Flashcards in Anti-Anemia Drugs Deck (38):
What are the 3 "nutritional amenias"?
1. Folate (folic acid)
What are the 5 mechanisms by which nutritional anemias arise?
The deficiencies arise from:
1. inadequate ingestion
2. improper absorption or utilization
3. increased requirement
5. metabolic destruction of the nutrient
Describe the CBC of Fe deficiency anemia.
microcytic and hypochromic due to a reduction in Hb synthesis
80% of the Fe in the body is involved in _________________ but the rest are essential components for what?
80% is involved in RBC synthesis, but the rest is used in enzymes and proteins like:
4. xanthine oxidase
5. a-glycerophosphate oxidase
This is what causes the lethargy and weakness associated with Fe deficient anemia
What are the 3 major causes of Fe deficiency?
1. Bleeding- for men GI is most common, for women GU (menses) or GI
2. Inadequate dietary intake
3. Interference with Fe absorption- usually after surgery where duodenum/jejunum is removed or with tropical sprue (flattening of villi and inflammation of the colon)
Who is at an increased risk of Fe deficiency in developed countries?
Pregnant women because there is increased demand for the growing fetus and maternal tissues.
Complete ferritin depletion is seen in 2nd and 3rd trimesters
Oral Fe preparations are usually __________ because they are more easily absorbable but they must be converted to __________ in the body to be usable.
Ferrous salts (Fe2) like sulfate, gluconate, fumarate
but must be converted to ferric iron (Fe3) in the body
What are the oral preparations of ferrous salts?
Parenteral Fe preparations contain _____________ .
Ferric iron complexed to a carbohydrate.
1. iron dextran
2. sodium ferric gluconate
3. iron sucrose
What are 3 examples of parenteral preparations of iron?
Which can cause anaphylaxis and allergic reaction?
Which can cause renal damage?
Which is the preferred preparation?
1. Iron dextran - anaphylaxis and allergy
2. Na ferric gluconate -preferred
3. Fe sucrose - renal damage
How much better are ferrous salts absorbed than ferric salts?
What is frequently given with oral Fe to preserve the salts and assist in absorption?
Ferrous salts absorb 3x more rapidly than ferric.
Vitamin C is given orally to preserve ferrous salts in ferrous form so they are absorbed
How long does it take to replenish Fe stores from oral iron?
Up to 6 months even if it is given at a dose 20x higher than normal daily intake
What preparation of Fe is chosen if you need to build iron stores rapidly?
IV parenteral Fe with a dose of 1200-2000mg
Iron dextran can replenish in one dose but it can cause allergic rxn and anaphylaxis
What are the side effects of oral Fe preparations?
What can reduce these side effects?
heartburn, nausea, upper GI discomfort, constipation and/or diarrhea
Side effects can be reduced by using Fe-polysaccharide complexes
Why must you be careful when giving Fe to children?
Large doses of ferrous salts can be toxic and cause death in children
What drug is given for Fe poison?
How is it given and by what mechanism does it work?
Deferoxamine is given IM or IV and chelates the Fe
What are the side effects of iron dextran?
How is it administered?
Allergic reactions and anaphylaxis
It is administered IV bc IM or SC preparations increase the risk of anaphylaxis and also cause severe skin staining
What is the major side effect of Iron sucrose?
It can causes renal damage
In what situations would you choose an oral preparation for Fe deficiency?
In what situations would you choose parenteral?
1. bleeding, inadequate diet, pregnancy
1. rapid restoration of Fe for SEVERE deficiency
2. when oral Fe can't be tolerated
3. when it can't be absorbed (after duodenal/jejunum surgery or tropical sprue)
What is the most common form of vit B12 deficiency?
Pernicious anemia- caused by the absence of intrinsic factor which is necessary for absorption of B12
A deficiency in ______ leads to megaloblastic anemia more rapidly than a deficiency in _______ because ___________________.
The body stores of folate are more limited than the stores of B12.
It takes weeks to deplete folate and months to deplete B12
What are the three major causes of pernicious anemia?
