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PHA6126 Pharmacology 2 Lecture > Agents used in Anemias and Hematopoietic Growth Factors > Flashcards

Agents used in Anemias and Hematopoietic Growth Factors Flashcards

1
Q

Condition caused by a lack of RBCs which supply oxygen to different parts of the body

A

Anemia

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2
Q

Possible causes of Anemia

A
  1. low iron
  2. low folic acid & vit. B12
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3
Q

Essential component of hemoglobin

A

Iron

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4
Q

Essential for the maturation of cells

A

Folic acid & Vitamin B12

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5
Q

Formation of blood cells

A

Hematopoiesis

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6
Q

Drugs involved in the formation of blood cells

A

Hematopoietic drugs

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7
Q

Need growth factors or stimulating factors

A

Hematopoietic Stem Cells (HSC)

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8
Q

Other term for HSC

A

Hemocytoblasts

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9
Q

Capable of producing different types of cells which are pluripotent

A

Hematopoietic Stem Cells (HSC)

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10
Q

Refers to the ability of HSCs to renew on its own

A

Pluripotent

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11
Q

Cells that arise from HSC

A
  1. Lymphoid progenitor
  2. Myeloid progenitor
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12
Q

Arise from lymphoid progenitor

A

Lymphoblasts

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13
Q

Arise from lymphoblasts

A
  1. T-lymphocytes
  2. B-lymphocytes
  3. Natural killer cells
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14
Q

Cells that arise from myeloid progenitor

A
  1. Erythrocyte
  2. Megakaryocyte
  3. Myeloblast
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15
Q

Arise from myeloblast

A
  1. Monocyte
  2. Neutrophil
  3. Basophil
  4. Eosinophil
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16
Q

Gives rise to Macrophage

A

Monocyte

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17
Q

Fights bacterial infection

A

Neutrophil

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18
Q

Carries oxygen

A

Erythrocyte

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19
Q

Fights helminthic infection

A

Eosinophil

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20
Q

Gives rise to platelets

A

Megakaryocyte

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21
Q

Forms clots to stop bleeding

A

Platelets

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22
Q

Release in response to worms and environmental threats

A

Basophil

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23
Q

Deficiency in erythrocytes

A

Anemia

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24
Q

Deficiency in platelet

A

Thrombocytopenia

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25
Q

Deficiency in neutrophil

A

Neutropenia

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26
Q

Normal color of RBCs

A

Normochromic

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27
Q

Paler than normal RBCs

A

Hypochromic

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28
Q

Normal sized RBCs

A

Normocytic

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29
Q

Smaller sized RBCs

A

Microcytic

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30
Q

Larger size RBCs

A

Macrocytic

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31
Q

Large and immature cells

A

Megaloblastic

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32
Q

Rate of cell destruction

A

Hemolysis

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33
Q

Normal range of WBCs

A

3,500-11,000 cells/mcL

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34
Q

Normal range of hematocrit for women

A

34.9%-44.5%

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35
Q

Normal range of hematocrit for men

A

38.8%-50.0%

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36
Q

Normal range of platelets count

A

150,000-450,000/mcL

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37
Q

Normal range of RBCs in women

A

3.9-5.1 million cells/mcL

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38
Q

Normal range of RBCs in men

A

4.3-5.7 million cells/mcL

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39
Q

Normal range of hemoglobin in men

A

13-17 g/dL

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40
Q

Normal range of hemoglobin in women

A

11.5-15.5 g/dL

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41
Q

5 Types of Anemia

A
  1. Sickle cell
  2. Iron deficiency
  3. Aplastic
  4. Thalassemia
  5. Vitamin Deficiency
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42
Q

Genetic disorder wherein the erythrocytes is shaped like crescent moon

A

Sickle cell

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43
Q

Most common type of anemia

A

Iron deficiency

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44
Q

Occurs when the body stops producing enough new blood

A

Aplastic

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45
Q

Inherited blood disorder that causes the blood to have less hemoglobin

A

Thalassemia

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46
Q

Lack of healthy blood cell caused by a deficiency in Vitamin B12 and folate

A

Vitamin Deficiency

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47
Q

3 Possible causes of Anemia

A
  1. malabsorption of RBCs
  2. hemolysis of RBCs
  3. increased demand for RBCs
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48
Q

Forms the nucleus of iron-porphyrin heme which together with globulin chains form hemoglobin

A

Iron

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49
Q

How is hemoglobin formed?

