Pharmacological Treatment of Anemia - KMS Flashcards
(126 cards)
1
Q
How much elemental Fe is absorbed each day from diet?
A
0.5-1 mg absorbed/day from 10-15 mg elemental iron in the average diet
2
Q
Where is Fe absorbed in the GI tract?
A
primarily in the duodenum and proximal jejunum
3
Q
How can Fe absorption in the GI tract increase?
A
Increases in response to low iron stores or increased iron requirements
4
Q
What form of Fe can be absorbed completely and without change to it?
A
Heme iron in hemoglobin and myoglobin
can be absorbed intact without first having to be dissociated into elemental iron (e.g., iron in meat protein)
5
Q
Heme Fe can be absorbed intact, but how is nonheme Fe absorbed?
A
Nonheme iron must be reduced by ferroreductase to ferrous iron (Fe2+) before absorption can occur
6
Q
What happens to absorbed Fe when Fe stores are high, or requirements are low?
A
When iron stores are high and/or iron requirements are low,
absorbed iron is diverted into ferritin in the intestinal epithelial mucosal cells for storage
7
Q
What happens to absorbed Fe when stores are low or requirements are high?
A
When iron stores are low and/or iron requirements are high,
absorbed iron is immediately transported from the mucosal cells to the bone marrow to support hemoglobin production
8
Q
What transports Fe in plasma?
A
Transferrin
– a β-globulin that binds two molecules of ferric iron (Fe3+) and transports iron in the plasma
9
Q
Fe is shuttled around by transferrin, but how does it get into RBCs?
A
The transferrin-iron complex enters maturing erythroid cells by binding to integral membrane glycoprotein receptors (transferrin receptors) and undergoing receptor-mediated endocytosis
The ferric iron is released in endosomes, reduced to ferrous iron, transported by the divalent metal transporter (DMT1) into the cell, and enters the hemoglobin synthesis pathway or is stored as ferritin
10
Q
What can increase the number of transferrin receptors on developing erythroid cells?
A
Increased erythropoiesis
11
Q
What is associated with an increased conc. of serum transferrin?
A
Iron store depletion and iron deficiency anemia are associated with an increased concentration of serum transferrin
12
Q
What form is iron stored as? Where?
A
almost always stored as ferritin (ferritin is the complex of iron and apo-ferritin, a transferrin-like protein that binds ferrous iron for storage)
stored in intestinal mucosal cells, in macrophages in the liver, spleen, and bone, and in parenchymal liver cells
13
Q
How do levels of free Fe change Fe storage?
A
Low levels of free iron inhibit apoferritin synthesis and shifts the balance of iron binding toward transferrin
High levels of free iron stimulate production of apoferritin to reduce iron toxicity
14
Q
How is Fe eliminated?
A
There is no specific mechanism for iron excretion
Iron balance is achieved by changing intestinal absorption and storage of iron in response to the body’s needs
15
Q
What is the clinical indication for Fe preparations?
A
The only clinical indication for the use of iron preparations is the treatment or prevention of iron deficiency anemia
16
Q
What type of Fe salts should be used for oral Fe therapy?
A
Only ferrous salts should be used because ferrous iron is most efficiently absorbed
(e.g., ferrous sulfate, ferrous gluconate, ferrous fumarate)
17
Q
How much oral Fe is absorbed?
A
Roughly 25% of oral iron given as ferrous salt can be absorbed
18
Q
How does oral absorption of oral Fe therapy affect dosing? What is the typical dose?
A
50-100 mg of iron can be incorporated into hemoglobin daily in an iron-deficient individual; 200-400 mg iron/day is a typical dose
19
Q
How should oral iron therapy be taken?
A
Should be taken with water or juice on an empty stomach; may be administered with food to prevent irritation
20
Q
What are some ADRs with PO Fe therapy?
A
Adverse effects include
nausea,
epigastric discomfort,
abdominal cramps,
constipation,
black stools, and
diarrhea (dose related; reduced if taken with or immediately after meals)
21
Q
How can GI discomfort be reduced with PO Fe therapy?
A
Switching to a different ferrous salt preparation may reduce GI discomfort
22
Q
Who is a candidate for parenteral Fe therapy?
A
Reserved for patients with documented iron deficiency who are unable to tolerate or absorb oral iron
and for patients with extensive chronic anemia who cannot be maintained with oral iron alone
(e.g., patients with advanced chronic renal disease requiring hemodialysis and treatment with erythropoietin, small bowel resection, inflammatory bowel disease involving the proximal small bowel, or malabsorption syndromes)
23
Q
How are parenteral forms of Fe formulated?
