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Heme & Lymph > Pharm of Anemia; Hematopoietic GFs > Flashcards

Pharm of Anemia; Hematopoietic GFs Flashcards

1
Q

Vitamin B12 deficiency

A

can lead to megaloblastic anemia, GI sxs, neuro abnorms

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2
Q

chief dietary source of VitB12

A

meat, eggs, dairy

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3
Q

Common signs of anemia

A

Pallor, fatigue, dizziness, extertional dyspnea, other generalized sx of tissue hypoxia, & CV adaptations such as tachycardia, increased CO and vasodilation

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4
Q

Absence of adequate iron leads to what type of anemia?

A

Microcytic hypochromic anemia - small erythrocytes with insufficient hemoglobin are formed

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5
Q

Iron absorption

A

Duodenum & prox jejuni my

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6
Q

When iron stores are high/iron requirements are low

A

Absorbed iron is diverted into ferritin in the intestinal epithelial mucosal cells for storage

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7
Q

Increased concentration of serum transferrin is associated with

A

Iron store depletion and iron deficiency anemia

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8
Q

Iron storage

A

As ferritin (complex of iron and apo-ferritin)

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9
Q

High levels of free iron stimulate production of apoferritin to reduce

A

Iron toxicity

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10
Q

Oral iron therapy

A

Only ferrous salts should be used bc ferrous iron is most efficiently absorbed
-ferrous sulfate, ferrous gluconate, ferrous karate

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11
Q

Ferrous salts adverse effects

A

Nausea, epigastric discomfort, abd cramps, constipation, black stools and diarrhea

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12
Q

Iron dextran

A

Par enteral iron therapy
-IV infusion -> can admin at higher dose
Adverse effects include: HA, light-headed mess, fever, athralgias, N/V, back pain, flushing, urticaria, bronchospasm, anaphylaxis and death

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13
Q

Sodium ferry gluconate complex and iron-sucrose complex

A

Parenteral iron therapy
Only IV
Less likely to cause hypersensitivity rxns

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14
Q

Acute iron toxicity

A

Young children who accidentally ingest iron tablets
-sx: necrotizing gastroenteritis, accompained by vomiting and abd pain and bloody diarrhea followed by shock, lethargy, dyspnea
-followed by severe metabolic acidosis, coma, death
Tx= parenteral deferoxamine

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15
Q

Chronic iron toxicity

A

Excess iron deposits in heart, liver, pancreas, & other organs
-most common in pts with inherited hemochromatosis & pts who receive many red cell transfusions over a long period of time

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16
Q

Chronic iron toxicity tx

A

Intermittent phlebotomy

-oral iron chelator deferasirox reduces liver iron concentrations

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17
Q

Vitamin B12 (Cobalamin) deficiency

A

Leads to Megaloblastic anemia (take 5 yrs to develop if absorption stopped completely), GI sx and neuro abnorms
-stored primarily in the liver

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18
Q

B12 absorption

A

Absorbed after complexing with intrinsic factor (secreted by parietal cells); absorbed in distal ileum
-after absorption, B12 transported by transcobalamin I,II, III

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19
Q

2 enzymatic rxns require B12

A

Synthesis of AA methionine & synthesis of succinyl-CoA

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20
Q

B12 deficiency causes

A
  • Accumulation of N5-methylTHF and depletion of THF
  • accumulation of homocysteine -> incr serum levels
  • methylmalonic acid and methylmalonyl-CoA accumulate
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21
Q

Clinical manifestations of B12 deficiency

A

Megaloblastic, macrocytic anemia often with associated mild or mod leukopenia or thrombocytopenia and a characteristic hypercellular BM with an accumulation of Megaloblastic erythroid and other precursor cells
-neurologic syndrome associated with B12 def begins with paresthesias and peripheral nerves and weakness and progresses to spasticity, ataxia, & other CNS dysfxns

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22
Q

Folic acid

A

Required for synthesis of AAs, purines and DNA

23
Q

Major consequence of folic acid deficiency

A

Anemia

-cause of congenital malformations in newborns and may play a role in vascular dz

24
Q

Richest sources of folic acid

A

Yeast, liver, kidney, green veggies

25
Q

Unaltered Folic acid is absorbed

A

In the prox jejunum

26
Q

Once inside cells, N5-methylTHF is converted to THF by the demethylation rxn that requires

A

VitB12

27
Q

Folic acid deficiency results in

A

Megaloblastic anemia

-does not cause neurologic syndrome seen with B12 def

28
Q

Drugs that cause folic acid deficiency

A

Methotrexate, trimethoprim, and pyrimethamine (all inhib DHFR)

29
Q

Erythropoietin

A

Peritubular interstitial cells of the kidney

-binds to receptor on the surface of committed erythroid progenitors in the marrow after secretion

