agents of anemia Flashcards
oral route of iron therapy- drugs ? how long ? what enhances it ?
Ferrous iron Fe2+ is best absorbed:
• Ferrous sulfate
• Ferrous gluconate
• Ferrous fumarate
Treat for 3-6 months after correction of the cause .
Ascorbic acid co-administered for optimal
absorption.
parenteral route for iron absorption - PK ? drugs ? who do you give it to ?
• Chronic renal failure patients have a high iron
requirement.
• Parenteral iron is given to hemodialysis patients (in
combination with erythropoietin).
> also for people who dont respond to oral iron therapy
• Iron dextran – highest risk of type I
hypersensitivity reaction
• Sodium ferric gluconate complex
• Iron sucrose
AE of iron therapy
• Black stools • GI upset: • Nausea • Epigastric discomfort • Abdominal cramps • Constipation • Diarrhea --> can confound results of gastrointestinal bleeding
acute iron toxicity effects on body ?
- Direct GI tract irritation:
- acute vomiting
- diarrhea
- abdominal pain
- mucosal ulceration and bleeding
pathogenesis of acute iron toxicity
• Free iron disrupts critical cellular processes, resulting in: • Metabolic acidosis. • Widespread organ toxicity which can progress to shock, coma then death.
acute iron toxicity dignosis
• Historical suspicion of ingestion.
• Abdominal radiographs often demonstrate
radio-opaque pills in the stomach.
Acute Iron Toxicity - Treatment
• Note that activated charcoal is ineffective as
it does not bind iron.
• Treatment includes supportive care and iron
chelators
Deferoxamine
• Given IV to bind systemic iron.
• Promotes iron excretion in urine and feces.
• Indicated in moderate to severe iron toxicity.
Deferasirox
• Oral preparation.
• Only effective at reducing iron absorption if
given within one hour of iron ingestion.
when does Chronic Iron Toxicity occur ? pro oxidant effect ? treatment ?
in • Inherited hemochromatosis and patients requiring
frequent blood transfusions (e.g. thalassemia
major).
Pro-oxidant effect:
• Cardiomyopathy
• Cirrhosis
• “Bronze Diabetes”
Chronic Iron Toxicity Treatment
Deferasirox –> Outpatient iron chelation in transfusion
dependent individuals.
for patients who dont require transfusions –> treatment is simple phlebotomy
Vitamin B12 Deficiency Causes
- Insufficient ingestion :
- Vegan diet without B12 supplementation.
Defects in absorption of cobalamin : • Autoimmune disease – Pernicious anemia • Surgery – gastrectomy, ileal resection • Small bowel disease – Crohn’s, Coeliac disease, fish tapeworm infestation
Drugs inhibiting absorption of B12:
• metformin, neomycin – alter gut microflora
• nitrous oxide anesthesia – converts
cob(I)alamin to the inactive form cob(III)alamin
• proton pump inhibitors, histamine 2 receptor
antagonists – increase gastric pH
Vitamin B12 Deficiency Presentation
Neurologic changes:
• Paresthesias in early disease.
• Subacute Combined Degeneration (SCD) of the
spinal cord due to abnormal myelin synthesis.
• Prolonged deficiency = irreversible nerve damage.
Skeletal changes
• Suppression of osteoblast activity may lead to
an increased risk of osteoporosis.
Vitamin B12 Deficiency Lab Studies
- CBC & Peripheral Blood Smear
- Megalobastic, macro-ovalocytotic anemia
- Leukopenia and/or thrombocytopenia.
Serum vitamin B12 levels
• Reduced
Antibodies against intrinsic factor
• Positive in in pernicious anemia
Serum homocysteine
• Increased
Serum methylmalonate
• Increased
- Serum methylmalonyl-CoA levels
- Increased
Folate Deficiency Risk Factors
• Advanced age
• Pregnancy
• Chronic hemolytic anemias eg. sickle cell anemia
• Alcohol abuse
• Impairs the enterohepatic circulation of folate within
four days and can lead to megaloblastosis within 5 to 10 weeks
folate deficiency causes
methotrexate
phenytoin
trimethoprim
pyrimethamine
Folate Deficiency Presentation
• Clinical features of anemia.
• No neurological signs or symptoms in contrast with
cobalamin deficiency.
• Fetal neural tube defects in the first trimester of
pregnancy.
Folate Deficiency Lab Studies
CBC & Peripheral Blood Smear
• Macrocytic, megaloblastic anemia
Serum/ red cell folate levels
• Decreased
Serum homocysteine level
• Increased
Serum methylmalonate levels
• Normal
Folate Therapy
• Folic acid given orally for 1– 4 months or
until complete hematological recovery
occurs
Should NEVER be initiated in isolation in persons
with a macrocytic, megaloblastic anemia.
• Both hydroxocobalamin and folic acid should be
started until serum assays of methylmalonate are
available to determine whether vitamin B12
deficiency is present
Prophylactic supplementation should be given to persons with the following risk factors : • Pregnancy • Alcohol dependence • Hemolytic anemia 52 • Liver disease • Exfoliative skin disease • Renal dialysis
erythrocyte growth factors ? PK? PD? AE
derbepoetin - ocne a week
erythropoeitin (epoetin alfa)-IV- 3 times a week
they both act via JAK/STAT receptor binding leading to 1) stimulation of erythroid proliferation and differentation
2) induction of reticulocyte release from bone marrow
given to pateints with chronic renal failure and bone marrow suppression
AE–> HTN, thrombosis
Myeloid growth factors
filgrastim (G-CSF)
Sargramostim (GM-CSF)
for cancer chemotherapy nutropenia and bone marrow suppression
AE–> bone pain but filgrastim is better tolerated
megakaryocyte growth factor ?
interleukin 11
acts via cell surface cytokine receptor
stimulate the growth of primitive megakaryocyte progenitors
incres count of peripheral platelets and neurtophils
reduces the need fro platelet transfusion in chemotherapy recipients with prior episodes of thrombocytopenia
treatment for Sickle cell
hydroxyurea
increases HbF
decre expression of neutropihl adhesion molecule
increases production of endothelial NO
