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Pharmacology > Anemias and Sickle Cell (Exam 1) > Flashcards

Anemias and Sickle Cell (Exam 1) Flashcards

1
Q

Anemia

A

Too few RBCs, either by destruction or loss

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2
Q

Symptoms of Anemia

A

Fatique
Tachypnea & dyspnea
Tachycardia
Pallor & cold extremities

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3
Q

Hemoglobin (HgB) levels in Anemic Males

A

HgB <13.5 g/dL

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4
Q

Hemoglobin (HgB) levels in Anemic Females

A

HgB <12 g/dL

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5
Q

What causes anemia? (3)

A

Impaired erythrocyte production
Blood Loss
Increased erythrocyte destruction

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6
Q

How is anemia classified?

A

Effect on RBC size determined by mean corpuscular volume (MCV)

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7
Q

Microcytic Anemia

A

<80 fL MCV
Decreased hemoglobin production

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8
Q

Microcytic Anemia Subtypes (4)

A

Iron deficiency
Sideroblastic
Chronic Inflammation
Thalassemias

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9
Q

Normocytic Anemia

A

80-100 fL
Bleeding, hemolysis
Bone marrow suppression, chronic kidney disease

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10
Q

Normocytic Anemia Subtypes (2)

A

Loss of RBC
Decreased RBC production

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11
Q

Macrocytic Anemia

A

> 100 fL
Decreased DNA production

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12
Q

Macrocytic Anemia Subtype (2)

A

Megaloblastic
Non-megaloblastic

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13
Q

What is the most common type of anemia?

A

Microcytic, hypochromic anemia

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14
Q

Heme Iron

A

Absorbed by GI transporter
Found in meat

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15
Q

Non-Heme Iron

A

Exists as Fe3+
Trivalent, ferric state

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16
Q

Ferrireductase

A

Reduces Fe3+ to Fe2+ prior to absorbtion

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17
Q

What is the co-factor for ferrireductase?

A

Vitamin C

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18
Q

Relationship between non-heme iron and absorption

A

Lower pH = more absorption

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19
Q

What are the two most common routes of administration for iron?

A

Oral and IV

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20
Q

Why is Fe2+ used instead of Fe3+?

A

Higher bioavailability

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21
Q

Ferrous sulfate, hydrated

A

Size: 325mg
Iron: 65mg
Dosing: 2-4 tabs per day

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22
Q

Ferrous sulfate, desiccated

A

Size: 200mg
Iron: 65mg
Dosing: 2-4 tabs per day

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23
Q

Ferrous gluconate

A

Size: 325mg
Iron: 36mg
Dosing: 3-4 tabs per day

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24
Q

Ferrous fumarate

A

Size: 325mg
Iron: 106mg
Dosing: 2-3 tabs per day

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25
Q

Why would one use ferrous gluconate over ferrous sulfate?

A

Patient has GI problems
No differences in bioavailability so it’s interchangeable

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26
Q

Why is it recommended to take oral iron supplements on an empty stomach?

A

Maximize absorption since gastric pH is lower before eating

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27
Q

DMT1 Transporter

A

Non specific transporter that binds iron

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28
Q

Relationship between DMT1 binding and absorption

A

Drugs that bind to DMT1 transporter can decrease absorption of Fe

29
Q

GI ADRs (4)

A

Stomach cramping
Heartburn
Constipation
Black tarry stools

30
Q

What are GI ADRs from?

A

Free radical generation
Changes to gut microbiota

31
Q

Acute iron toxicity symptoms

A

Bleeding, vomiting, diarrhea, dyspnea, coma

32
Q

Intravenous deferoxamine (DFO)

A

Antidote for iron overdose
Iron chelator which increases iron excretion

33
Q

What state is parenteral given?

A

The Fe3+ state
Binds to transferrin

34
Q

What is the challenge with giving iron through IV?

A

Unbound iron in the blood is toxic

35
Q

ADR associated with IV iron

A

Hypersensitivity reactions

36
Q

Vitamin B12

A

Cobalamin

37
Q

What does vitamin B12 deficiency cause?

