Pharmacology of Anemia and Hematopoietic Growth Factors Flashcards
1
Q
What drugs can be used to treat neutropenia?
A
- Filgrastim
- Pegfilgrastim
- Sargramostim
- Plerixafor
2
Q
What drugs can be used to treat thrombocytopenia?
A
- Oprelvekin
- Romiplastim
- Eltrombopag
3
Q
What is used to treat sickle cell?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
Hydroxyurea
- Boosts levels of fetal hemoglobin
- lowers concentration of HbS
- Only disease modifying therapy for sickle cell
- Administered orally and distributed widely
- Neutropenia, oral ulcers, GI upset
4
Q
What does this show
A
hypochromic microcytic anemia- not enough Hemoglobin
5
Q
What are the 4 causes of microcytic anemia?
A
- Reduced iron availability
- Reduced heme syn. seen in lead poisoning or sideroblastic anemias
- Reduced globin production seen in thalassemias or hemoglobinopathies
- Rare disorders due to irob absorption, transport utilization and recycling defects
6
Q
What can cause iron deficiency?
A
- Inadequate intake
- Malabsorption
- Blood loss
- Increased requirement
7
Q
Describe acute iron toxicity and how to treat it?
A
- Seen in young kids who accidently ingest iron tablets
- Presents with necrotizing gasttoenteritis, with vomiting, abdomen pain and bloody diarrhea.
- leads to shock, lethargy, and dyspnea
- Improvement occurs but then followed by severe metabolic acidosis, coma and death
- Treat with parenteral deferoxamine
- activated charcoal will not bind iron and is ineffective
8
Q
A
Megaloblastic anemia
9
Q
A
macrocytic anemia with hypersegmented neutrophil
10
Q
What happens if the bodies stores of B12 are depleted?
A
- Rapid onset of neuro dysfxn
- paresthesia, weakness and spasticity that may not fully reverse
11
Q
What can cause pernicious anemia?
A
- autoantibody formation that either blocks the IF Cbl interaction or the IF-Cbl receptors in the Ileum preventing absorption
- Chronic atrophic gastritis due to Abs directed against HKATPase of parietal cells
12
Q
What are some symptoms of B12 deficiency?
A
- Hyperpigmentation
- Glossitis
- Anemia macrocytic megaloblastic
- Neutropenia (hypersegmented)
- Thrombocytopenia
- gait issues, cognitive impairment
- paresthesias
13
Q
How to treat B12 deficiency?
A
- Oral B12 is effective even in patients with pernicious anemia as there is an alternative B12 absorption path that doesn’t require IF
- Parenteral therapy is used if neuro symptoms are present
14
Q
What causes folate deficiency?
A
Usually inadequate dietary intake or alcoholism, sometimes malabsorption in jejeunum
15
Q
A
16
Q
Symptoms of folate deficiency?
A
- Neural tube defects in fetus
- Jaundice
- Mouth ulcers
- Anemia macrocytic megaloblastic
- Neutropenia (hypersegemented)
- Thrombocytopenia
- Neuro is very rare (none for exam purposes) but depression rarely
17
Q
Epoetin alfa:
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- Stimulates erythropoiesis
- increases reticulocyte count in less than ten days
- Used in anemia due to CKD or chemo
- Gived IV or subcutaneously
- Increased risk of death, MI, stroke, VTE, tumor progression
18
Q
Eculizumab?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- Monoclonal ab that binds to C5 compliment protein inhibiting clevage to C5a and C5b preventing the MAC complex
- Inhibits terminal compliment mediated intravasscular hemolysis in PNH
- Also inhibits complement mediated thronbotic microangiopathy in patients wiwth atypical hemolytic uremic syndrome
- PNH and atypical hemolytic uremic syndrome, only available under risk eval and mitigation strategy
- Given IV once per week for four weeks and then maintenance doses given every two weeks
- MOST EXPENSIVE DRUG ON MARKET but super effective so insurances pay
- Viral infections, life thretening meningococcal infections, immmunogenic, URI, msk pain, anemia, leukopenia, htn, headache, insomnia, UTI
19
Q
Causes of Neutropenia?
