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DABT > Heme Tox C&D 8 > Flashcards

Heme Tox C&D 8 Flashcards

1
Q

11-1. What xenobiotics are associated with sideroblastic anemia (8)?

A

Ethanol, Isoniazid, Pyrazinamide, Cycloserine, Chloramphenicol, Copper chelation/deficiency, Zinc intoxication, Lead Intoxication

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2
Q

11-2. What laboratory features are associated with megaloblastic anemia (morphology and biochemistry)?

A

Morphology
Peripheral blood:
Pancytopenia, macrocytosis (increased MCV), oval macrocytes, hypersegmented neutrophils, variation in RBC shape

Bone marrow:
Erythroid hyperplasia, megaloblastic anemia, giant band neutrophils, giant metamyelocytes

Biochemistry
Peripheral blood:
Decreased B12 and/or folate 
Increased LD
Antiparietal cell antibodies
Antibody to intrinsic factor
Increased serum iron
Hypokalemia
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3
Q

11-3. What xenobiotics are associated with megaloblastic anemia (B12 deficiency and Folate deficiency)?

A 
B12 deficiency (8):
Paraminosalicylic acid
Cochicine
Neomycin
Ethanol
Omeprazole
Hemodialysis
Zidovudine
Fish tapeworm
Folate deficiency (9):
Phenytoin
Primidone
Carbamazepine
Phenobarbital
Sulfasalazine
Cholestyramine 
Triamterine
Malabsorption syndromes
Antimetabolites
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4
Q

11-4. What drugs and other chemicals are associated with the development of aplastic anemia (53)?

A 
Chloramphenicol
Methylphenylethylhydantoin
Gold
Penicillin
Methicillin
Sulfisoxazole
Mefoquine
Carbimazole
Propylthiouracil
Chlorpropamide
Indomethacin
Meprobramate
Mepazine
Thiocyanate
Bismuth
Carbon tetrachloride
Azidothymidine
Trifluoperazine
Organic arsenicals
Trimethadione
Streptomycin
Allopurinol
Sulfonamides
Sulfamethoxypryridazine
Ethosuximide
Methylmercaptoimidazole
Tolbutamide
Carbutamide
Carbamazepine
Chlorpromazine
Methazolamide
Mercury
Cimetidine
Ticlopidine
d=Penicillamine
Quinacrine
Phenylbutazone
Benzene
Tetracycline
Chlortetracycline
Amphotericin B
Felbamate
Potassium perchlorate
Pyrimethamine
Tripelennamine
Diclofenac
Chlordiazepoxide
Parathion
Dinitrophenol
Chlordane
Metolazone
Isoniazid
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5
Q

11-5. What xenobiotics are associated with methhemoglobinemia (therapeutic agents and environmental agents)?

A 
Therapeutic agents (17):
Benzocaine
Lidocaine
Prilocaine
Dapsone
Amyl nitrate
Isobutyl nitrite 
Nitroglycerine
Primaquine
Sulfonamide
Phenacetin
Nitric oxide
Phenazopyridine
Metoclopramide
Flutamide
Silver nitrate
Quinones
Methylene blue
Environmental agents (14):
Nitrites
Nitrates
Nitrobenezenes
Aniline dyes and aniline derivatives
Butyl nitrite
Potassium chlorate
Gasoline additives
Aminobenzenes
Nitrotoluenes
Trinitrotoluene
Nitroethane
ortho-Toluidine
para-Toluidine
b-Naphthol disulfonate
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6
Q

11-6. What xenobiotics are associated with oxidative injury (21)?

A 
Acetanilide
Napthalene
Nitrofuarantoin
Sulfamethoxypyridazine
Aminosalicylic acid
Sodium sulfoxone
Dapsone
Phenazyopyridine
Primaquine
Chlorates
Sulfasalazine
Phenylhydrazine
Nitrobenzene
Phenacetin
Phenol
Hydroxylamine
Methylene blue
Toluidine blue
Furazolidone
Nalidixic acid
Sulfanilamide
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7
Q

11-7. What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Uncommitted (totipotential stem cell)
CFU-S

A

Stage of development:
Uncommitted (totipotential) stem cell
CFU-S

Disease:
Aplastic anemia

Offending drugs:
Chloramphenicol
Gold salts
Phenylbutazone
Phentoin
Mephenytoin
Carbamazepine
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8
Q 
11-7.  What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Committed stem cell
CFU-G
CFU-E
BFU-E
A

Stage of development:
Committed stem cell

CFU-G

CFU-E
BFU-E

Disease and (offending drugs):
Aplastic anemia
(carbamazepine)