A
All parenteral forms of iron are formulated as colloid containing particles with a core of iron oxyhydroxide surrounded by a core of carbohydrate
so that iron is released slowly from the stable colloid particle after infusion
(avoids the severe toxicity of free ferric iron upon administration)
24
Q
Why is parenteral administration of Fe favored sometimes?
A
bypasses iron storage regulatory mechanisms of the intestine and can deliver more iron than can safely be stored;
monitoring iron storage levels helps to avoid serious toxicity of iron overload
25
What are the 3 forms of parenteral Fe available in the US?
Iron dextran
Sodium ferric gluconate complex
Iron sucrose complex
26
How is Fe dextran administered? Which way is most common?
May be administered by deep IM injection or by IV infusion (most common because it eliminates local pain and tissue staining that occurs with IM injections and can administer a higher dose in comparison to IM)
27
What are the ADRs associated with Fe dextran? What should you try before administering it?
Adverse effects include headache, light-headedness, fever, arthralgias, nausea, vomiting, back pain, flushing, urticaria, bronchospasm, and anaphylaxis and death (rare)
A small test dose should always be given due to hypersensitivity reactions
28
How is Na Fe+++ gluconate complex administered?
Only administered IV
Less likely to cause hypersensitivity reactions
29
How is Fe sucrose complex administered?
IV only
30
Which 2 parenteral Fe therapies are less likely to cause hypersensitivity reactions?
Sodium ferric gluconate complex
Iron sucrose complex
31
What population is acute Fe toxicity seen in?
almost exclusively in young children who accidentally ingest iron tablets
(as few as 10 tablets of common iron preparations can be lethal)
32
What are the symptoms of acute Fe toxicity?
necrotizing gastroenteritis,
accompanied by vomiting and abdominal pain,
and bloody diarrhea
followed by shock, lethargy, and dyspnea
33
What can acute Fe toxicity ultimately result in?
Improvement may be noted and followed by:
severe metabolic acidosis, coma, and death
34
How can acute Fe toxicity be treated? What common poisoning treatment is ineffective?
Urgent treatment includes whole bowel irrigation and parenteral **deferoxamine** (potent iron-chelating compound that promotes excretion in feces and urine)
Activated charcoal does not bind iron and is ineffective
35
What is another name for chronic Fe toxicity?
hemochromatosis
36
Where can excess Fe deposits cause major damage? What can this lead to?
Excess iron deposits in the heart, liver, pancreas, and other organs can lead to organ failure and death
37
In what population of patients is hemochromatosis most common?
Toxicity is most common in patients with:
inherited hemochromatosis, (a disorder characterized by excessive iron absorption)
and in patients who receive many red cell transfusions over a long period of time
38
How is chronic Fe toxicity treated?
Efficiently treated with intermittent phlebotomy
(deferoxamine is less efficient and potentially hazardous but may be only option for iron overload unsuccessfully managed by phlebotomy)
39
What can reduce liver Fe concentrations?
Oral iron chelator **deferasirox** reduces liver iron concentrations
but data in removing iron from heart is lacking
40
What can cobalamin deficiency lead to?
1. **VITAMIN B12 (COBALAMIN)**
Essential cofactor in humans; deficiency can lead to megaloblastic anemia, gastrointestinal symptoms, and neurologic abnormalities
41
What are the sources of B12?
common dietary sources are meat, eggs, and dairy products
Vitamin B12 is naturally synthesized by microorganisms, but humans are incapable of doing so and must obtain vitamin B12 in their diet
Porphyrin-like ring with a central cobalt atom attached to a nucleotide
42
What are the active forms of cobalamin in humans?
Cyanocobalamin (synthetic), hydroxocobalamin, and other cobalamins found in food sources are converted to
deoxyadenosylcobalamin and methylcobalamin, the active forms in humans
43
What forms of cobalamin are available for clinical use?
Both cyanocobalamin and hydroxocobalamin are available for clinical use
44
How much cobalamin is absorbed daily, and where is it stored?
Average diet in the USA contains 5-30 mcg/day; 1-5 mcg vitamin B12 is typically absorbed; daily requirement is approximately 2 mcg
Stored primarily in the liver (3000-5000 mcg total); only trace amounts are lost in the urine and stool
45
If someone were to take in no more vitamin B12, what ill effects would they see and when?
