Pharmacology of Anemia and Hematopoietic Growth Factors

Question 1

What are some causes of microcytic anemia?

What is the MCV?

Answer 1

Reduced iron availability (most common)
Reduced heme synthesis
Reduced globin production

MCV < 80 fL

Question 2

What are some side-effects of oral iron supplementation?

Answer 2

Nausea, constipation, anorexia, heartburn, vomiting, diarrhea and dark stools.

Question 3

What is the dosage and frequency for oral iron?

Answer 3

200-400 mg of ferrous iron 2-3x/day.

Question 4

What form of iron is used in supplementation/treatment?

Answer 4

Ferrous iron (2+)

Question 5

Under what conditions would parenteral iron be preferred to oral iron?

Answer 5

If the patient has iron malabsorption, is intolerant of oral therapy, is non-compliant, etc.

Question 6

What symptoms would be observed in acute vs. chronic iron toxicity?

Answer 6

Acute: severe GI symptoms which can lead to shock and dyspnea. The child may appear to be improving, however, they still may progress to severe metabolic acidosis, coma and death.
It is almost always seen in children.

Chronic: hemochromatosis - iron deposits in the heart, liver, pancreas, etc. which leads to organ failure and death.

Question 7

What is the indication for parenteral Deferoxamine?

Answer 7

Acute iron toxicity; whole bowel irrigation is also indicated.

Question 8

What inactivated cyanocobalamin (a form of vitamin B12) during anesthesia?

Answer 8

Nitrous oxide

Question 9

What is the treatment for vitamin B12 deficiency (megaloblastic anemia and pernicious anemia)?

How does this change if neurological symptoms are present?

Answer 9

Oral vitamin B12 supplementation.

Parenteral therapy is indicated if neurological symptoms are apparent.

Question 10

What side-effect can occur with high dosage of folate?

Answer 10

Hypotension and hypoglycemia

Question 11

What happens if the body stores of vitamin B12 are depleted?

Answer 11

There is rapid onset of neurological dysfunction that may not fully reverse.

Question 12

How quickly do symptoms improve after treatment for megaloblastic anemia (folate vs. B12 treatment)?

How does this change if neurological symptoms are observed?

Answer 12

Typically they improve in a few days.

• Hct increases in < 2 weeks with folate therapy and normalizes in about 2 mo.
• Hb increases with 1 week of vitamin B12 therapy and should normalize in 1-2 mo.

If neurological symptoms are observed, it will take longer to improve and may not be reversible.

Question 13

Epoetin alfa MOA:

Indication:

Adverse-effect(s):

Answer 13

MOA: erythropoiesis-stimulating glycoprotein (stimulated erythropoiesis).

Indication: anemia due to chronic disease (CKD).

Adverse-effect(s): diastolic arterial pressure > 10 mmHg despite a Hct in 30-35% range.

Question 14

Hydroxyurea MOA:

Indication:

Adverse-effect(s):

Answer 14

MOA: targets ribonucleotide reductase and results in S-phase arrest. This lowers the [HbS] in the cell.

Indication: SSD - the only disease-modifying therapy for SSD.

Adverse-effect(s): cough, fever, chills, LBP, painful urination.

Question 15

Eculizumab MOA:

Indication:

Adverse-effect(s):

Answer 15

MOA: inhibits terminal complement-mediated intravascular hemolysis (binds C5 protein and prevents its cleavage).

Indication: paroxysmal nocturnal hemoglobinuria.

Adverse-effect(s): many - mostly infection (URI, HSV, flu, meningitis).

Question 16

Filgrastim MOA:

Indication:

Adverse-effect(s):

Answer 16

MOA: it is a synthetic G-CSF.

Indication: neutropenia.

Adverse-effect(s): allergic reactions (generally well-tolerated).

Question 17

What is the difference in Filgrastim and Sargramostin?

Which one has fever adverse-effects?

Answer 17

Filgrastim is a synthetic G-CSF.
Sargramostim is a synthetic GM-CSF.

Filgrastim.

Question 18

Plerixafor MOA:

Indication:

Adverse-effect(s):

Answer 18

MOA: partial agonist of CXCR4 receptor. This mobilizes HSCs from BM to plasma.

Indication: conditions where HSC mobilization is poor; also for lymphoma and MM.

Adverse-effect(s): hypersensitive reactions.

Question 19

Oprelvekin MOA:

Indication:

Adverse-effect(s):

Answer 19

MOA: recombinant for of IL-11 which increases platelet levels by promoting megakaryocyte maturation.

Indication: thrombocytopenia in patients undergoing myelosuppressive chemotherapy for non-myeloid cancers, but it does not have a major clinical use.

Adverse-effect(s): edema due to volume expansion, cardiac dysrhythmias and bloodshot eyes.

Question 20

What is the only orally available TPO receptor agonist?

Answer 20

Eltrombopag

Question 21

What is the 1st-line therapy for ITP?

What are 2nd/3rd-line treatments?

Answer 21

1st: splenectomy.

2nd/3rd: Romiplostim and Eltrombopag.
-they should be used if a splenectomy is contraindicated and/or rituximab did not work.

Question 22

What drugs most commonly cause hemolytic anemia? (2)

Answer 22

Cephalosporin antibiotics: ceftriaxone and cefotetan.

Piperacillin may also cause it.

Question 23

What drug causes immune drug-induced thrombocytopenia?

What drugs cause non-immune drug-induced thrombocytopenia?

Answer 23

Heparin

Quinidine and quinine.

Question 24

What can cause aplastic anemia? (3)

Answer 24

Cancer chemotherapies (esp. alkylation agents and cytotoxic antibiotics).

Chloramphenicol - antibiotic that is no longer used.

Benzene

Question 25

What is the only disease-modifying therapy for SSD?

Answer 25

Hydroxyurea

Question 26

What is the only drug indicated for PNH?

Answer 26

Eculizumab

Question 27

What drug “does not have a major clinical use”?

Answer 27

Oprelvekin