A

Macrocytic, megaloblastic anemia
Reduces DNA synthesis

38
Q

Reduction of DNA synthesis

A

Impairs cell division leading to megaloblasts

39
Q

Vitamin B12 Absorption

A

Requires acidic environment and intrinsic factor

40
Q

Pernicious Anemia

A

Defective absorption
High gastric pH, antibodies against intrinsic factor

41
Q

Symptoms of Vitamin B12 Deficiency

A

Paresthesia, weakness, cognitive impairment
Due to myelin abnormalities

42
Q

Why is parenteral injection of B112 the most common?

A

Deficiency is caused by poor absorption

43
Q

What does folate (vitamin B9) deficiency cause?

A

Macrocytic, megaloblastic anemia
Reduces DNA synthesis

44
Q

Folic Acid

A

Synthetic form of folate used in supplements and fortified foods
Used because it’s heat and light stable

45
Q

5-MTHF

A

Reduction and methylation turns folic acid into 5-MTHF

46
Q

ADRs of Folic Acid

A

Mild nausea, abdominal pain, bloating

47
Q

Erythropoietin stimulating agents (ESAs) mimic…?

A

Endogenous EPO

48
Q

Chronic Kidney Diseases

A

Anemia occurs due to a reduction in EPO production

49
Q

Drug Induced Anemias

A

Some drugs cause myelosuppression

50
Q

Epoetin

A

Recombinant human EPO

51
Q

Darbepoetin

A

Synthetic EPO analogue
Prolongs half life

52
Q

ESAs Mechanism of Action

A

Agonists at EPO receptors on hemopoietic cells in bone marrow resulting in increased RBC production

53
Q

ESAs through subcutaneous administration

A

Increases half life
Darbepoetin&raquo_space; Epoetin

54
Q

ADRs for ESAs

A

Increased risk for cardiovascular thrombotic events
Increased blood pressure

55
Q

When should ESAs be used?

A

Hgb <10g/dL with intent to prevent need for blood transfusion

56
Q

ESA is not effective if…

A

Iron levels are low
Iron is important cofactor

57
Q

Sickle Cell Disease

A

Genetic disorder caused by DNA mutation leading to production of defective beta globin chains
HbS

58
Q

Sickling occurs when…

A

HbS is deoxygenated

59
Q

Normal hemoglobin vs Sickle-cell

A

Normal: Negatively charged Glutamate
Sickle-cell: Neutral Valine

60
Q

Electrophoretic Patterns

A

Normal: BaBa
Sickle-cell trait: BaBS
Sickle-cell anemia: BSBS

61
Q

Pathophysiology of Sickle-Cell Disease

A

1.) After deoxygenation, HbS molecules polymerize to form bundles
2.) Bundles result in sickling which leads to vaso-occulaion and promotes ischemia-reperfusion injury
OR
3.) Hemolytic process enhanced to release heme from RBC breakdown
4.) Both 2 & 3 promote sterile inflammation

62
Q

Medications preventing vaso-occlusion

A

Hydroxyurea
L-glutamine
Crizanlizumab
Voxelotor

63
Q

Mediactions for infection prevention and treatment

A

Penicillin prophylaxis
Vaccinations

64
Q

Hydroxyurea treatment

A

MoA increases gamma globin production and HbF

65
Q

ADRs of hydroxyurea

A

Immunosuppression, myelosuppression, gastrointestinal issues

66
Q

L-glutamine treatment

A

MoA decreases oxidative stress
Improves ratio of NADH to NADtotal
5-15g
Oral
BID

67
Q

Crizanlizumab treatment

A

Monoclonal antibody for P-selectin
Blocks interaction with PSGL-1 and decreases vaso-occlusion
5mg/kg
IV infusion
Week 0, 2, then every 4 weeks

68
Q

Voxelotor treatment

A

HbS polymerization inhibitor
Binds reversibly to hemoglobin preventing polymerization and increasing hemoglobin affinity for oxygen
1500mg
Oral
QD

69
Q

PK consideration for voxelotor

A

Drug interactions with CYP3A4 inhibitors and inducers

Pharmacology (18 decks)

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