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LHT1 > Pharmacology of Anemia > Flashcards

Pharmacology of Anemia Flashcards

1
Q

iron- oral preparations- drugs

A
  • ferrous sulfate
  • ferrous gluconate
  • ferrous fumarate
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2
Q

iron- parenteral preparations- drugs

A
  • iron dextran
  • iron-sucrose complex
  • sodium ferric gluconate complex
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3
Q

iron chelators- drugs

A
  • deferoxamine

- deferasirox

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4
Q

vit B12 preparations- drugs

A
  • Cyanocobalamin

- Hydroxocobalamin

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5
Q

Erythrocyte-stimulating agents- drugs

A
  • Epoetin alpha

- Darbepoetin alpha

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6
Q

Myeloid GFs- drugs

A
  • G-CSF (granulocyte colony-stimulating factor)- Filgrastim, pegfilgrastim
  • GM-CSF- Sargramostim
  • Plerixafor
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7
Q

Megakaryocyte GFs- drugs

A
  • Oprelvekin, IL-11

- Romiplostim

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8
Q

iron def- causes what?

A

-microcytic hypochromic anemia

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9
Q

iron absorption- where?

A

-duodenum and jejunum

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10
Q

iron absorption- when iron stores are low- what happens?

A
  • abs iron is transported from mucosal cells to bone marrow to support hemoglobin production
  • transported by transferrin
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11
Q

clinical scenarios and iron transport

A
  • increased erythropoiesis- inc in transferrin Rs on developing erythroid cells
  • iron store depletion- inc conc of serum transferrin
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12
Q

iron storage

A
  • stored as ferritin

- stored in intestinal mucosal cells, macrophages in liver, spleen, bone and in parenchymal liver cells

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13
Q

iron treatment- used for?

A

tx or prevention of iron def anemia

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14
Q

oral iron therapy- what is used?

A
  • ferrous salts- b/c ferrous iron is most efficiently absorbed
  • 25% or oral iron given as ferrous salts can be absorved
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15
Q

oral iron therapy- adverse effects

A

-nausea, epigastric discomfort, abd cramps, constipation, black stools, diarrhea
(reduced if taken with/after meals)

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16
Q

parenteral iron therapy- used for?

A
  • pts with iron deficiency who cant tolerate or absorb oral iron
  • pts with extensive chronic anemia who cant be maintained with oral iron alone
  • can deliver more iron than can be safely be stored- bypasses iron storage regulatory mechanisms of the intestine
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17
Q

iron dextran- route, adverse effects

A
  • IM injection or IV infusion (most common)
  • HA, light-headedness, fever, arthralgias, N/V, back pain, flushing, urticaria, bronchospasm
  • small test dose- check for hypersensitivity rxns!
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18
Q

Sodium ferric gluconate complex and iron-sucrose complex- route

A
  • IV

- less likely to cause hypersensitivity rxns

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19
Q

Acute iron toxicity- in who? sx? tx?

A
  • in young children who accidentally ingest iron tablets
  • necrotizing gastroenteritis, vomiting, abd pain, bloody diarrhea- followed by shock, lethargy, dyspnea
  • improvement may be noted followed by severe metabolic acidosis, coma, death!
  • tx- whole bowel irrigation, parenteral deferoxamine (iron-chelating compound)
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20
Q

chronic iron toxicity (hemochromatosis)- causes what? in who? tx?

A
  • iron deposits in heart, liver, pancreas, other organs- organ failure and death
  • in pts with inherited hemochromatosis- disorder of excessive iron abs
  • also in pts who have received many red cell transfusions over a long time
  • tx- phlebotomy
  • deferasirox- reduces liver iron conc
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21
Q

vit B12 def- causes what?

A

megaloblastic anemia, GI sx, neuro abnormalities

-B12 stored in liver; low daily requirement- if B12 abs stopped completely, it would take 5 yrs to develop anemia!!!

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22
Q

Vit B12- source from?

A

microbial synthesis

23
Q

B12 absorption- occurs how? where? def due to?

A
  • absorbed after complexing with intrinsic factor (secreted by parietal cells of gastric mucosa)
  • absorption in ileum
  • def due to lack of IF or loss/malfxn of absorption in the ileum
24
Q

2 essential enzymatic rxns in humans require B12

A
  • synthesis of methionine (aa)

- synthesis of succinyl-CoA

25
Q

synthesis of methionine

A
  • Homocysteine –> methionine
  • requires cobalamin: N5-methyltetrahydrofolate–> tetrahydrofolate –> methylcobalamin: homocysteine–> methionine
  • B12 def- causes accum of N5-methyltetrahydrofolate and depletion of tetrahydrofolate; accum of homocysteine
  • inc serum levels of homocysteine- diagnostic of B12 def!!!
26
Q

synthesis of succinyl-CoA- B12 def

A
  • methylmalonic acid and methylmalonyl CoA accum

- diagnostic- serum and urine levels of methylmalonic acid!!

27
Q

causes of B12 def?

