Download Iron B12 Folate and Hematopoiesis Anemia: decrease in Hgb and/or

Iron B12 Folate and Hematopoiesis 1
Anemia: decrease in Hgb and/or Hct
MACROCYTIC: Megaloblastic  Abnormal DNA synthesis  large immature cells
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Folic Acid (B9) Deficiency: anemia, NO neurologic symptoms in adults, NTD in infants
Caused by inadeq intake, malabsoprtion (EtOH and phenytoin), or increased requirements
Labs:  MCV,  serum folate,  homocysteine
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B12 Deficiency: anemia, neurologic disorders (paresthesia, loss of proprioception, psychosis)
Caused by inadeq intake, malabsorption (pernicious anemia, loss of gastric acid, loss of ileal receptors)
Labs:  MCV,  serum B12,  homocysteine,  MMA
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Tx with folic acid or B12
MICROCYTIC:
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Iron Deficiency Anemia: microcytic, hypochromic erythrocytes
Decreased iron  decreased heme  decreased Hgb synthesis
Caused by long-standing negative iron balance from increased demand, decreased intake, blood loss
Labs:  serum tranferrin,  ferritin
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Iron: absorbed in the duodenum and jejunum with the help of gastric acid +/- ascorbic acid/Vitamin C
Through heme carrier protein 1 (HCP1) (for heme iron, meat)  most efficiently absorbed form of iron
Through divalent metal transporter (DMT1) (for inorganic Fe2+)
Decreased absorption with PPIs, H2 Blockers, Gastrectomy
Transported as Fe3+ via tranferrin ----- Stored as ferritin in macrophages of liver, spleen, bone, intestinal mucosa
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Tx with iron or erythropoiesis-stimulating agents (ESAs)
NORMOCYTIC (or microcytic):
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Chronic Kidney Dz: Tx with iron or erythropoiesis-stimulating agents (ESAs)
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Anemia of Chronic Disease:  ferritin,  transferrin - Tx with iron (if IDA) or ESAs (not FDA approved
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Myelosuppressive Disorders: anemia, neutropenia, thrombocytopenia
Tx with ESAs, colony-stimulating factors (CSFs), thrombopoiesis-stimulating agents (TSAs)
Iron B12 Folate and Hematopoiesis 2
Drug
Class
Drug Name
MOA
Folic Acid
Folic acid serves as a
single carbon transfer
molecule
Vitamin Replacement
Folate Forms
Supplementation enters
the cycle beyond the
B12 step, potentially
correcting anemias
caused by deficiency of
both folate and B12
However, correction of
the anemia WILL NOT
correct any neurologic
effects if B12 is
deficient
Pharmacokinetics/
dynamics
PO
IV
Indications
AE/DI/CI
Prevention of Folic
Acid Deficiency:
AE:
Rare
Well
absorbed
orally
Pregnancy:
1. to prevent NTD
2. cases with FH or
previous child with
NTD
DI:
Phenytoin (reduces the
absorption of folic acid)
Folic acid also decreases
phenytoin levels
Zero-order kinetics
Base dosing on actual
blood levels of both
phenytoin and folate
because 2x dose does not
equal 2x the concentration
Folic acid =
oxidized
form of
dietary
folates
Alcoholics
Hemolytic Anemia
Megaloblastic Anemia
When Vit B12
Deficiency has been
ruled out!!
Requires
dihydrofolat
e reductase
Folate Antagonists:
Methotrexate
Trimethoprim
Phenobarbital
Pyrimidone
Drugs that cause FAD:
Azathioprine
6-mercaptopurine
5-fluorouracil
Hydroxyurea
Zidovudine
Other
Iron B12 Folate and Hematopoiesis 3
Drug Name
MOA
Folinic Acid
5-formyl derivative of
tetrahydrofolate
Septra-induced
megaloblastic anemia
Converted to
tetrahydrofolate
(but does NOT require
dihydrofolate
reductase)
Methotrexate
chemotherapy
"rescue" agent
Vitamin Replacement
Folate Forms
Drug
Class
Cyanocobalamin is
converted to its active
forms: cobalamin and
methylcobalamin
Indications
AE/DI/CI
Other
Rare
Monitor:
Serum Hgb
Serum B12
Neurologic
Symptoms
Chemotherapy adjunct
(enhance 5-FU)
Therefore,NOT