30
Q

Inflammatory CKs suppresses

A

Erythropoietin secretion, iron delivery, and progenitor proliferation

31
Q

RHuEPO, Epoetin alpha

A

IV admin

T 1/2 4-8 hrs but effects on marrow progenitors lasts much longer

32
Q

Darbepoetin alpha

A

Modified form of erythropoietin that is more glycosylated and has a half life of 24-26 hrs

33
Q

Erythropoietin pharmacodynamics

A

Induces erythropoiesis, induces release of reticulocytes from the BM into the bloodstream where they mature into erythrocytes
-result in incr in reticulocytes counts (10 days) followed by a rise in hematocrit and Hb levels (2-6 wks)

34
Q

Erythropoiesis-stimulating agents (ESAs)

A

Used in pts with anemia secondary to chronic kidney dz

  • always coupled with oral or parenteral iron supplementation (& sometimes folate) in pts with chronic kidney dz
  • may also be used for tx of anemia due to primary bone marrow disorders and secondary anemia so
35
Q

Adverse effects of erythropoietin

A

HTN and thrombolytic complications

36
Q

Myeloid GFs

A

Stimulate the proliferation and differentiation of one or more myeloid cells lines
-enhance the fxn of mature granulocytes and monocytes

37
Q

Filgrastim

A

Recombinant human G-CSF

  • nonglycosylated peptide
  • IV -> serum half life 2-3.5 hrs
38
Q

Pegfilgrastim

A

Covalent conjugation product of Filgrastim and polyethylene glycol (PEG)
Longer serum half life than Filgrastim

39
Q

Sargramostim

A

Recombinant human GM-CSF

40
Q

Plerixafor

A

Reversible inhibits binding of stromal cell-derived factor-1-alpha (SDF-1a) which is expressed on BM stromal cells, to the CXC chemokine receptor 4 (CXCR4)

  • results in mobilization of hematopoietic stem and progenitor cells from BM into PB
  • used in combo with Filgrastim results in synergistic incr in CD34+ cell mobilization prior to autologous transplantation
  • used in pts who respond sub optimally to G-CSF alone
41
Q

G-CSF

A

Stimulates prolif and diff of progenitors already committed to the neutrophil lineage

  • activates the phagocytic activity of mature NTs and prolongs survival
  • Increases conc of HSCs in the PB
42
Q

GM-CSF

A

Stimulate myelopoiesis -> prolif and diff of early and late granulocytic progenitor cells as well as erythroid and megakaryocytes progenitors

  • stimulates the fxn of mature NTs
  • stimulates T-cell proliferation together with IL-2
43
Q

Cancer chemotherapy-induced neutropenia

A

G-CSF accelerates the rate of NT recovery after myelosuppressive chemo & reduce duration of neutropenia
G-CSF reduces episodes of febrile neutropenia, Reqs for broad-spectrum antibiotics, infxs, & days of hospitalization

44
Q

Pegfilgrastim vs Filgrastim

A

Pegfilgrastim may be admin less frequent and may shorten period of severe neutropenia

45
Q

Filgrastim & Pegfilgrastim

A

Used more freq than GM-CSF -> better tolerated

Can cause bone pain

46
Q

GM-CSF toxicity

A

Fever, malaise, athralgias, and a capillary leak syndrome characterized by peripheral edema and pleural or pericardial effusions

47
Q

Megakaryocytes GFs

A

Pts with thrombocytopenia have a high risk of hemorrhage

Thrombopoietin and IL-11 are endogenous regulators of platelet production

48
Q

IL-11: Oprelvekin

A

Recombinant form
Activates specific cell surface CK receptors to stimulate the growth of multiple lymphoid and myeloid cells, stimulate the growth of primitive megakaryocytic progenitors; increases # of peripheral platelets and NTs

49
Q

Romiplostim (recombinant thrombopoietin)

A

Activates Mpl thrombopoietin receptor to cause a dose-dependent increase in platelet count
Increase in platelets begins 5 days after subQ injection, peaks 12-15 days

50
Q

IL-11 is approved for

A

Secondary prevention of thrombocytopenia in pts receiving cytotoxic chemotherapy for no myeloid cancers

51
Q

Romiplostim is approved for

A

Treatment of thrombocytopenia in pts with chronic immune (idiopathic) thrombocytopenia purpura (ITP)

52
Q

IL-11 toxicity

A

Fatigue, headache, dizziness, CV effects (anemia, dyspnea, transient atrial arrhythmias

  • hypokalemia
  • all are reversible
53
Q

Romiplostim toxicity

A

Well tolerated except for a mild HA on day of admin

Heme & Lymph (8 decks)

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