A
- Cancer or other bone marrow damaging diseases
- Congenital DO
- VIral infections
- AI
- overwhelming infections
- Drugs that destroy neutrophils or damage bone marrow
20
Q
Symptoms of neutropenia?
A
- Fever
- Sore mouth
- Odynophagia
- Gingival pain
- Skin absess
- Recurrent sinusitis and otitis
- Pneumonia
- Perirectal pain
21
Q
What type of bacterial infections predominatly causes neutropenic fever?
A
Gram Positive
22
Q
What is neutropenic fever?
A
- Single oral temp of 101 or greater for greater than one hour
- Life threatening complication of chemo
23
Q
What is Filgrastim?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- Recombinant G-CSF
- Regulates production of neutrophils within the bone marrow affecting neutrophil progenitor cells proliferation and differentiation
- Used to decrease incidence of infection from febrile neutropenia in patients with non myeloid malignancies recieveing myelosuppresssive cancer drugs or those recieving a bone marrow transplant
- Given IV or SC
- wait 24 hours after chemo
- Well tolerated but can cause allergic rxn
24
Q
Pegfilgrastim?
A
Longer lasting version of filgrastim due to conjugation with monomethoxypolyethylene glycol
25
Q
Sargramostim?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- Recombinant form of GM-CSF
- increase production of neutrophils eosinophils monocytes and macrophages
- Accelerates recovery of myeloid cells after bone marrow transplant
- can also be used to mobilize hematopoietic stem cells
- used following induction chemotherapy in patients greater than 55 with AML to shorten neutrophil recovery time and decrease infections
- Given IV or SC
- Causes fluid retention resulting in edema, sequestration of granulocytes in puolmonary circuation causing dyspnea, worsened pre existing renal and hepatic dysfunction, contains benzyl alcohol and can cause fatal gasping syndrome in infans
26
Q
Between filgrastim and sargramostim which one has fewer adverse effects?
A
Filgrastim/pegfilgrastim
27
Q
Plerixafor?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- partial agonist of CXCR4 receptor which homes HSC to the bone marrow
- Mobilizes HSC from bone marrow to the plasma
- Used in patients who don’t mobilize sufficient stem cells, it is an “orphan drug” and very expensive, approved for those with lymphoma nad multiple myeloma
- SubQ injection
- Hypersensitivities
28
Q
Oprelvekin (IL-11)?
- MOA
- Effects
- Clinical application
- Pharmacokinetics
- Toxicities
A
- Recombinant IL 11 with an unkonwn MOA, independent of thrombopoietin or its receptor
- Promotes the formation and maturation of megakaryocytes
- Used to treat thrombocytopenia in patients undergoing myelosuppressive chemo for non myeloid cancers
- DOES NOT HAVE MAJOJR CLINICAL USE
- Given Sub!
- SIgnificant edema, cardiac dysrhythmias, severe allergic rxn, blood shot eyes
29
Q
Romiplostim?
MOA
Effects
Clinical application
Pharmacokinetics
Toxicities
A
- Peptibody that binds to the TPO receptor
- has no TPO homology
- Increases the platelet count in healthy individuals and those with ITP and MDS
- Used in those with Idiopathic thrombocytopenic purpura, used after failure of glucocorticoids and Ig’s
- Given subQ
- well tolerated, most serious concern is allergic rxn
30
Q
Eltrombopag?
MOA
Effects
Clinical application
Pharmacokinetics
Toxicities
A
- Non peptide TPO receptor agonist
- Increases platelet count in healthy and those with ITP and cirrhosis due to HepC
- Orally active given once/day
- May cause hepatotoxicity
31
Q
What main drugs cause hemoytic anemia?
A
- Cephalosporins are the most common particularly ceftriaxone and cefotetan
- Penicilins especially piperacillin
- others include, levodopa,NSAIDs, quinidine, methyldopa
32
Q
What are classic causes of non immune drug induced thrombocytopenia?
A
- quinidine and quinine
33
Q
Most common cause of immune drug induced thrombocytopenia?
A
heparin
34
Q
What are the three major drugs/toxins that cuase aplastic anemia?
A
- Cancer chemotherapeutics especially alkylating agens, antimetabolites and cytotoxic abx
- Chloramphenicol
- Benzene