Due to the amount of B12 stored and low daily requirement, if B12 absorption stopped completely it would take about 5 years to develop megaloblastic anemia
46
What is essential to the absorption of vitamin B12?
B12 is only absorbed after complexing with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa (absorption occurs in the distal ileum by a highly selective receptor-mediated transport system)
47
What is a B12 deficiency often a result of?
B12 deficiency most often results from malabsorption due to lack of intrinsic factor or to loss or malfunction of the absorptive mechanism in the distal ileum; nutritional deficiency is rare but may be seen in strict vegetarians after many years
48
How is B12 transported after absorption?
B12 is transported by the glycoproteins transcobalamin I, II, and III
(excess is transported to the liver for storage)
49
What 2 essential enzymatic rxns in humans require B12?
synthesis of the amino acid methionine and the synthesis of succinyl-CoA
50
The synthesis of methionine requires vitamin B12. What is another product that gets made during this reaction?
tetrahydrofolate
51
How are B12 and folate deficiency linked?
B12 deficiency causes the accumulation of N5-methyltetrahydrofolate (Tetrahydrofolate precursor) and depletion of tetrahydrofolate
(link between B12 and folic acid metabolism; B12 deficiency can be partially corrected by ingestion of large amounts of folic acid, which largely corrects the anemia caused by B12 deficiency; folic acid does not prevent neurologic manifestations of B12 deficiency, which are thought to be caused by loss of methionine synthesis
52
In addition to tetrahydrofolate deficiency, what else can B12 deficiency cause?
B12 deficiency causes the accumulation of homocysteine due to the reduced formation of methylcobalamin
53
How can B12 deficiency be measured?
In patients deficient in B12, methylmalonic acid and methylmalonyl-CoA accumulate (serum and urine levels of methylmalonic acid are diagnostic for B12 deficiency)
B12 deficiency causes the accumulation of homocysteine due to the reduced formation of methylcobalamin; increased serum levels are diagnostic of B12 deficiency
54
What are some common causes of B12 deficiency?
pernicious anemia,
partial or total gastrectomy,
and conditions that affect the distal ileum (e.g., malabsorption syndromes, inflammatory bowel disease, small bowel resection)
55
What are the most common characteristic clinical manifestations of B12 deficiency?
megaloblastic, macrocytic anemia, often with associated mild or moderate leukopenia or thrombocytopenia (or both),
and a characteristic hypercellular bone marrow with an accumulation of megaloblastic erythroid and other precursor cells
56
What is the neurologic syndrome associated with vitamin B12 deficiency?
deficiency usually begins with paresthesias in peripheral nerves and weakness; it progresses to spasticity, ataxia, and other CNS dysfunctions (B12 treatment stops the progression of neurologic disease but may not fully reverse neurologic symptoms)
57
What are almost all cases of B12 deficiency caused by? How does this affect therapy/treatment?
Almost all cases of B12 deficiency are due to malabsorption; therefore, parenteral injections are required for therapy (often lifelong if syndrome causing deficiency is incurable)
58
What forms of B12 are available for parenteral injections?
cyanocobalamin and hydroxocobalamin forms of B12
59
What is the dosing for B12 therapy?
Initial therapy: 100-1000 mcg B12 IM daily or every other day for 1-2 weeks to replenish body stores
Maintenance therapy: 100-1000 mcg B12 IM once a month for life
60
What is the dosing for B12 deficiency if neurological symptoms are present?
If neurologic abnormalities are present, maintenance therapy should be given every 1-2 weeks for 6 months before switching to monthly injections
Maintenance therapy: 100-1000 mcg B12 IM once a month for life
61
What administration of B12 is an acceptable alternative to injections?
Oral and intranasal administration of B12 are usually sufficient to treat patients with pernicious anemia who refuse or cannot tolerate injections
62
What is folic acid required for?
Required for synthesis of amino acids, purines, and DNA
63
What is the major consequence of folic acid deficiency? What else does it play a role in?
Major consequence of deficiency is anemia;
folic acid deficiency is implicated as a cause of congenital malformations in newborns and
may play a role in vascular disease
64
How much folic acid is absorbed daily? How much is stored?
Average US diet contains 500-700 mcg of folates daily;
50-200 mcg are absorbed in the typical individual (300-400 mcg absorbed daily in pregnant women);
5-20 mg folates are stored in the liver and other tissues
65
What are the richest dietary sources of folic acid?
yeast, liver, kidney, and green vegetables
66
How are folates excreted? How quickly can serum levels fall?