A

Fe-porphyrin heme + protein (globulin)

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50
Q

Indicated for the tx or prevention of IDA

A

Iron

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51
Q

Manifest as hypochromic, microcytic anemia

A

Iron Deficiency Anemia (IDA)

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52
Q

Commonly seen in infants, children during rapid growth, pregnant and lactating women and CKD patients undergoing dialysis

A

IDA

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53
Q

more absorbable source of iron in animals

A

heme

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54
Q

source of iron in plants

A

non-heme

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55
Q

Site of blood formation

A

bone marrow

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56
Q

produce the erythropoietin hormone needed for the formation of RBCs

A

kidneys

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57
Q

transported by heme carrier protein (HCP)

A

Heme

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58
Q

transported by divalent metal transporter (DMT)

A

Non-heme

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59
Q

Heme carrier protein (HCP) → Ferroportin (FP) → bloodstream

A

Heme Pathway

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60
Q

Divalent metal transporter (DMT) → Apoferritin (AF) will complex with ferrous → FP → bloodstream

A

Non-Heme Pathway

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61
Q

attach to the receptor in the bone marrow

A

Transferrin (Tf)

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62
Q

The following process occurs where?

Tf → release ferrous → mix to form hemoglobin

A

Bloodstream

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63
Q

stored in the liver

A

Ferritin

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64
Q

most efficiently absorbed iron in oral iron therapy

A

Ferrous (II) iron

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65
Q

Other types of oral iron therapy for anemia

A

Ferrous sulfate, Ferrous gluconate and Ferrous fumarate

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66
Q

About _____________________ given as ferrous salt can be absorbed

A

25% of oral iron

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67
Q

About 25% of oral iron given as ______________ can be absorbed

A

ferrous salt

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68
Q

Common ADRs of oral iron therapy

A
  1. Nausea
  2. Epigastric discomfort
  3. Abdominal cramps
  4. Constipation
  5. Diarrhea
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69
Q

Major side effect of iron

A

Gastric toxicity

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70
Q

Patients unable to tolerate large amount of iron may be given _______________________

A

lower daily dose of iron

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71
Q

Absorbed iron

A

Elemental iron

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72
Q

Elemental iron content of Ferrous sulfate, hydrated

A

65 mg

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73
Q

Elemental iron content of Ferrous sulfate, desiccated

A

65 mg

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74
Q

Elemental iron content of Ferrous gluconate

A

36 mg

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75
Q

Elemental iron content of Ferrous fumarate

A

106 mg

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76
Q

Tablet size of commonly used oral iron preparations (ferrous sulfate, ferrous gluconate, & ferrous fumarate)

A

325 mg

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77
Q

Usual adult dose of tx using ferrous sulfate hydrated & desiccated

A

2-4 tablets per day

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78
Q

Usual adult dose of tx using ferrous gluconate

A

3-4 tablets per day

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79
Q

Usual adult dose of tx using ferrous fumarate

A

2-3 tablets per day

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80
Q

Reserved for patients with iron deficiency who can not tolerate oral iron

A

Parenteral Iron

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81
Q

Reserved for patients with advance CKD requiring hemodialysis & treatment with erythropoietin

A

Parenteral iron

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82
Q

Reserved for patients with various post gastrectomy condition and previous small bowel resection, inflammatory bowel disease

A

Parenteral iron

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83
Q

Can produce serious dose dependent toxicity

A

Parenteral iron

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84
Q

Types of Parenteral iron

A

Iron Dextran, Sodium Ferric Gluconate Complex, Iron Sucrose Complex

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85
Q

Stable complex or ferric oxyhydroxide and dextran polymer containing 50mg elemental iron/mL of solution

A

Iron dextran

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86
Q

Iron dose is also known as _________

A

Elemental iron

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87
Q

Iron dextran is composed of?

