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Year 4 - Toxicology > 19 - Blood > Flashcards

19 - Blood Flashcards

1
Q

Vital functions of blood

A
  • Transport oxygen
  • Transport drugs
  • Maintain fluid balance
  • Important part of immune system
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2
Q

What is hematopoiesis? Where does it occur?

A
  • Occurs in bone marrow in healthy adults
  • Stem cells stimulated (poietins or colony-stimulating factors) to differentiate into committed cells that further mature
  • The earlier the drug-induced hematological disorder (DIHD) occurs in the cascade of hematopoiesis (differentiation) the more severe the disorder
  • Incidence of DIHD difficult to ascertain (0.01% drug-induced agranulocytosis)
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3
Q

Which drugs suppress bone marrow?

A
  • Methotrexate
  • Cyclophosphamide
  • Colchicine
  • Azathioprine
  • Ganciclovir
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4
Q

What are the types of hematoxicity?

A
  • Primary
  • Secondary
  • Idiosyncratic
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5
Q

What is primary hematotoxicity?

A

Direct cytotoxic mechanism or immunological mechanism

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6
Q

What is secondary hematotoxicity?

A
  • Toxic effect a consequence of other tissue injury or systemic disturbances
  • Damage caused by reactive/ compensatory mechanisms
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7
Q

Lab findings of anemia

A

Decreased RBC (count or volume) or decreased hemoglobin

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8
Q

Lab findings of polycythemia

A

Increased RBC (count or concentration)

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9
Q

Lab findings of thrombocytopenia

A

Decreased platelets

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10
Q

Lab findings of leukopenia

A

Decreased WBCs

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11
Q

Lab findings of granulocytopenia

A

Decreased neutrophils, eosinophils, and basophils

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12
Q

Lab findings of neutropenia

A

Decreased neutrophils

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13
Q

Lab findings of agranulocytosis

A

Very decreased neutrophils

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14
Q

Lab findings of pancytopenia

A

Decrease in all blood cells

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15
Q

Lab findings of hypocoagulability

A

Decreased clotting factors

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16
Q

What are the ways in which drugs may alter RBCs?

A
  • Production
  • Function
  • Survival
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17
Q

How can drugs alter RBC production?

A
  • Cell division/ hematopoiesis
  • Hemoglobin synthesis => iron deficiency anemia
  • Sideroblastic anemia
  • Megaloblastic anemia
  • Aplastic anemia
  • Polycythemia
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18
Q

How can drugs alter RBC function?

A
  • *Through effects on hemoglobin

- O2/ CO2 transport – shifts in oxygen dissociation curve => methemoglobinemia

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19
Q

How can drugs alter RBC survival?

A
  • Normally ~ 120 days but shortened by oxidative injury, decreased metabolism, and/ or altered membrane => hemolytic anemia (immune-mediated or oxidative injury such as G6PD deficiency)
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20
Q

What is sideroblastic anemia?

A

Interference w/ heme synthesis

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21
Q

Causes of sideroblastic anemia? Is it reversible?

A
  • EtOH
  • Isonizaid (w/o vitamin B6 supplementation)
  • Chloramphenicol
  • Cycloserine
  • Linezolid
  • Zinc toxicity/ copper deficiency
  • Lead intoxication
  • Reversible w/ drug d/c
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22
Q

What is megaloblastic anemia?

A

Abnormal development of RBC precursors (megaloblasts)

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23
Q

What can cause megaloblastic anemia?

A
  • Drugs w/ effect on DNA synthesis

- Folate and/or vitamin B12 deficiency from inadequate dietary intake or drugs

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24
Q

Which drugs have an effect on DNA synthesis?