Folates are excreted in the urine and stool and destroyed by catabolism; serum levels fall within a few days when intake is diminished
67
What can develop after intake of folic acid stops?
Due to relatively low body stores and high daily requirements, folic acid deficiency and megaloblastic anemia may develop within 1-6 months after the intake of folic acid stops
68
Where is folic acid absorbed?
Unaltered folic acid is absorbed in the proximal jejunum
69
What form does dietary folates consist of? What must happen to it before it is changed to tetrahydrofolate?
Dietary folates consist primarily of polyglutamate forms of *N*5-methyltetrahydrofolate; all but one glutamyl residue of the polyglutamates must be hydrolyzed by the enzyme α-1-glutamyl transferase within the brush border of the intestinal mucosa before absorption
Once inside cells, N5-methyltetrahydrofolate is converted to tetrahydrofolate by the demethylation reaction that requires vitamin B12
70
What pathways is tetrahydrofolate important in, and why?
Tetrahydrofolate cofactors participate in one-carbon transfer reactions, which are essential components of synthesis pathways of amino acids, purines, and DNA
71
Why is tetrahydrofolate important in antineoplastic agents?
Considerable amounts of tetrahydrofolate are consumed by rapidly proliferating tissues;
enzymes in the dTMP cycle are the targets of two antineoplastic agents (methotrexate inhibits dihydrofolate reductase and 5-fluorouracil inhibits thymidylate synthase)
72
What does folic acid deficiency result in?
Folic acid deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency
73
How is megaloblastic anemia as a result of folic acid defiency versus B12 deficiency differentiated?
Folate deficiency does not cause the neurologic syndrome seen in B12 deficiency (folic acid therapy in B12 deficiency has no effect on neurologic symptoms)
74
What often causes folic acid deficiency?
Deficiency is often caused by inadequate dietary intake of folates
(e.g., alcoholics with poor diet and diminished hepatic storage,
pregnant women and
patients with hemolytic anemia with increased folate requirements,
patients with malaborption syndromes,
patients undergoing renal dialysis have folates removed from plasma)
75
What are some drugs that can cause folic acid deficiency?
methotrexate, trimethoprim, and pyrimethamine (all inhibit dihydrofolate reductase) and long-term therapy with phenytoin
76
How much folic acid is sufficient to reverse megaloblastic anemia?
1 mg/day PO folic acid is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores in almost all patients (even in patients with malaborption issues)
77
What patients should receive folic acid supplementation?
high-risk patients
alcoholics with poor diet and diminished hepatic storage,
pregnant women and
patients with hemolytic anemia with increased folate requirements,
patients with malaborption syndromes,
patients undergoing renal dialysis have folates removed from plasma
78
What type of products are hematopoietic growth factors? What is their general purpose?
glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells in bone marrow
79
What do hematopoietic growth factors treat?
Hematopoietic agents and drugs that mimic their action are used to treat various conditions, such as anemia and cancer (patients may require treatment for neutropenia, thrombocytopenia, and stem cell transplantation)
80
Where is erythropoietin normally expressed?
peritubular interstitial cells of the kidney
81
What does EPO (erythropoietin) bind to cause an effect?
Binds to a receptor on the surface of committed erythroid progenitors in the marrow after secretion
(erythropoietin receptors are members of the cytokine receptor superfamily and initiate the JAK/STAT signal transduction pathway (kinase signaling cascade))
82
What can rapidly cause EPO levels to rise? What is the result?
With anemia or hypoxemia, synthesis rapidly increases by 100-fold or more, serum erythropoietin levels rise, and marrow progenitor cell survival, proliferation, and maturation are stimulated
(can be disrupted by kidney disease, marrow damage, or a deficiency in iron or an essential vitamin)
83
What can disrupt EPO secretion?
Inflammatory cytokines, released due to an infection or an inflammatory state, suppress erythropoietin secretion, iron delivery, and progenitor proliferation (inflammation also affects iron metabolism)
84
What are the names for recombinant human erythropoietin products?
**rHuEPO, epoetin alpha**
85
How is epoetin alpha made? ROA?
Produced in a mammalian cell expression system for IV administration
86
How is epotein alpha dosed?