A

ferric oxyhydroxide and dextran polymer

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88
Q

Given by deep IM or IV infusion

A

Iron dextran

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89
Q

Colloidal Iron preparation with carbohydrate polymer

A

Ferric carboxymaltose

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90
Q

Superparamagnetic iron oxide nanoparticle coated with carbohydrate that may interfere with MRI

A

Ferumoxytol

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91
Q

Only given by IV route

A

Sodium Ferric Gluconate Complex and Iron Sucrose Complex

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92
Q

Monitoring iron storage level to avoid serious toxicity is done for _____________________

A

patients treated chronically parenteral iron

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93
Q

What must be done for patients treated with chronically parenteral iron?

A

Monitor iron storage level

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94
Q

Why must iron storage level be monitored for patients treated with chronically parenteral iron?

A

To avoid serious toxicity

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95
Q

Almost exclusive in young children

A

Acute Iron Toxicity

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96
Q

10 tablets can be lethal in young children

A

Acute Iron Toxicity

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97
Q

Children poisoned with oral iron may experience

A

Necrotizing gastroenteritis with vomiting, abdominal pain, bloody diarrhea

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98
Q

Flush unabsorbed pills

A

Whole bowel Irrigation

99
Q

Antidote for iron toxicity

A

Deferoxamine

100
Q

Potent chelating agent in which excess iron will combine with this drug and is excreted through urine

A

Deferoxamine

101
Q

Hemochromatosis

A

Chronic Iron Toxicity

102
Q

Excess iron may be deposited in the heart, liver, pancreas and other organs

A

Chronic Iron Toxicity

103
Q

Most commonly occur in patients with inherited hemochromatosis

A

Chronic Iron Toxicity

104
Q

Iron chelating therapy with parenteral deferoxamine or oral iron chelator is less efficient

A

Chronic Iron Toxicity

105
Q

Antidote for Chronic Iron Toxicity

A

Phlebotomy

106
Q

serves as a cofactor for several essential biochemical reaction

A

Cobalamin or Vit. B12

107
Q

Vit. B12 deficiency leads to

A
  1. Megaloblastic anemia
  2. Gastrointestinal symptoms
  3. Neurologic abnormalities
108
Q

abnormal sensation, cause ataxia, weakness and spasticity

A

Paresthesia

109
Q

disorder that affect coordination and balance

A

Ataxia

110
Q

Active forms of the vitamin B12 in humans

A

Deoxyadenosylcobalamin and Methylcobalamin

111
Q

Naturally-occuring forms of vitamin B12

A

Deoxyadenosylcobalamin and Methylcobalamin

112
Q

Available for therapeutic use

A

Cyanocobalamin and Hydroxycobalamin

113
Q

Synthetic forms of vitamin B12

A

Cyanocobalamin and Hydroxycobalamin

114
Q

Stable and most effective form of vit. B12 but must be converted to the active form

A

Cyanocobalamin

115
Q

Ultimate source of Vit. B12

A

microbial synthesis

116
Q

needs to bind with intrinsic factor (secreted by GI) to be absorbed

A

Extrinsic factor

117
Q

Average American Diet of Vit. B12

A

5-30 mcg of Vit. B12

118
Q

Absorbed Vit. B12

A

1-5 mcg

119
Q

Recommended daily allowance of Vit. B12

A

2-2.4 mcg

120
Q

released by salivary glands to separate vit. B12 and dietary protein

A

Haptocorrin

121
Q

a protein released by the stomach to bind with vit. B12, aiding its absorption

A

Intrinsic factor

122
Q

Illium contains this receptor which specializes in the absorption of vit. B12 resulting in the separation of vit. B12 and IF

