RHS22 - Agents Used in Anemias Flashcards
C
What Hb levels are considered to be anemic in males and females?
Males - Hb < 13.5 g/dL
Females - Hc < 12.0 g/dL
What is the preferred route of administration from iron replacement therapy? Which drugs are given? How long is treatment usually for?
- Oral route
- Ferrous iron (Fe2+) is best absorbed
- Ferrous sulfate
- Ferrous gluconate
- Ferrous fumarate
- Give with ascorbic acid (Vit C) for optimal absorption. It helps keep the iron in the ferrous form
- Treat until CBC values stabilize. Normally 3-6 months
When and how is iron therapy administered parenterally?
- Parenteral iron is usually given to chronic renal failure patients and hemodialysis patients because they usually have a high iron requirement
- Iron dextran - highest risk of allergic reaction
- Sodium ferric gluconate complex
- Iron sucrose
What are the AE’s of iron therapy? Whats the pathogenesis?
- Black Stools
- GI Upset
- Nausea
- Abdominal discomfort
- Diarrhea
- Constipation
Free iron disrupts critical cellular processes resulting in metabolic acidosis and widespread organ toxicity which can progress to shock, coma, and death
How is acute iron toxicity usually diagnosed and treated?
- Diagnosis based upon suspicion of ingestion and an abdominal radiograph showing radio-opaque pills in the stomach (see image)
Iron chelators are used to treat
- Deferoxamine - given IV to bind iron. Also promotes iron excretion
- Deferasirox - given orally and only effective at reducing iron absorption if given within one hour of ingestion
What are the typical causes of chronic iron toxicity? What is its pathogenesis and how is it treated?
Inhertited hemochromatosis or frequent blood transufions (e.g. - thalassemia major)
The excess iron has a pro-oxidant effect leading to damage of the:
- Heart - cardiomyopathy
- Liver - cirrhosis
- Pancreas - bronze diabetes
Treated with deferasirox
Where is the majority of Vitamin B 12 stored in the body? How long does it take to deplete Vitamin B12 stores?
Majority of B12 is stored in the liver
It takes about 5 years to deplete B12 stores after absorption ceases
List and describe the purpose of the primary reactions cobalamin (B12) is needed for.
- Adenosylcobalamin is required for methylmalonyl mutase to convert methylmalonyl-CoA to Succinyl-CoA.
- Important for the TCA cycle and myelin & heme synthesis
- Dietary folate is in the form methyl-THF. Cobalamin is used to convert it into regular THF. The resulting methylcobalamin is then used by homocysteine methyltransferase (aka - methionine synthase) to convert homocysteine into methionine
- THF is needed for DNA synthesis
- Methionine is important for protein synthesis and provides a methyl group for anabolic reactions
List the drugs that inhibit cobalamin absorption and describe how they do this.
- Metformin & Neomycin - alter gut microflora
- Nitrous oxide anesthesia - converts cobalamin-I to the inactive cobalamin-III
- Proton pump inhibitors and histamine 2 receptor antagonists - increase gastric pH
What are the drugs used to treat cobalamin deficiencies? What is the route of administration? How long does therapy usually last? What are the adverse effects?
Therapy is given parenterally and continues for the duration of malabsorption. There are no known AEs. The preparations used are:
- Hydroxocobalamin (preferred)
- Cyanocobalamin
List the reactions for which THF (folate) is required.
- De novo purine synthesis
- Conversion of dUMP to dTMP
List the drugs that can cause folate deficiency and explain how.
- Trimethoprim, Pyrimethamine, & Methotrexate all inhibit DHF reductase, an enzyme that converts DHF to THF
- Phenytoin - reduces serum folate (mechanism unknown)
Which individuals should receive prophylactic folate therapy?
- Pregnancy
- Alcohol dependence
- Hemolytic anemia
- Liver disease
- Exfoliative skin disease
- Renal dialysis
B
Folic acid should never be given alone until you’re certain the patient only has a THF deficiency. This is because folate will mask the symptoms of the B12 deficiency but won’t prevent the neurological damage caused by it.