Half-life 4-8 hours but effects on marrow progenitors lasts much longer, allowing for once-weekly dosing to produce an adequate response
Administered 3x/week in patients with chronic renal failure (not cleared by dialysis)
87
What is darbepoetin alpha? Methoxy polyethylene glycol-epoetin beta?
a type of recombinant human erythropoietin
modified form that is more glycosylated and has a half-life of 24-26 hours
Methoxy polyethylene glycol-epoetin beta: long-acting isoform administered 1-2x/month
88
What is the MOA of recombinant EPO?
**MOA**: induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells;
induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes (agonist at erythropoietin receptors on red cell progenitors)
89
What is the ultimate result of recombinant EPO therapy?
Results in an increase in reticulocyte counts (10 days) followed by a rise in hematocrit and hemoglobin levels (2-6 weeks)
90
How are recombinant EPO agents used clinically? In combination with what drugs?
Erythropoiesis-stimulating agents (ESAs) are used to decrease the need for RBC transfusions in patients with anemia secondary to chronic kidney disease (endogenous erythropoietin levels are low because the kidneys cannot produce the growth factor)
Nearly always coupled with oral or parenteral iron supplementation (and sometimes folate supplementation) in patients with chronic kidney disease
91
In addition to eryropoiesis in chronic kidney disease, what are 3 other indications for recombinant EPO?
Treatment of anemia due to concurrent myelosuppressive chemotherapy in patients with cancer (nonmyeloid malignancies) receiving chemotherapy (palliative intent) for a planned minimum of 2 additional months of chemotherapy
Treatment of anemia associated with HIV (zidovudine) therapy when endogenous erythropoietin levels ≤ 500 mUnits/mL
Reduction of allogenic RBC transfusion for elective, noncardiac, nonvascular surgery when perioperative Hgb is 10-13 g/dL and there is a high risk for blood loss
92
What conditions are erythropoiesis stimulating agents (ESAs) not indicated for?
(1) Cancer patients receiving hormonal therapy, therapeutic biologic products, or radiation therapy unless also receiving concurrent myelosuppressive chemotherapy
(2) Cancer patients receiving myelosuppressive chemotherapy when the expected outcome is curative
(3) Surgery patients who are willing to donate autologous blood
(4) Surgery patients undergoing cardiac or vascular surgery
(5) As a substitute for RBC transfusion in patients requiring immediate correction of anemia
93
What is an off-label use for ESAs?
treatment of symptomatic anemia in myelodysplastic syndrome (MDS)
94
Are ESAs considered a performance enhancing drug?
yes - Banned by the International Olympic Committee
95
What are the most common ADRs with ESAs?
Most common adverse effects are hypertension and thrombotic complications (may require increased anticoagulation);
aggressive use in patients with chronic renal failure or cancer has been linked to increased mortality and CV events, reduce risk by using lowest dose needed
Allergic reactions are uncommon
96
What patients are ESAs contraindicated?
Contraindicated in patients with uncontrolled hypertension
97
What are the 2 categories of myeloid growth factors?
Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are two myeloid growth factors currently available for clinical use
98
What are the 3 myeloid growth factors for right now?
Filgrastim (rHuG-CSF)
Pegfilgrastim
Sargramostim (rHuGM-CSF)
99
What is filgrastim? How is it made?
Recombinant human G-CSF produced in a bacterial expression system
Nonglycosylated peptide of 175 amino acids
100
What is the half life of filgrastim? ROA?
Serum half-life approximately 3.5 hours after IV or subcutaneous administration
101
What is pegfilgrastim?
Covalent conjugation product of filgrastim and polyethylene glycol (PEG)
102
What is the half life of pegfilgrastim? MOA?
1. Longer serum half-life than filgrastim (15-80 hours)
2. Can be injected once per myelosuppressive chemotherapy cycle instead of daily for several days
103
What is sargramostim?
Recombinant human GM-CSF produced in a yeast expression system
Glycosylated peptide of 127 amino acids
104
What is the half life of sargramostim? ROA?
IV half-life approximately 1 hour; SubQ half-life approximately 3 hours
105
What do myeloid growth factors do? What receptors do they work on?
Myeloid growth factors stimulate proliferation and differentiation of one or more myeloid cell lines and enhance the function of mature granulocytes and monocytes
Receptors for myeloid growth factors are members of the cytokine receptor superfamily and initiate the JAK/STAT signal transduction pathway
106
What are the 3 actions of G-CSF?
1. Stimulates proliferation and differentiation of progenitors already committed to the neutrophil lineage
2. Activates the phagocytic activity of mature neutrophils and prolongs survival
3. Increases concentration of hematopoietic stem cells in peripheral blood (major advance in transplantation because peripheral blood stem cells (PBSCs) may be used rather than bone marrow stem cells)
107
How does GM-CSF differ from G-CSF?