A
  • pernicious anemia
  • partial or total gastrectomy
  • conditions that affect distal ileum
  • almost all due to malabsorption- need parenteral injections for tx!
28
Q

B12 def- clinical manifestations

A
  • megaloblastic, macrocytic anemia
  • mild/moderate leukopenia or thrombocytopenia
  • hypercellular bone marrow with accum of megaloblastic erythroid cells
  • paresthesias in peripheral n’s and weakness
29
Q

B12 def- tx?

A

(almost all due to malabsorption- need parenteral injections for tx!)
-cyanocobalamin and hydroxocobalamin

30
Q

folic acid def- causes what?

A
  • megaloblastic anemia! (same as B12)
  • also congenital malformations in newborns
  • doesnt cause the neuro syndrome seen in B12
31
Q

folic acid- sources? def caused by?

A

diet- yeast, liver, kidney, green vegetables

-def caused by inadequate intake of folates (alcoholics, pregnant women

32
Q

folic acid def- tx?

A

-PO folic acid

33
Q

Erythropoietin- physiology

A
  • in peritubular interstitial cells of kidney
  • binds to a R on the surface of committed erythroid progenitors in the marrow after secretion- initiates JAK/STAT signal pathway
  • anemia/hypoxia- synthesis inc by 100-fold or more- marrow progenitor cell survival, prolif, maturation stimulated!
  • infl cytokines suppress erythropoietin secretion
34
Q

Erythropoietin- moa

A
  • induces erythropoiesis by stim the division and diff of committed erythroid progenitor cells
  • induces the release of reticulocytes from bone marrow into bloodstream, where they mature to erythrocytes
  • results in inc in reticulocyte counts (10 days), and a rise in hematocrit and hemoglobin levels (2-6 wks)
35
Q

ESAs (erythropoiesis-stimulating agents)- used in who?

A

pts w/ anemia secondary to chronic kidney dz

  • coupled with oral or parenteral iron supplementation in pts with chronic kidney dz
  • also used to treat anemia due to primary bone marrow disorders and secondary anemias
36
Q

ESAs- toxicity

A
  • iron def- can be overcome with supplementation

- hypertension, thrombotic complications

37
Q

Myeloid GFs- fxn?

A
  • stim the prolif and diff of 1 or more myeloid cell lines
  • enhance the fxn of mature granulocytes and monocytes
  • bind to and activate members of the cytokine R superfamily
38
Q

Myeloid GFs- available for clinical use

A
  • G-CSF

- GM-CSF

39
Q

Filgastrim

A
  • recombinant human G-CSF

- half-life 2-3.5 hrs (IV)

40
Q

Pegfilgrastim

A
  • conjugation of filgrastim and polyethylene glycol

- longer half-life (15-80 hrs)

41
Q

Sargramostim

A
  • recombinant human GM-CSF

- half-life 1 hr (IV)

42
Q

Plerixafor- moa

A
  • reversibly inhibits binding of stromal cell-derived factor-1-alpha (SDF-1alpha), which is expressed on bone marrow stromal cells, to the CXCR4
  • results in mobilization of hematopoietic stem and progenitor cells from bone marrow into peripheral blood
  • used in combo with filgrastim- synergistic inc in CD34+ cell mobilization
  • used in pts who respond suboptimally to G-CSF alone
43
Q

G-CSF- moa

A
  • stim the prolif and diff or progenitors already committed to the neutrophil lineage
  • act the phagocytic activity of mature neutrophils and prolongs survival
  • inc conc of hematopoietic stem cells in peripheral blood
44
Q

GM-CSF- moa

A

broader biologic actions than G-CSF

  • stimulates myelopoiesis
  • stim prolif and diff of eraly and late granulocytic progenitor cells, as well as erythroid and megakaryocyte progenitors
  • stim fxn of mature neutrophils
  • stim T-cell prolif with IL-2
45
Q

myeloid GFs- used for?

A

cancer chemotherapy-induced neutropenia

-G-CSF accelerates the rate of neutrophil recovery, reduces the duration of neutropenia

46
Q

myeloid GFs- toxicity

A
  • filgrastim and pegfilgrastim- used more than GM-CSF- better tolerated; both cause bone pain
  • GM-CSF- fever, malaise, myalgias, capillary leak syndrome (peripheral edema, pleural or pericardial effusions)
47
Q

megakaryocyte GFs- pts with thrombocytopenia have high risk of

A

hemorrhage

-thrombopoietin and IL-11- endogenous regulators of platelet production

48
Q

IL-11- drug, moa

A

Oprelvekin
-act specific cell surface cytokine Rs to stim the growth of mult lymphoid and myeloid cells; inc the number of platelets and neutrophils

49
Q

Romiplostim- moa

A

(recombinant thrombopoietin)

-act Mpl thrombopoietin R to cause a dose-dep inc in platelet count

50
Q

IL-11- used for?

A

-secondary prevention of thrombocytopenia in pts receiving cytotoxic chemotherapy for nonmyeloid cancers

51
Q

Romiplostim- used for?

A

-tx of thrombocytopenia in pts with chronic immune thrombocytopenia purpura

52
Q

IL-11- toxicity

A
  • fatigue, HA, dizziness, CV effects

- hypokalemia

53
Q

Romiplostim- toxicity

A

mild headache on day of administration

LHT1 (6 decks)

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