1. atrophy of the gastric mucousa
2. Autoantibodies against parietal cells
3. autoantibodies against Intrinsic Factor
In addition to pernicious anemia, what else can cause B12 deficiency?
1. gastric surgery (where IF is made)
2. Ileal surgery (where IF and B12 are absorbed)
What are the two stable forms of B12 that can be used as drugs?
What is pharmokinetically different between the 2 drugs?
What are they converted to in the body?
1. Cyanocobalamin (CN+B12)- it is absorbed IM once a month
2. Hydroxycobalamin (OH+B12) - it is depleted more slowly so it can be given IM once every 1-3 months
In the body they are converted to CH3-B12 (methylcobalamin) or 5-deoxyadenosylcobalamin. These can accept CH3 groups from methyl-tetrahydrofolic acid which then allows the demethylated tetrahydrofolic acid to participate in DNA synthesis.
The CH3-B12 and 5deoxyadenosylB12 can then donate methyl group to homocysteine to make methionine which helps maintain the myelin sheath around nerves
What specific aspect of B12 deficiencies do cyanocobalamin and hydroxycobalamin aim to treat?
Neuropathies caused by deficiency of downstream metabolites of B12 like S-adenosylmethionine which maintains the myelin sheath around nerves
What two preparations are used as maintenance doses for treating B12 deficiencies?
Intranasal and sublingual preparations which provide B12 that can be stored in the liver. Enterohepatic circulation ensures constant B12 availability
What are the adverse effects of using cyanocobalamin and hydroxycobalamin?
None really. If given IV instead of IM it can cause anaphylaxis but this is rare
Why are oral preparations no used to administer CN-B12 or B12-OH?
the problem with B12 deficiency is usually malabsorption so they would not be absorbed.
Give the drugs in a LARGE IM dose (loading) and then follow up with 1mg a month maintenance.
What are the 4 most common causes of folate deficiency?
1. pregnancy (due to increased demand)
2. tropical sprue (decreases absorption)
3. acute/chronic alcoholism (decreased intake)
4. drug-induced folate deficiency (methotrexate or Bactrim..they have folate but the enzyme is inhibited so it can't be utilized)
Describe the mechanism by which folic acid is absorbed and converted to a form that participates in DNA synthesis.
1. Folic acid is converted to methyltetrahydrofolic acid in the GI tract.
2. Methyltetrahydrofolic acid gets absorbed into the blood
3. In tissue, it is converted to THF acid and the methyl group is donated to B12
4. THF can participate in DNA synthesis
What are the pharmokinetics of folic acid?
1. how is it administered
2. where is it stored in the body
Oral preparation is preferred, but parenteral can be given in malabsorption issues (like sprue)
Folic acid is stored in the liver
Why must you be certain whether you are dealing with a B12 deficiency or folic acid deficiency?
If there is uncertainty over which is deficient, what should the treatment be?
folate therapy can mask the hematological changes seen with B12 deficiency and allow the advancement of neurological disorder
Give both hydroxycobalamin and folic acid parenterally
What protein regulates the proliferation of commited RBC progenitors (BFU-E and CFU-E)?
What two forms can it be present in?
Where is it secreted?
Erythropoietin (epo) can be present in alpha and beta forms.
It is secreted by the peritubular cells in the kidney
What are 3 causes of inadequate erythropoiesis due to the decreased production of epo?
1. chronic renal impairment
2. cancer patients on chemo
3. HIV patients on AZT
What are the 3 erythropoetins and how do they differ pharmokinetically?
1. epoetin alfa- SC 1 to 3x a week
2.darbepoetin alfa- longer t1/2 so SC every 1to3 wks
3. methoxy polyethelene glycol-epoetin beta (CERA) is administered once a month
What level of Hb are erythropoietin drugs attempting to achieve?
Hb of 10-12g/dL
higher Hb levels carry a risk of thromboembolic events
What are the adverse effects of epo drugs?
1. Due to the rapid increase in Hct, hypertension can be seen in 20-30% of patients
2. Hb above 12g/dL --> thromboembolism
3. accelerated tumor growth and relapse