Pharmacology Treatment of Anemia
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. What would you like to do?
What would be ways of providing non-pharmacologic intervention for anemias?
Identify and manage underlying cause, transfusion support
What are examples of pharmacologic treatments for anemia?
Iron, folate, vitamin B12, Epo
When would you give a RBC transfusion to treat anemia?
- Blood loss is brisk or anticipated
- Symptomatic anemia (hemodynamic instability, cardiorespiratory symptoms)
- Asymptomatic profound anemia (<70g/L)
What are some sources of iron? List them from highest to lowest bioavailability.
Heme (meat products), Fe complexed to organic compounds, Fe salts complexed to inorganic compounds (vitamin supplements)
How is Fe distributed in the body?
2/3 in Hb, 1/2 in storage (in other cells: liver, as cytocomes, etc.)
True or false: Metabolic and storage pool iron is primarily regulated by absorption. Normal iron loss is small.
True; Males lost 1mg/day, females: 2mg/day
What part of the intestine is Fe primarily absorbed at?
Duodenum or proximal jejunum
What is the average intake of iron/day and how much of that is absorbed?
Average intake: 10-15 mg elemental Fe/day, 10% absorbed or 1mg/day
What are the conditions that require increased intake of Fe?
Menstruation, pregnancy, rapid growth, blood loss
What are the factors that affect absorption and bioavailability of iron?
- Form of iron,
- Acid environment of stomach/vitamin C presence (may help with Fe absorption) and
- Chelators (reduce absorption)
How is heme iron absorbed? What can non heme iron be bound to to reduce availability? What form of Fe are iron salts converted to before absorption?
- Heme is absorbed as intact Hemin
- Non-heme Fe may be bound to phytates, reducing availability
- Fe salts are converted to ferrous salts (Fe+2) before absorption
What are the 3 types of oral iron supplements and how much iron does each contain?
- Ferrous gluconate: 30-36 mg elemental Fe
- Ferrous sulphate: 60-66 mg elemental Fe
- Ferrous fumarate: 90-100 mg elemental Fe
After starting oral Fe, how long does it take to see an increase in Hb? how long does it take to correct anemia?
2-4 weeks to increase Hb. May take up to 3 months to correct anemia. Replenish stores of Fe within 3-6 months after normalization of Hb.
What are some potential side effect of oral iron? Are they dose related?
- Side effects are usually in the GI tract: nausea, epigastric abdominal pain, constipation/diarrhea. Overdose can be lethal.
- Yes, the side effects are dose related
When do you put a patient on parenteral (IV) iron instead of oral?
Patients who cannot tolerate oral Fe or cannot absorb Fe adequately. And/or when losses are greater than what oral iron can provide.
When there is a deficiency in vitamin B12 or folic acid, what stage of the cell cycle are cells arrested in?
What cells are most effected by vitamin B12 and folic acid deficiencies?
- Rapidly dividing cells, specifically:
- - Hematologic cells: megaloblasts (large erythroid precursors with large nuclei and open chromatin, but cytoplasm of mature cell)
- - Non-hematopoietic cells: GI epithelium
True or false: folate deficiency affects neurologic tissue
False: only vitamin B12 deficiency affects neurologic tissue
What are some sources of B12?
Bacterial synthesis (not made by plants or animals). Get it in diet through animals, fish, eggs, dairy products, nitrogen fixing bacteria in legumes
How much vitamin B12 do you need in a day?
How long of a supply of vitamin B12 do you have in your liver?
3-5 years supply
What are the steps in vitamin B12 absorption?
- Stomach: Acidic pH frees B12 from nonspecific binding to dietary protein, parietal cells release intrinsic factor (IF), and free B12 binds R protein present in salvia/gastric secretions
- Duodenum: pancreatic protease in alkaline environment digest R protein, releasing B12, which then binds IF
- Terminal Ileum: B12 + IF binds to IF receptors on mucosal cells
What are some dietary sources of folic acid?
Green leafy vegetables, yeast, animal tissue, synthesized microbes
How much folate is required in a daily diet? How long of a store do you have in your liver? How it is lost?
- At least 50 ug/day requirement
- Stores: only 3-4 months (liver)
- Loss: urine/stool, catabolism
What is the process of folic acid absorption?
Ingested as polyglutamates. In jejunum (brush border), it is hydrolyzed to monoglutamates that bind folate binding protein in the brush border. It is then reduced and methylated in mucosal cells to become methyl-tetrahydrofolate (THF). Free methyl-THF is released into the palsma and can bind cell receptors on endocytic vesicles and may be converted back to polyglutamates.
What is the primary role of B12/folate in cells?
Transfer of single carbon units from folate molecule to participate in variety of metabolic pathways
What parts of DNA synthesis is folic acid involved in?
Purine synthesis and Thymidylic acid synthesis (dUMP -> dTMP)
How does vitamin B12 deficiency lead to neurologic toxicity?
Demyelination of peripheral nerves, posterior column and CNS; Accumulation of MMA may also contribute
How does vitamin B12 contribute to folic acid deficiency?
Through the folate trap -> without vitamin B12, you are unable to recycle folate, leading to impaired DNA synthesis and megaloblastic anemia
True or false: Neurologic symptoms in B12 deficiencies can occur in the absence of megaloblastic anemia.
True or false: folic acid supplementation can correct megaloblastic anemia from decreased B12 but not neurologic abnormalities.
What are some symptoms of vitamin B12 deficiency?
Neurologic abnormalities: glove/stocking numbness, decrease vibration/position sense, memory loss
How do you treat vitamin B12 deficiency?
- Parenteral B12 for malabsorption
- Cobalamin intramuscular injections daily x1-2 weeks to replenish stores, then monthly for life
- Large doses of oral B12 may also work
How quickly will vitamin B12 treatment start to work?
Expect rapid hematologic response (within 48 hours). But neurologic improvement will be slower.
How do you treat folic acid deficiency?
- Oral supplementation daily for deficiency states
- Supplementation recommended for patients with rapid RBC turnover e.g. autoimmune hemolytic anemia
What does the kidney control through EPO?
Important aspects of oxygen delivery including blood volume, blood pressure and red cell mass
True or false: exogenous administration of EPO generally fails to boost hemoglobin levels
False: Exogenous administration of EPO (EPO injections) can boost hemoglobin levels
When do you give EPO to patients?
- Chronic renal failure (EPO deficiency)
- Anemia in patients with AIDS on antivirals
- Anemia associated with chemotherapy for malignancies
- Peroperative management to avoid blood transfusions (boost preoperative Hb)
- Myelodysplastic syndrome (MDS) to reduce transfusion requirements
What are some common, but unlikely, side effects of EPO given in low doses?
Hypertension and thrombosis (due to rapid increase in Hb)
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