affected by inhibitors:
Methotrexate
Sulfamethoxazole
Trimethoprim
(Septra)
Vitamin B12
Vitamin Replacement
B12
Pharmacokinet/dyn
NOT used to treat
anemia only
15-20%
absorb
normally
1% can be
absorbed
without IF
Cyanocobalamin
Cyano:
PO;
Nasal, SQ,
IM (avoids
1st pass,
when no IF)
Hydroxocobalamin
Hydrox:
Long-acting
injection
Hydroxy:
Cyanide poisoning
Iron B12 Folate and Hematopoiesis 4
Drug
Class
Drug Name
MOA
Pharmacokinet/dyn
Indications
AE/DI/CI
Other
Iron
Replacement
~25%
absorption
with IDA
Prevention of Iron
Deficiency Anemia in:
premature infants
children
pregnant/lactating
women
heavy menstruation
chronic kidney disease
AE:
GI upset
(nausea, cramping)
( based on amount of
elemental Fe in dose)
Black stools
Monitor:
Fe stores
(prevent Fe
overload)
Iron dextran
IV or IM (staining)
Iron sucrose
Ferrous sulfate
Ferrous gluconate
Ferrous fumarate
Replacement
Iron
Ferymoxytol
$$$$
Ferric
Carboxymaltose
$$$$$
Food
decreases
absorption
PO for most
Treatment of IDA
IV if
severely
depleted
BLACK BOX
WARNING
Test dose for iron
dextran due to
anaphylaxis
DI:
Decreased absorption
with:
Al-, Mg-, Ca++ antacids
Tetracycline/ doxycycline
H2 antagonists
PPIs
Cholestyramine
Acute Iron
Toxicity:
Most
common in
children
Tx with
bowel
irrigation and
iron chelating
agent
Keep iron
supplements
away from
children
Iron B12 Folate and Hematopoiesis 5
Erythropoiesis Stimulating Agents (ESAs)
Drug
Class
Drug Name
MOA
Pharmacokinet/dyn
Indications
AE/DI/CI
Other
Erythropoiesis
Stimulating Agents
Stimulate erythroid
proliferation and
differentiation by acting
on EPO receptor
(JAK/STAT) of RBC
progenitors
IV for
hemodialysis pts
Chronic Kidney
Failure (due to
inability to produce
endogenous EPO)
AE:
HTN
Thrombotic complications
Induction of pure red cell
aplasia (PRCA) - rare
Monitor:
FDA Warning:
 Hgb > 12 g/dL using
EPO is associated with
increased mortality
Hgb monthly
must be
< 12 g/dL
Erythropoietin
(epoetin alfa)
SQ/IV 3x wk
Causes increase in Hct
Darbepoetin
(modified erythropo) and Hgb and reduces the
SQ/IV wkly
need for transfusions
GOAL:
Hgb = 12 g/dL
(low end of normal)
Iron Deficiency
Anemia
Epoetin beta
Banned in the Olympics
Anemia of Chronic
Disease (not FDA
approved)
Myelosuppressive
Anemia
Ferric Citrate
(Auryxia)
Supplements
SQ for
peritoneal
dialysis or
non-dialysis
pts
Sucroferric
oxyhydroxide
(Velphoro)
May reduce iron and
ESA needs over time, by
50 and 25% respectively
Chronic Kidney
Disease with
Hyperphosphatemia
and Iron Deficiency
AE:
Diarrhea
N/V
Iron overload (Auryxia)
Abnormal taste (Velphoro)
Serum Fe (to
support RBC
formation)
Iron B12 Folate and Hematopoiesis 6
Colony Stimulating Facotrs (CSFs)
Drug
Class
Drug Name
MOA
Granulocyte colonystimulating factor
(G-CSF)
Filgrastim
Pegfilgrastim
G-CSF stimulates
proliferation and
differentiation of PMNs
via the G-CSF receptor
on granulocyte
progenitor cells
GranulocyteMacrophage colonystimulating factor
(GM-CSF)
Sargramostim
Thrombopoiesis-Stimulating Agents
(TSAs)
Romiplostim
GM-CSF stimulates the
proliferation and
differentiation of CFUGEMM multipotent
progenitor cells via the
GM-CSF receptor
(less specific, more AE)
Rom: thrombopoietin
receptor agonist
Pharmacokinet/dyn
Indications
AE/DI/CI
Neutropenia (G-CSF)
AE:
Bone pain (both)
Stem cell or bone
marrow transplant
(GM-CSF)
G-CSF:
Splenic rupture - rare
Pts treated with
chemotherapy at risk
for febrile neutropenia
(no evidence for
increased survival, just
lab changes)
GM-CSF:
Fever
Malaise
Arthralgia
Myalgia
Peripheral edema
Pleural/pericardial
effusions
Rom: Tx of Chronic
Thrombocytopenia
Purpura (ITP)
Not 1st Line therapy
AE:
Minimal (rom)
Cardiovascular toxicity
(oprev)
Hepatotoxicity (elt)
Hemorrhage (elt)
Oprelvekin (IL-11)
SQ
IL-11: binds IL-11
receptor stimulating
megakaryocytic
progenitors and
increasing PLT
IL-11: prevention of
chemo-induced
thrombocytopenia
Eltrombopag
Elt: thrombopoietin
receptor agonist
Elt: Refractory ITP
Severe aplastic anemia
Thrombocytopenia with
Hep C
Other