A

Cubam receptor

123
Q

Transport vit. B12 to bloodstream of the cell

A

Transcobalamin

124
Q

2 essential enzymatic reaction in humans associated with vit. B12

A
  1. Methyltransfer from N5-methyltetrahydrofolate
    to homocysteine
  2. Isomerization of L-Methylmalonyl CoA
125
Q

precursor of different biochemical reactions

A

Methyltransfer from N5-methyltetrahydrofolate
to homocysteine

126
Q

Manifestation of Vit B12 deficiency

A
  1. Megaloblastic, macrocytic anemia
  2. Often associated mild or moderate leukopenia or thrombocytopenia
  3. Neurological syndrome
127
Q

low leukocytes

A

leukopenia

128
Q

Correction of vit. B12 deficiency _________________________ of neurologic disease it may not fully reverse neurologic symptoms

A

arrest the progression

129
Q

Correction of vit. B12 deficiency arrest the progression of neurologic disease it ____________________________ neurologic symptoms

A

may not fully reverse

130
Q

measures the absorption & urinary excretion of radioactively labeled vit. B12

A

Schilling test

131
Q

Defective secretion of intrinsic factor by the gastric mucosal cell

A

Pernicious anemia

132
Q

available as cyanocobalamin or hydroxycyanocobalamin

A

Vitamin B12 parenteral injection

133
Q

Initial dose of Vitamin B12 parenteral injection

A

100 – 1000mcg vit B12 IM daily or every other day for 1 – 2 weeks

134
Q

Maintenance dose of Vitamin B12 parenteral injection

A

100 – 1000mcg IM once a month for life

135
Q

Very important for pregnancy as it is needed for the baby’s brain and spinal cord development

A

Folic acid

136
Q

result of inadequate folic acid during pregnancy

A

Neural tube defect

137
Q

required for essential biochemical reaction that provides precursors for the synthesis of amino acid, purine and DNA

A

reduced form of folic acid

138
Q

cause of congenital malformation in newborns

A

Folate deficiency

139
Q

Play an important role in vascular disease

A

Folic acid

140
Q

undergoes reduction, catalyzed by the enzyme dihydrofolate reductase to give dihydrofolic acid

A

Folic acid

141
Q

Enzyme that catalyzes folic acid, giving rise to dihydrofolic acid

A

dihydrofolate reductase

142
Q

Average American Folic Acid diet

A

500-700 mcg folate daily

143
Q

Folate absorbed

A

50-200 mcg

144
Q

Folate absorbed by pregnant women

A

300-400 mcg daily

145
Q

excreted in urine and stool

A

Folic acid

146
Q

readily and completely absorbed in the proximal jejunum

A

Unaltered folic acid

147
Q

Folate deficiency results in

A

Megaloblastic anemia

148
Q

Patients with alcohol dependence and patients with liver disease can develop

A

folic acid deficiency

149
Q

Folic acid deficiency can develop in pregnant women and patients with ________________________

A

hemolytic anemia

150
Q

Folic acid deficiency can also develop in patients who require __________________

A

renal dialysis

151
Q

Dose and frequency sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients

A

1 mg folic acid orally daily

152
Q

Glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow

A

Hematopoietic Growth Factor

153
Q

Stimulate the growth of colonies of various bone marrow progenitor cells in vitro

A

Colony Stimulating Factor (CSF)

154
Q

for neutrophil, basophil, and eosinophil

A

Granulocyte colony stimulating factor (G-CSF)

155
Q

typically given for neutrophil deficiency

A

Granulocyte colony stimulating factor (G-CSF)

156
Q

First human hematopoietic growth factor to be isolated

A

Erythropoietin

157
Q

Originally purified from the urine of patients with severe anemia

A

Erythropoietin

158
Q

Produced in a mammalian cell expression system

A

Recombinant human erythropoietin (rHuEPO, Epoetin Alpha)

159
Q

Half-life after IV admin of rHuEPO in px with chronic kidney failure

A

4-13 hours

160
Q

Not cleared by dialysis

A

Recombinant human erythropoietin (rHuEPO, Epoetin Alpha)

