Anemias and Sickle Cell (Exam 1) Flashcards
Anemia
Too few RBCs, either by destruction or loss
Symptoms of Anemia
Fatique
Tachypnea & dyspnea
Tachycardia
Pallor & cold extremities
Hemoglobin (HgB) levels in Anemic Males
HgB <13.5 g/dL
Hemoglobin (HgB) levels in Anemic Females
HgB <12 g/dL
What causes anemia? (3)
Impaired erythrocyte production
Blood Loss
Increased erythrocyte destruction
How is anemia classified?
Effect on RBC size determined by mean corpuscular volume (MCV)
Microcytic Anemia
<80 fL MCV
Decreased hemoglobin production
Microcytic Anemia Subtypes (4)
Iron deficiency
Sideroblastic
Chronic Inflammation
Thalassemias
Normocytic Anemia
80-100 fL
Bleeding, hemolysis
Bone marrow suppression, chronic kidney disease
Normocytic Anemia Subtypes (2)
Loss of RBC
Decreased RBC production
Macrocytic Anemia
> 100 fL
Decreased DNA production
Macrocytic Anemia Subtype (2)
Megaloblastic
Non-megaloblastic
What is the most common type of anemia?
Microcytic, hypochromic anemia
Heme Iron
Absorbed by GI transporter
Found in meat
Non-Heme Iron
Exists as Fe3+
Trivalent, ferric state
Ferrireductase
Reduces Fe3+ to Fe2+ prior to absorbtion
What is the co-factor for ferrireductase?
Vitamin C
Relationship between non-heme iron and absorption
Lower pH = more absorption
What are the two most common routes of administration for iron?
Oral and IV
Why is Fe2+ used instead of Fe3+?
Higher bioavailability
Ferrous sulfate, hydrated
Size: 325mg
Iron: 65mg
Dosing: 2-4 tabs per day
Ferrous sulfate, desiccated
Size: 200mg
Iron: 65mg
Dosing: 2-4 tabs per day
Ferrous gluconate
Size: 325mg
Iron: 36mg
Dosing: 3-4 tabs per day
Ferrous fumarate
Size: 325mg
Iron: 106mg
Dosing: 2-3 tabs per day
Why would one use ferrous gluconate over ferrous sulfate?
Patient has GI problems
No differences in bioavailability so it’s interchangeable
Why is it recommended to take oral iron supplements on an empty stomach?
Maximize absorption since gastric pH is lower before eating
DMT1 Transporter
Non specific transporter that binds iron
Relationship between DMT1 binding and absorption
Drugs that bind to DMT1 transporter can decrease absorption of Fe
GI ADRs (4)
Stomach cramping
Heartburn
Constipation
Black tarry stools
What are GI ADRs from?
Free radical generation
Changes to gut microbiota
Acute iron toxicity symptoms
Bleeding, vomiting, diarrhea, dyspnea, coma
Intravenous deferoxamine (DFO)
Antidote for iron overdose
Iron chelator which increases iron excretion
What state is parenteral given?
The Fe3+ state
Binds to transferrin
What is the challenge with giving iron through IV?
Unbound iron in the blood is toxic
ADR associated with IV iron
Hypersensitivity reactions
Vitamin B12
Cobalamin
What does vitamin B12 deficiency cause?
Macrocytic, megaloblastic anemia
Reduces DNA synthesis
Reduction of DNA synthesis
Impairs cell division leading to megaloblasts
Vitamin B12 Absorption
Requires acidic environment and intrinsic factor
Pernicious Anemia
Defective absorption
High gastric pH, antibodies against intrinsic factor
Symptoms of Vitamin B12 Deficiency
Paresthesia, weakness, cognitive impairment
Due to myelin abnormalities
Why is parenteral injection of B112 the most common?
Deficiency is caused by poor absorption
What does folate (vitamin B9) deficiency cause?
Macrocytic, megaloblastic anemia
Reduces DNA synthesis
Folic Acid
Synthetic form of folate used in supplements and fortified foods
Used because it’s heat and light stable
5-MTHF
Reduction and methylation turns folic acid into 5-MTHF
ADRs of Folic Acid
Mild nausea, abdominal pain, bloating
Erythropoietin stimulating agents (ESAs) mimic…?
Endogenous EPO
Chronic Kidney Diseases
Anemia occurs due to a reduction in EPO production
Drug Induced Anemias
Some drugs cause myelosuppression
Epoetin
Recombinant human EPO
Darbepoetin
Synthetic EPO analogue
Prolongs half life
ESAs Mechanism of Action
Agonists at EPO receptors on hemopoietic cells in bone marrow resulting in increased RBC production
ESAs through subcutaneous administration
Increases half life
Darbepoetin»_space; Epoetin
ADRs for ESAs
Increased risk for cardiovascular thrombotic events
Increased blood pressure
When should ESAs be used?
Hgb <10g/dL with intent to prevent need for blood transfusion
ESA is not effective if…
Iron levels are low
Iron is important cofactor
Sickle Cell Disease
Genetic disorder caused by DNA mutation leading to production of defective beta globin chains
HbS
Sickling occurs when…
HbS is deoxygenated
Normal hemoglobin vs Sickle-cell
Normal: Negatively charged Glutamate
Sickle-cell: Neutral Valine
Electrophoretic Patterns
Normal: BaBa
Sickle-cell trait: BaBS
Sickle-cell anemia: BSBS
Pathophysiology of Sickle-Cell Disease
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
Medications preventing vaso-occlusion
Hydroxyurea
L-glutamine
Crizanlizumab
Voxelotor
Mediactions for infection prevention and treatment
Penicillin prophylaxis
Vaccinations
Hydroxyurea treatment
MoA increases gamma globin production and HbF
ADRs of hydroxyurea
Immunosuppression, myelosuppression, gastrointestinal issues
L-glutamine treatment
MoA decreases oxidative stress
Improves ratio of NADH to NADtotal
5-15g
Oral
BID
Crizanlizumab treatment
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
Voxelotor treatment
HbS polymerization inhibitor
Binds reversibly to hemoglobin preventing polymerization and increasing hemoglobin affinity for oxygen
1500mg
Oral
QD
PK consideration for voxelotor
Drug interactions with CYP3A4 inhibitors and inducers
