated

food ironfromchelator

3. Maintains ironin

soluble form 4. Allows iron to

remain in theabsorbable formFe3+


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Mechanism of Iron Absorption


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Therapeutic uses of Iron

Iron Deficient Anemia

Pregnancy

Premature Babies

Blood loss

Hookworn infestation

Malabsorption

Syndrome

GI Bleeding due to:

Ulcers Aspirin

Excess consumption ofcoffee


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Iron Preparations Oral Iron

Ferrous Sulfate(Feosol)300 mg tid Side Effects are extremely mild:

Nausea, upper abdominal pain, constipation or diarrhea.

Cheapestform of Iron and one of the most widely

used

Parenteral Iron Dextran(Imferon)IM or IV

Indicated for patients who cannot tolerate or absorboral ironor where oral iron is insufficient to treat thecondition ie. Malabsorption syndrome, prolongedsalicylate therapy, dialysis patients


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Toxicity of Iron Overdose

5000 deaths/yearin the US, usually in children

20% of children presenting with iron toxicity will

die

1 to 2 grams are sufficient to cause death

At high doses, Iron is absorbed through passivediffusion with no regulation


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IronClinical Effects

Early changes Vomiting, diarrhea Blood Volume HR TPR (reflex) Acidosis from Iron oxidation, Krebs cycle and

anaerobic metabolism citric acid and lactic acid

Intermediate changes Improvement (short lived) profound shock and CV

Collapse Hepatic Failure, jaundice, pulmonaryedema and death

Late Stage Intestinal scarring, fatty acid degeneration of liver,

cirrhosis and death.


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Treatment of Iron Overdose

ABCs supportive care

Bicarbonate for acidosis

Fluidsfor blood loss

Ipecac or lavage

Chelation with Deferoxamine


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Vitamin B12

Source: In food, especially in liver and kidneys. GIMicroorganism synthesis, Vitamin Supplements(Cyanocobalamin)

Necessary for normal DNA synthesis

Absorption of B12

1. Intrinsic Factor (low dose): a protein made by stomachparietal cells that binds to B12 and delivers it from the ileumvia a calcium mediated event.

2. Mass Action (High dose): 1000mg/day, absorbed viapassive diffusion


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B12Deficiency

A B12deficiencywill cause peripheral neuropathyand a macrocytic anemia, a pernicious anemia.

Folic Acidadministration can correct themacrocytic anemia but will fail to correcttheperipheral neuropathy.

To treat the neuropathy, Vit B12must be utilized.


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Mechanism for PeripheralNeuropathy

Cobalamin is a cofactor for the enzymeMethylmalonyl-CoA mutase which convertsmethylmalonyl-CoA to succinyl-CoA.

Succinyl-CoA enters the Krebs cycles and goesinto nerves to make myelin.

If no Vitamin B12, methylmalonyl-CoA goes on to

form abnormal fatty acidsand causes subacutedegeneration of the nerves. Only B12cancorrect this problem.


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Therapeutic Uses of B12 Daily Requirements - 0.6-1.0mh/day; T1/2~ 1 year

Pernicious Anemia

Impaired GI absorption of B12

Gastrectomy

Corrosive Injuryof GI mucosa

Fish tape worm: worm siphons off B12

Placebo abuse with B12, especially in elderly patients.


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Folic Acid

Sourcein foodyeast, egg yolk, liver and leafyvegetables

Folic Acid (F.A.) is absorbed in the small intestines.

F.A. is converted to tetrahydrofolate by dihydrofolatereductase.

Folic Acid deficiency (F.A. Deficiency) is also called WillsDisease.

Deficiency may produce megaloblastic anemia; neuraltube defect in fetus.


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Therapeutic Uses of Folic Acid (cont)

3. Ingestion of drugs that interfere with intestinal

absorptionand storage of folic acid.

Mechanism- inhibition of the conjugases that break offfolic acid from its food chelators.

Ex.phenytoin, progestin/estrogens (oral contraceptives)

4. MalabsorptionSprue, Celiac disease, partialgastrectomy.

5. Rheumatoid arthritisincreased folic aciddemand or utilization.

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