Anemia Pharm Flashcards
What molecules make up heme?
protoporphyrin IX and Fe
Causes of microcytic anemia
reduced iron availability, reduced heme synthesis, reduced globin production, rare disorders
Foods from which iron is easily absorbed
meat, fish, poultry
How does food effect iron absorption?
inhibits absorption
Side effects of oral iron tablets
nausea, constipation, anorexia, heartburn, vomiting, diarrhea, dark stools
IV iron complexes
iron dextran, sodium ferric gluconate, iron-sucrose
Acute iron toxicity
lethal in young children; sxs include necrotizing gastroenteritis with vomiting, abd pain, bloody diarrhea
Treatment of acute iron toxicity
parenteral deferoxamine, and whole bowel irrigation
Chronic iron toxicity
iron deposits in heart, liver, pancreas and causes organ failure and death
Sources of vitamin B12
fish, meat, poultry, eggs, milk, milk products, fortified breakfast cereals
How long does it take to develop a vitamin B12 deficiency?
years, liver stores a significant amount
Neurological sxs of B12 deficiency
paresthesias, weakness, spasticity
How is cobalamin released from food
acid and pepsin
Causes of pernicious anemia
ab formation blocking IF interaction with cobalamin, chronic atrophic gastritis, gastrectomy, H. pylori infection
Sxs of B12 deficiency
vitiligo, hyperpigmentation, glossitis, anemia, neutropenia, thrombocytopenia
Treatment of vitamin B12 dficiency
oral B12, initially 1-2mg/day for 2 weeks, then 1mg daily; parental therapy if neuro sxs are present
Sources of folate
yeast, liver, kidney, green leafy vegetables
Where is folate absorbed in the body?
jejunum
How long does it take to develop a folate deficiency?
three weeks without adequate intake
Sxs of folate deficiency
neural tube defect in fetus, jaundice, mouth ulcers, anemia, neutropenia, thrombocytopenia, depression
Treatment of folate deficiency
oral folate, 1mg/day for 4 months
epoetin alfa MOA
contains a.a. sequence of isolated erythropoeitin
epoeitn alfa effects
stimulates erythropoiesis, increase rtc in 10 days, increase RBC 2-6 weeks
Clinical applications epoetin alfa
chronic kidney disease, CA chemo
Pharmacokinetics of epoetin alfa
IV or subcutaneously; t1/2 = 4-13 hrs
Epoetin alfa toxicities
increased risk of death, MI, stroke, VTE, tumor progressoin
Hydroxyurea MOA
boosts level of hgb
Effects of hydroxyurea
lowers concentration of HbS within a cell
Clinical applications hydroxyurea
sickle cell
Pharmacokinetics hydroxyurea
administered orally, distributed widely
Toxicities hydroxyurea
neutropenia, anemia, oral ulcers, mild GI upset, hyperpigmentation, rash, nail changes
Eculizumab MOA
mab binds to C5, inhibits cleavage, preventing generation of complement complex
Eculizumab effects
inhibits terminal complement mediated intravascular hemolysis, inhibits complement mediated thrombotic microangiopathy
Clinical applications eculizumab
PNH, atypical HUS
Pharmacokinetics eculizumab
IV over 35 min oncer per week for 4 weeks, maintenance doses given IV every 2 weeks
Toxicities of eculizumab
viral infections, life-threatening meningococal infections, immunogenic, URI, msk pain, anemia, leukopenia, HTN, HA
Causes of neutropenia
cancer, congenital disorders, viral infections, autoimmune disorders, overwhelming infections, drugs
Sxs of neutropenia
low-grade fever, sore mouth, odynophagia, gingival pain and swelling, skin abscesses, recurrent sinusitis and otitis, sxs of pneumonia, perirectal pain and irritation
Filgrastim MOA
human G-CSF
Filgrastim effects
regulates production of neutrophils within bone marrow
Clinical applications filgrastim
decrease incidence of infection in pts with nonmyeloid malignancies receiving myelosuppressive anticancer drugs or those receiving bone marrow transplant, mobilize hematopoietic progenitor cells
Pharmacokinetics filgrastim
IV infusion or continuous SC infusion, wait 24 hrs after chemo, dividing cells most vulnerable
Filgrastim toxicities
allergic rxn, bone pain
sargramostim MOA
recombinant form of GM-CSF
Effects sargramostim
increase production neutrophils, eosinophils, monocytes and macrophages
Clinical applications sargramostim
accelerate recovery myeloid cells after autologous bone marrow transplant, mobilize hematopoietic stem cells, used after chemo induction in pts with AML
Pharmacokinetics sargramostim
given IV or SC
Toxicities sargramostim
edema, sequestration of granulocytes in pulm circulation causing dyspnea, worsened pre-existing renal and hepatic dysfx, can cause fatal gasping syndrome
Does filgrastim or sargramostim have fewer side effects?
filgrastim
UpToDate recommendations on CSF use in CA
no role in afebrile patients, primary prophylaxis if incidence of febrile neutropenia is >20%, secondary prophylaxis if it would reduce efficacy of chemo
Plerixafor MOA
partial agonist of CXCR4 receptor, homing to HSC
Plerixafor effects
mobilizes HSC to plasma
Plerixafor clinical use
used in pts who do not mobilize sufficient stem cells for transplant with just G-CSF
Plerixafor pharmacokinetics
subcutaneous injection, 3-5 hr half life
Toxicities plerixafor
hypersensitivity rxn
Oprelvekin MOA
IL-11
Effects oprelvekin
promote formation and maturation of megakaryocytes
Clinical applications oprelvekin
can be used to treat thrombocytopenia in pts undergoing myelosuppressive chemo for non-myeloid CA
Pharmacokinetics oprelvekin
given SC once/day, half life 7 hrs
Toxicities oprelvekin
significant edema, cardiac dysrhythmias, severe allergic rxn, bloodshot eyes
Romiplostim MOA
binds to TPO receptor
Romiplostim effects
increase plt count in healthy individuals, people with ITP, or those with myelodisplastic syndrome
Romiplostim clinical applications
ITP, after failure of glucocorticoids
Pharmacokinetics romiplostim
administered weekly as a SC injection, half life 3.4 days
Toxicity romiplostim
well-tolerated, but may have allergic rxn
Eltrombopag MOA
non-peptide TPO receptor agonist
Eltrombopag effects
increase plt ct
Clinical applications eltrombopag
excess plt destruction due to ITP, cirrhosis due to hepatitis C
Pharmacokinetics eltrombopag
orally active, given once/day, half life 21-36 hrs
Toxicity eltrombopag
hepatotoxicity