161
Q

Administered thrice a week

A

Recombinant human erythropoietin (rHuEPO, Epoetin Alpha)

162
Q

Given once a week

A

Darbepoetin alpha

163
Q

Modified form of erythropoietin that is more heavily glycosylated as a result of changes in amino acid

A

Darbepoetin alpha

164
Q

Has two-fold to three-fold longer half-life than epoetin alpha

A

Darbepoetin alpha

165
Q

Isoform of erythropoietin covalently attached to a longer polyethylene glycol polymer

A

Methoxy polyethylene glycol – epoetin

166
Q

Long lived recombinant product is administered as a single intravenous or subcutaneous dose at 2 week or monthly intervals

A

Methoxy polyethylene glycol – epoetin

167
Q

Stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptor on the RBC progenitor

A

Erythropoietin

168
Q

Induces the release of reticulocyte from the bone marrow

A

Erythropoietin

169
Q

Immature RBC from the bone marrow

A

reticulocyte

170
Q

primarily produced in the kidney

A

Endogenous erythropoietin

171
Q

In response to _______________, more erythropoietin is produced through an increased rate of transcription of the erythropoietin gene

A

tissue hypoxia

172
Q

Low hematocrit, low hemoglobin, and high erythropoietic results in

A

Anemia

173
Q

consistently improve the hematocrit and hemoglobin level, often the need for transfusion

A

Erythropoiesis – stimulating agents (ESA)

174
Q

Used routinely in patients with anemia secondary to CKD

A

Erythropoietin-Stimulating agent

175
Q

T/F: Erythropoietin-Stimulating agent dose should not exceed 10-12 g/dL

A

True

176
Q

T/F: Erythropoietin-Stimulating agent increase the need for RBC transfusion in px undergoing myelosuppressive cancer chemotherapy who have hemoglobin of less than 5g/dL.

A

False; reduce the need…hemoglobin of less than 10g/dL

177
Q

Most commonly observed HTN and thrombic complication

A

Erythropoietin-Stimulating agent toxicity

178
Q

Myeloid Growth Factor drugs

A
  1. Recombinant Human G-CSF (rHuG-CSF; Filgrastim)
  2. Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)
  3. Pegfilgrastim
  4. Lenograstim
179
Q

used for patients with neutropenia

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

180
Q

Produced by bacterial expression system

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

181
Q

Non-glycosylated peptide of 175 amino acid with a molecular weight of 18KDa

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

182
Q

Stimulates the proliferation and differentiation of progenitor already committed to the neutrophil lineage

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

183
Q

Activates the phagocytic activity of mature neutrophil and prolongs their survival in the circulation

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

184
Q

Recombinant Human G-CSF (rHuG-CSF; Filgrastim) Dose

A

5 mcg/kg/day

185
Q

Recombinant Human G-CSF (rHuG-CSF; Filgrastim) toxicity

A

Minimal but may cause bone pain

186
Q

Given for cancer related disease(s) before chemotherapy

A

Recombinant Human G-CSF (rHuG-CSF; Filgrastim)

187
Q

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim) Half-life of IV or SC

A

2-7 hours

188
Q

Has broader biological activity that G-CSF

A

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)

189
Q

Stimulates the function of mature neutrophils

A

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)

190
Q

Less efficacious and more toxic than G-CSF

A

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)

191
Q

Reduces the duration of neutropenia after cytotoxic chemotherapy

A

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)

192
Q

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim) Dose

A

250 mcg/m2/day

193
Q

May cause anaphylactic shock, arthralgias and capillary leak (causing peripheral edema)

A

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim)

194
Q

Recombinant human GM-CSF (rHuGM-CSF; Sargramostim) at high doses

A

Severe effect

195
Q

Covalent conjunction product of filgrastim and a form of polyethylene glycol

A

Pegfilgrastim

196
Q

longer serum half-life than recombinant G-CSF

A

Pegfilgrastim

197
Q

Can be injected once per myelosuppressive chemotherapy cycle instead of daily for several days