Agranulocytosis
(Chlorpromazine, carbamazepine, clozapine)

Pure red cell aplasia
(Phenytoin)

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9
Q

11-7. What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Morphologically recognizable precursors

A

Stage of development:
Morphologically recognizable precursors

Disease:
Hypoplastic marrow

Drugs:
Most cancer chemotherapy agents

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10
Q

11-7. What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Dividing pool:
Promyelocyte
Myelocyte

A

Stage of development:
Dividing pool:
Promyelocyte
Myelocyte

Disease:
Hypoplastic marrow

Drugs:
Chlorampenicol
Alcohol

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11
Q

11-7. What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Nondividing pool:
Metamyleocytes, bands
PMNs

A

Stage of development:
Nondividing pool:
Metamyleocytes, bands
PMNs

Disease:
Agranulocytosis

Drugs:
Clozapine
Phenothiazines

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12
Q

11-7. What are the stages of granulocytopoiesis with site of xenobiotic-induced cellular damage?
Peripheral blood lysis
Metamyleocytes, bands

A

Stage of development:
Peripheral blood lysis
Metamyleocytes, bands

Disease:
Agranulocytosis

Drugs:
Clozapine, etc
Aminopyrine

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13
Q

11-8. Examples of Toxicants that cause Immune and Nonimmune Idiopathic Neutropenia?
Drugs associated with WBC Antibodies

A 
Drugs associated with WBC Antibodies:
Aminopyrine
Propylthiouracil
Ampicillin
Metiamide
Dicloxacillin
Phenytoin
Aprindine
Azulfidine
Chlorpropamide
CPZ/phenothiazines
Procainamide
Nafcillin
Tolbutamide
Lidocaine
Methimazole
Levamisole
Gold
Quinidine
Clozapine
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14
Q

11-8. Examples of Toxicants that cause Immune and Nonimmune Idiopathic Neutropenia?
Drugs NOT associated with WBC Antibodies

A 
Drugs NOT associated with WBC Antibodies:
INH
Rifampicin
Ethambutol
Allopurinol
Phenothiazines/CPZ
Flurazepam
HCTZ
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15
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Hapten-directed antibody

A

Prototypic agent:
Penicillin

Antigen/epitope:
Drug

Platelet Effect:
Opsonization
Increased clearance

Clinical Effect:
Bleeding

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16
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Acquired antibody to drug-induced epitope

A

Prototypic agent:
Quinidine

Antigen/epitope:
Drug-GP Ib/IX/V
Drug-GP IIb/IIIa

Platelet Effect:
Opsonization
Increased clearance

Clinical Effect:
Bleeding

17
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Natural antibody to drug-induced epitope

A

Prototypic agent:
Abciximab

Antigen/epitope:
Drug-GP IIb/IIIa

Platelet Effect:
Opsonization
Increased clearance

Clinical Effect:
Bleeding

18
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Induction of autoimmune antibodies

A

Prototypic agent:
Gold

Antigen/epitope:
Platelet membrane

Platelet Effect:
Opsonization
Increased clearance

Clinical Effect:
Bleeding

19
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Immune complex

A

Prototypic agent:
Heparin

Antigen/epitope:
Pf4-heparin complex

Platelet Effect:
Platelet activation
Platelet aggregation
Increased clearance

Clinical Effect:
Thrombosis

20
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Thrombotic thrombocytopenic purpura (TTP)

A

Prototypic agent:
Ticlopidine

Antigen/epitope:
vWF-cleaving protease

Platelet Effect:
Platelet activation
Platelet aggregation
Increased clearance

Clinical Effect:
Microvascular thrombosis
Microangiopathic hemolytic anemia

21
Q

11-9. Mechanism of Immune-mediated thrombocytopenia:

Hemolytic-uremic syndrome

A

Prototypic agent:
Mitomycin

Antigen/epitope:
Unknown

Platelet Effect:
Platelet activation
Platelet aggregation
Increased clearance

Clinical Effect:
Microvascular thrombosis
Microangiopathic hemolytic anemia

22
Q

11-10. Conditions Associated with Abnormal Synthesis of Vitamin K-dependent coagulation factors

A 
Warfarin and analogs
Rodenticides (eg, brodifacoum)
Broad-spectrum antibiotics
N-Methyl-thiotetrazole cephalosporins
Intravenous alpha-tocopherol
Dietary deficiency
Cholestyramine resin
Malabsorption syndrome
23
Q

