Sweatman Drugs to treat Anemia Flashcards
erythrocyte factors
B12
folate
ESA’s
granulocyte factors
Sargramostatin GM-CSF
Filgrastim G-CSF
Thrombocyte factors
IL-11 (Oprelvekin)
stimulates production of neutrophils specifically
Filgrastim–>G-CSF
stimulates all granulocytes
GM-CSF–> Sargramastin
seondary hemochromatosis is common in
beta thal
Megaloblastic anemia due to
B12 or folate
microcytic anemia
IDA
ACD
Sideroblastic anemia
Thalassemia
cause of pernicious anemia
defect in synthesis of Intrinsic factor to where you can’t absorb b12
- either anti-parietal or anti IF ab’s
- or surgical gastrectomy
regulation of totaly body iron is through
modulation of intestinal (duodenal) absorption HEPCIDIN
*no real good way to get rid of iron
only indication for iron administration
prevention or tx of Iron Deficiency Anemia
- overload is highly toxic
- bag of blood=bag of iron
IDA treated with dietary iron supplementation
ferrous sulfate, ferrous gluconate, ferrous fumarate
Special cases of IDA tx
Parenteral iron
iron dextran, sodium ferric gluconate, and iron sucrose
*colloid conatining a core of iron oxyhydroxide surrounded by core of carbohydrate
Iron intoxication
occurs most commonly via accidental ingestion of iron supplements by children
Describe the coure of iron inxication
necrotizing gastritis, shock, metabolic acidosis, and death
tx of acute iron intoxication
deferoxamine–> parenteral chelates circulating iron
*also remove undigested tabs and correct electrolyte abnormalities
iron overload occurs in
2 types
hemochromatosis
primary-> genetic defect in HFE gene–> cant turn off hepcidin
secondary–> chronically transfused as in beta thalassemia
symptoms of Hemochromatosis
free iron deposits in Heart, Liver and pancreas and other adrenal glands
gives you *cirrhosis and diabetes
tx of chronic iron overload
usually phlebotomy except if anemia
*deferasirox–> chelates free iron–> oral
With phlebotomy for Iron overload–> iron is first depleted from
ferritin stores first
then plasma iron
B12 defiency causes build up of
homocystein and methylmalonic acid
folate deficiency seen in
pregnancy
*lack of it causes NTD
causes CNS problems
b12–> methylmanolic acid build up
b12 required to conver methylmanolic acid into succinyl coa
Tx of megaloblastic anemia with folate only leaves the risk of
not getting rid of CNS defects–> you will correct the anemia and think the pt is doing better–> but not
–> must make sure it is a pure folate deficicneyc before you just administer folate
describe B12 absorption
first bound to haptocorin (r binder) present in salive which travels to the jejunum where B12 is released from haptocorin by degrdation of pancreatic proteases–> then it is bound to IF in the jejunum (but IF is produced by the pareital cells in the stomach–> them Cobalamin + IF travel to the distal illeum where they are taken up by transcobalamin II
tx of B12 deficiency
cyanocobalamin and hydroxocobalamin
which b12 tx has longer half life
hydroxocobalamin
B12 is stored in the
liver–> large reserve–> enough to last a vegan 5 years
b12 defiiency causes folate to accumulate as
N methyl THF
- folate is depleted over time
- production of RBC’s slows
B12 replacement therapy should always be
parenteral–> bc lack of it is usally due to malabsorption such as in pernitious anemia
why is folate important–>
DNA SYNTHESIS–> converted to dTMP–> THYMINE eventually–> without it DNA synthesis stops and cell become megaloblastic
Folate is stored
modest amounts in the body–> run out in a few months
DHFR
converts folate to DHF–>THF
folic acid is different than dietary folate how?
dietary folate must be demethylated
toxicity associated with folic acid/ b12
none
ESA’s used for anemias associated with
renal failure primary bone marrow failure anemia of cancer or chemo HIV/AIDS BMT
EPO is produced by the
kidney
*renal failure= anemia
list ESA’s
Epoietin alfa (recombinant human EPO)
darbepoietin alfa
Methoxy polyethylene glycol-epoitein beta
–>long-lasting EPO adminstered 2 x monthly
ESA with longest half life
darbepoitein alfa
*glycosylated form of EPO
most common ADE’s of ESA are
hypertension and thrombosis
HGB concentration of ppl undergoing ESA tx should not exceed
12–> any higher and you get adevrse CV events
Used to accelerate recovery of neutrophils after chemo
Gcsf- neutrophils specifically and majorly HSC’s
GMCSF–> all granulocytes and minimally Hematopoietic Stem Cells
What should you give a pt who has just gotten autologous stem cell transplant
Gcsf–. reduces tim to engraftment and increases neutrophils
Hematopoietic stem cell mobilozer
plerixafor–> inhibitor of CXCR4
May be combined with GCSF in myeloma pt.s who do not respond well to just GCSF
used to mobilize HSC’s prior to allogenic or autologous HSCT
GCSF
side effects of GSCF
minimal bone pain
side effects of GMCSF
fever, arthralgias, capillary damage
GCSF formulation with with longer
pegfilgrastim
Stimulates growth of megakryocytes
Oprevelkin IL-11
indications for Oprevelkin
pt.s with thrombocytopenia following chemo–> reduces need for platelet transfusions
TPO receptor agonist
romiplastin
eltrompobag
TPO receptor
c-MPL
ROute and indication for Romiplastin
Sub-Q
*pt’s with ITP who have responded poorly to conventional tx
Route and indication for eltropobag
oral
*ITP with poor response to conv. tx
major toxicity of eltropbag
hepatotoxicity
TPO is made in the
liver and kidney
EPO WORKS THROUGH
jak2 signaling cascade
ESAs should be used only in patients with cancer
–>treating anemia specifically caused by chemotherapy, and not for other causes of anemia. Further, it states that ESAs should be discontinued once the patient’s chemotherapy course has been completed.
ESA’S SHOULD NOT BE USED
for anemia that exists outside of the chemotherapy given to the pt.
darbepoietin contraindicated in
pt.’s with preexisting HTN