A

Pegfilgrastim

198
Q

Alternative for G-CSF

A

Pegfilgrastim

199
Q

for prevention of chemo induced febrile neutropenia

A

Pegfilgrastim

200
Q

May shorten the period of severe neutropenia slightly more than G-CSF

A

Pegfilgrastim

201
Q

Pegfilgrastim Dose

A

Single dose of 6 mg

202
Q

Glycosylated form of recombinant G-CSF

A

Lenograstim

203
Q

For patients with thrombocytopenia

A

Megakaryocyte Growth Factor

204
Q

Commonly used to treat thrombocytopenia

A

Platelet transfusion

205
Q

Thrombopoietin (TPO) and Interleukin-11

A

Megakaryocyte Growth Factor

206
Q

Produced fibroblast and stromal cell of the bone marrow

A

Interleukin - 11

207
Q

Acts through a specific cell surface cytokine receptor to stimulate the growth of multiple lymphoid and myeloid cell

A

Interleukin - 11

208
Q

Acts synergistically with other growth factors to stimulate growth and proliferation of primitive megakaryocyte progenitor

A

Interleukin - 11

209
Q

Half-life of Interleukin - 11 when administered SQ

A

7-8 hours

210
Q

for secondary prevention of thrombocytopenia

A

Interleukin - 11

211
Q

Reduces the number of platelet transfusion required

A

Interleukin - 11

212
Q

Interleukin - 11 Dose

A

50 mcg/kg/day

213
Q

Starts 6-24 hours after completion of chemo & continued for 14-21 days

A

Interleukin - 11

214
Q

Recombinant form of IL-11

A

Oprelvekin

215
Q

Produced by expression of E. coli

A

Oprelvekin

216
Q

Recombinant thrombopoietin

A

Romiplostim

217
Q

Peptide covalently linked to antibody fragment which extends the peptides T1/2

A

Romiplostim

218
Q

After SQ, Romiplostim is eliminated by ___________________

A

reticuloendothelial system

219
Q

Average half-life of Romiplostim SQ

A

3-4 days

220
Q

Relationship of Romiplostim half-life and serum platelet count

A

inversely related

221
Q

In patients with thrombocytopenia, Romiplostim has a _____________ (longer/shorter) half-life

A

longer

222
Q

only oral preparation of Megakaryocyte Growth Factor

A

Eltrombopag

223
Q

For chronic immune thrombocytopenia and thrombocytopenia in patients with Hepa C

A

Eltrombopag

224
Q

Eltrombopag mode of administration

A

Oral

225
Q

Eltrombopag half-life

A

26-35 hours

226
Q

Eltrombopag peaks

A

2-6 hours

227
Q

Potentially hepatotoxic

A

Eltrombopag

228
Q

Increases the blast count and risk of progression to acute myeloid leukemia

A

Romiplostim

229
Q

Increase risk of clot formation

A

Romiplostim

230
Q

Recombinant G-CSF

A

Filgrastim

231
Q

Recombinant GM-CSF

A

Sargramostim

232
Q

Recombinant thrombopoietin

A

Romiplostim

233
Q

Thrombopoietin Agonist

A

Eltrombopag

234
Q

Recombinant human Erythropoietin

A

Epoeitin alpha

235
Q

Epoeitin alpha Route of Admin

A

IV

236
Q

Eltrombopag Route of Admin

A

Oral

237
Q

Sargramostim Route of Admin

A

IV or SC

238
Q

Filgrastim Route of Admin

A

IV or SC

239
Q

Romiplostim Route of Admin

A

SC

240
Q

Epoetin alpha Use

A

Anemia

241
Q

Eltrombopag Use

A

Thrombocytopenia

242
Q

Sargramostim Use

A

Neutropenia

243
Q

Filgrastim Use

A

Neutropenia

244
Q

Romiplostim

A

Thrombocytopenia

PHA6126 Pharmacology 2 Lecture (10 decks)

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