11-11. Relationship between Xenobiotics and the development of specific coagulation factor inhibitors:
Coagulation Factor:
Thrombin

A

Coagulation Factor:
Thrombin

Xenobiotic:
Topical bovine thrombin
Fibrin glue

24
Q

11-11. Relationship between Xenobiotics and the development of specific coagulation factor inhibitors:
Coagulation Factor:
Factor V

A

Coagulation Factor:
Factor V

Xenobiotic:
Streptomycin
Penicillin
Gentamicin
Cephalosporins
Topical bovine thrombin
25
Q

11-11. Relationship between Xenobiotics and the development of specific coagulation factor inhibitors:
Coagulation Factor:
Factor VIII

A

Coagulation Factor:
Factor VIII

Xenobiotic:
Penicillin
Ampicillin
Chloramphenicol
Phenytoin
Methyldopa
Nitrofurazone
Phenylbutazone
26
Q

11-11. Relationship between Xenobiotics and the development of specific coagulation factor inhibitors:
Coagulation Factor:
Factor XIII

A

Coagulation Factor:
Factor XIII

Xenobiotic:
Isoniazid
Procainamide
Penicillin
Phenytoin
Practolol
27
Q

11-11. Relationship between Xenobiotics and the development of specific coagulation factor inhibitors:
Coagulation Factor:
von Willebrand factor

A

Coagulation Factor:
vW Factor

Xenobiotic:
Ciprofloxacin
Hydroxyethyl starch
Valproic acid
Griseofulvin
Tetracycline
Pesticides
28
Q

11-12. Examples of Problem-driven tests used to characterize hematologic observations in preclinical toxicology

A 
Flow cytometry
Heinz body preparation
Cell associated antibody assays (erythrocyte, platelet, neutrophil)
Erythrocyte osmotic fragility test
Erythrokinetic/ferrokinetic analyses
Cytochemical/histochemical staining
Electron microscopy
In vitro hematopoietic clonogenic assays
Platelet aggregation
Plasma fibrinogen concentration
Clotting factor assays
Thrombin time
Bleeding time
29
Q

11-13. WHO Grading Criteria for Subacute and Acute Hematotoxicity:

Hematologic Parameters (Adults) at Grade 0

A

Hematologic Parameters (Adults) at Grade 0:

Hemoglobin g/dL (nmol/L): 11.0 (6.8)

Leukocytes (1000/ul): 4.0

Granulocytes (1000/ul): 2.0

Platelets (1000/ul): 100

Hemorrhage, blood loss: None

30
Q

11-13. WHO Grading Criteria for Subacute and Acute Hematotoxicity:

Hematologic Parameters (Adults) at Grade 1

A

Hematologic Parameters (Adults) at Grade 1:

Hemoglobin g/dL (nmol/L): 9.5 - 10.5 (6.5 - 6.7)

Leukocytes (1000/ul): 3.0 - 3.9

Granulocytes (1000/ul): 1.5 - 1.9

Platelets (1000/ul): 75-99

Hemorrhage, blood loss: Petechiae

31
Q

11-13. WHO Grading Criteria for Subacute and Acute Hematotoxicity:

Hematologic Parameters (Adults) at Grade 2

A

Hematologic Parameters (Adults) at Grade 2:

Hemoglobin g/dL (nmol/L): 8.0 - 9.4 (4.95 - 5.8)

Leukocytes (1000/ul): 2.0 - 2.9

Granulocytes (1000/ul): 1.0 - 1.4

Platelets (1000/ul): 50-74

Hemorrhage, blood loss: Mild

32
Q

11-13. WHO Grading Criteria for Subacute and Acute Hematotoxicity:

Hematologic Parameters (Adults) at Grade 3

A

Hematologic Parameters (Adults) at Grade 3:

Hemoglobin g/dL (nmol/L): 6.5 - 7.9 (4.0 - 4.9)

Leukocytes (1000/ul): 2.0 - 1.9

Granulocytes (1000/ul): 0.5 - 0.9

Platelets (1000/ul): 25-49

Hemorrhage, blood loss: Gross

33
Q

11-13. WHO Grading Criteria for Subacute and Acute Hematotoxicity:

Hematologic Parameters (Adults) at Grade 4

A

Hematologic Parameters (Adults) at Grade 4:

Hemoglobin g/dL (nmol/L): 6.5 (4.0)

Leukocytes (1000/ul): 1.0

Granulocytes (1000/ul): 0.5

Platelets (1000/ul): <25

Hemorrhage, blood loss: Debilitating

DABT (6 decks)

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