A
  • Anti-neoplastics
  • Immunosuppressants
  • Allopurinol
  • Antiretrovirals
25
Which drugs cause folate and/or vitamin B12 deficiency?
- Drugs that inhibit dihydrofolate reductase (TMP-SMX) | - Drugs that inhibit folate or vitamin B12 absorption/ increase folate catabolism
26
Which drugs inhibit folate or vitamin B12 absorption and/or increase folate catabolism?
- Phenytoin, primidone, phenobarbital - Estrogens/ oral contraceptives - PPIs/H2RAs - Metformin - Antibiotics (penicillins, tetracyclines, erythromycin, nitrofurantoin)
27
What causes aplastic anemia?
- Bone marrow failure - Injury to pluripotent stem cell in bone marrow - Drugs, radiation, pregnancy, viruses, immune disorders, idiopathic
28
Which drugs cause aplastic anemia?
- Anti-neoplastics - Bismuth - Mercury - Sulfonamides - Carbamazepine - Gold compounds - Phenytoin - Benzene
29
Sx of aplastic anemia
- Fatigue, weakness - Stomatitis - Easy bruising - Petechiae - Purpura - Recurrent infections - Bleeding - Death (sepsis/ hemorrhage) w/in 18 months
30
Aplastic anemia treatment
- Withdrawal of drug - Symptomatic tx of bleeding, infection - Immunosuppressive -> corticosteroids, cyclosporine, GM-CSF, IL-1, GCSF, antithymocyte globulin - Bone marrow transplant
31
Sx of polycythemia
- Chest/ abdominal pain - Myalgia/ weakness/ fatigue - Headache - Paresthesias - Blurred vision/ transient loss of vision - Poor mentation/ sense of depersonalization - Risk of VTE
32
Mechanisms of polycythemia
- Increased erythropoiesis - Decreased plasma volume - Combination of both (ex: smoking, which causes chronic hypoxia)
33
Which drugs cause increased erythropoiesis?
- Cobalt - Blood doping, self-injection of erythropoietin - Testosterone (especially ester injections), anabolic steroids - Chronic/occupational exposure to CO
34
What is methemoglobin? Is the concentration normally high or low?
- Heme iron oxidized to ferric state, therefore cannot bind/ transport O2 - Normal control mechanisms maintain low methemoglobin concentration
35
What is methemoglobinemia?
- High methemoglobin concentration - Cyanosis appears when concentration > 5-10% - Life threatening at 70%
36
What causes methemoglobinemia?
- Oxidizing drugs | - Ex: nitrites, nitrates, nitroglycerin, topical anesthetics, street drugs
37
Antidote for methemoglobinemia? What does it do?
- Methylene blue | - Increases rate of methemoglobin reduction
38
Antidote for methemoglobinemia? What does it do?
- Methylene blue | - Increases rate of methemoglobin reduction
39
What is a hapten?
Small molecule that binds to larger carrier and elicits an immune response
40
Which drugs act as haptens?
- Beta lactams - Tetracyclines - Anti-neoplastics
41
Which drugs induce formation of auto-antibodies to cellular components?
- Levodopa, methyldopa - Procainamide - Cimetidine
42
Sx and onset of oxidative hemolysis
- Jaundice - Pallor - Dark urine - Onset = 2-4 days
43
What may cause oxidative hemolysis?
G6PD deficiency
44
What can cause myeloid leukemias?
- Alkylating agents (ex: melphalan, cyclophosphamide, busulfan, cisplatin) - Topoisomerase II inhibitors (ex: etoposide, doxorubicin, mitoxantrone) - Antimetabolites (ex: azathioprine, 6-mercaptopurine) - Radiation - Occupational exposure (benzene, formaldehyde) - Tobacco smoke
45
What can cause lymphoid leukemias?
- Radiation - Occupational exposure (paint, benzene, formaldehyde) - Tobacco smoke - Immunosuppression
46
Difference between neutrophils vs. basophils and eosinophils
- Neutrophils = mediate inflammation | - Basophils and eosinophils = modulate inflammation
47
Which drugs affect neutrophil proliferation?
- MTX - Cytarabine - Cyclophosphamide - Cisplatin
48
Which drugs impair phagocytosis of granulocytes?
- EtOH - Glucocorticoids - Radiocontrast dye
49
Is clozapine neutropenia immune mediated?
Yes
50
Many drugs that cause aplastic anemia can also cause ____
Toxic neutropenia/ agranulocytosis
51
What is agranulocytosis?
Neutrophils < 500/mm3
52
Clinical presentation of agranulocytosis
- Oral ulcers +/- fever - Severe pharyngitis, fever, malaise, weakness and chills - Sepsis
53
Tx of agranulocytosis
- D/c any drug associated w/ agranulocytosis - Symptomatic tx (infections) - IV immune globulin - G-CSF
54
What affect can drugs have on platelets?
- Alter quantity (either production or survival) - Alter activation - Alter function (ex: antiplatelets)
55
Clinical presentation of thrombocytopenia
- Early sx = bruising, petechiae/ ecchymosis, epistaxis - - May be initial manifestation of aplastic anemia - Fever, chills, pruritus, lethargy - Bleeding may be abrupt (life-threatening hemorrhage) - 7 days are required for the development of the immune response after the first exposure - Develops w/in 12 hours of a repeated exposure to a sensitizing agent
56
What is heparin-induced thrombocytopenia?
Platelet count < 150,000 cells/mm3
57
Types of heparin-induced thrombocytopenia
- Type 1 (non-immune) = early onset, non-thrombotic, self-limiting - Type 2 (immune) = delayed onset, unless previously sensitized
58
Tx of thrombocytopenia
- D/c the drug - - If HIT, start non-heparin anticoagulant (argatroban, DOACs) - - Anti-coagulate at least 2-3 months if no thrombosis, 3-6 months if thrombosis occurred - Transfusions - Immunosuppressive therapy
59
Tx for active bleeding w/ warfarin
- Hold warfarin | - Give IV vitamin K and factor concentrates

Year 4 - Toxicology (22 decks)

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