Broader biologic actions than G-CSF
Primary therapeutic effect is to stimulate myelopoiesis
108
What are the 4 actions of GM-CSF?
1. Stimulates the proliferation and differentiation of early and late granulocytic progenitor cells as well as erythroid and megakaryocyte progenitors
2. Stimulates the function of mature neutrophils
3. Stimulates T-cell proliferation together with interleukin-2
4. Increases concentration of peripheral blood stem cells to a lesser extent than G-CSF
109
How can G-CSF help cancer chemotherapy-induced neutropenia?
G-CSF has been shown to dramatically accelerate the rate of neutrophil recovery after dose-intensive myelosuppressive chemotherapy, reduce the duration of neutropenia, and raise the nadir count (low-point of neutrophil count) following a cycle of chemotherapy
Clinical trials have shown that G-CSF reduces episodes of febrile neutropenia, requirements for broad-spectrum antibiotics, infections, and days of hospitalization, but have not shown improved survival in cancer patients
110
How is administration of pegfilgrastim different from filgrastim in treatment for cancer chemotherapy-induced neutropenia?
Pegfilgrastim may be administered less frequently and may shorten the period of severe neutropenia in comparison to filgrastim; sargramostim may also be used
111
What is not an ADR associated with myeloid growth factors, according to the DSA?
No evidence that myeloid growth factors reduce the rate of remission or increase relapse rate in patients with myeloid or lymphoblastic leukemia (concern based on the fact that leukemic cells arise from progenitors regulated by HGFs including G-CSF and GM-CSF)\*
\*Actually controversial to untrue, check UpToDate, but know this for the test
112
In addition to cancer chemotherapy-induced neutropenia, what are some other applications for myeloid growth factors?
1. Treatment of neutropenia associated with congenital neutropenia, cyclic neutropenia, myelodysplasia, and aplastic anemia
2. May be combined with other growth factors for treatment of pancytopenia
3. Autologous stem cell transplantation in patients undergoing high-dose chemotherapy
1. Mobilizes PBSCs for collection by leukapheresis prior to chemotherapy
4. Reduces time to engraftment and to recovery from neutropenia after chemotherapy and reinfusion of PBSCs (or bone marrow stem cells)
113
What are megakaryocyte growth factors indicated for?
Patients with thrombocytopenia have a high risk of hemorrhage
114
What are endogenous regulators of platelet production?
Thrombopoietin and interleukin-11 (IL-11) are endogenous regulators of platelet production
115
Does recombinant thrombopoietin exist?
No - recombinant thrombopoietin cannot be used clinically due to production of autoantibodies that result in development of thrombocytopenia
116
What is oprelvekin? How is it made?
**Oprelvekin** is the recombinant form of IL- 11 approved for clinical use; produced by expression in *Escherichia coli*
117
What is the half life and ROA for oprelvekin?
Half-life is 7-8 hours when injected SubQ
118
What is the MOA for oprelvekin?
activates specific cell surface cytokine receptors to stimulate the growth of multiple lymphoid and myeloid cells;
acts synergistically with other growth factors to stimulate the growth of primitive megakaryocytic progenitors;
increases the number of peripheral platelets and neutrophils
119
What is romiplostim?
peptide agonist of the thrombopoietin receptor, Mpl
Member of a new class of therapeutics called peptibodies, which are peptides with key biologic activities covalently linked to antibody fragments that serve to extend the peptide’s half-life
120
What is the MOA for romiplostim?
**MOA**: activates Mpl thrombopoietin receptor to cause a dose-dependent increase in platelet count that begins 5 days after SubQ injection and peaks at 12-15 days
121
What is the half life and ROA for romiplostim?
Half-life is 3-4 days after SubQ injection;
half-life is inversely related to serum platelet count
122
What is IL-11 approved for?
IL-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for nonmyeloid cancers; reduces the number of platelet transfusions
123
What is romiplostim approved for?
Romiplostim is approved for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia purpura (ITP) who have had insufficient response to corticosteroids, immune globulin, or splenectomy
124
What are the toxicities associated with IL-11?
Fatigue, headache, dizziness, and cardiovascular effects (e.g., anemia, dyspnea, transient atrial arrhythmias) are the most common
Hypokalemia
All adverse effects are reversible
125
What are the toxicities associated with romiplostim?
Well tolerated except for a mild headache on the day of administration
126
