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PR3154 Haematology > Pharmacology for Blood Disorders > Flashcards

Pharmacology for Blood Disorders Flashcards

1
Q

What are the 4 types of Drug-induced blood dyscrasias that are the leading causes of death?

A
  1. Aplastic anemia
  2. Immune thrombocytopenia
  3. Agranulocytosis
  4. Hemolytic anemia
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2
Q

What drugs can cause aplastic anemia and how (mechanism of toxicity)?

A
  1. Dose-dependent (Direct): Cancer chemotherapy, chloramphenicol
  2. Idiosyncratic (Metabolites): Carbamazepine, phenytoin
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3
Q

How to manage aplastic anemia?

A
  1. Withdraw causative agent
  2. Immunosuppressant (CS, Ciclosporin, Cyclophosphamide, azathioprine, antithymocyte immunoglobulin)
  3. GM-CSF (Sargramostim)
  4. G-CSF (Filgrastim)
  5. IL-14
  6. RBC and platelet transfusion
  7. Infection treatment (Symptom)
  8. HSCT (May be necessary)
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4
Q

What drugs can cause immune thrombocytopenia?

A
  1. Heparin
  2. Sulphonamides
  3. Carbamazepine, phenytoin
  4. GP IIb/IIIa inhibitors (Abciximab, eptifibatide, tirofiban)
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5
Q

How to manage immune thrombocytopenia?

A
  1. Withdraw causative agent
  2. Immunosuppressants
  3. Platelet transfusion (for significant bleed)
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6
Q

What drugs can cause agranulocytosis / neutropenia and how (mechanism of toxicity)?

A
  1. Direct - Thiamazole, chlorpromazine, ticlopidine, busulfan, zidovudine
  2. Toxic metabolite - Clozapine, Carbimazole
  3. Immune (hapten / complement) mediated - Beta lactams, PTU
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7
Q

How to manage agranulocytosis?

A
  1. Withdraw causative agent
  2. Prophylaxis: G-CSF or GM-CSF
  3. Routine WBC monitoring weekly
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8
Q

What drugs can cause hemolytic anemia (immune and non-immune)?

A

Immune:
1. Autoantibody production
* Methyldopa (Drug-induced true)
* Quinine. quinidine (Innocent bystander immune complex)
2. Hapten-induced
* Penicillins, cephalosporins, streptomycin

Non-immune
* Protein adsorption - Cisplatin, oxaliplatin, BL inhibitors

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9
Q

How to manage hemolytic anemia?

A
  1. Withdraw causative agent
  2. RBC transfusion (for low hemoglobin)
  3. Hemodialysis (for acute renal failure)
  4. Steroids and immunoglobulins (serious)
  5. Rituximab Human anti-CD20 mab (for autoimmune hemolytic anemia)
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10
Q

What categories of drugs are used for anemia supportive therapy?

A

Nutrients
- Iron e.g., ferrous sulphate (PO), iron sucrose (Parenteral)
- Vitamin B12 e.g., hydroxocobalamin
- Folic Acid

ESAs
- Darbepoetin alfa, epoetin alfa

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11
Q

What drugs are used for neutropenia as supportive therapy?

A

Myeloid growth factors
- Recombinant G-CSF e.g., filgrastim, pegfilgrastim (+ plerixafor)
- Recombinant GM-CSF e.g., sargramostim

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12
Q

What drugs are used for thrombocytopenia as supportive therapy?

A

Megakaryocyte growth factors / Platelet-Stimulating Agents (PSAs)
- Recombinant IL-11 e.g., oprelvekin
- Fc-fusion protein thrombopoietin receptor agonist e.g., romiplostim
- Oral nonpeptide thrombopoietin receptor agonists e.g., eltrombopag

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13
Q

What are cytopenias?

A
  1. Anemia
  2. Neutropenia
  3. Thrombocytopenia
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14
Q

What drugs are used for blood cancers (leukemia, myelodysplastic syndrome, lymphoma)?

A
  • Corticosteroids
  • Immunosuppressants
  • Cytotoxic chemotherapeutic drugs
  • Targeted synthetic drugs
  • Biologics
  • Supportive therapies for cytopenias
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15
Q

How do nutrient deficits lead to anemia? What kind of erythrocytes are produced?

A

Vitamin B12 and folate deficiency:
- Inhibit DNA synthesis and cell multiplication
- Few large hemoglobin-rich erythrocytes

Iron deficiency:
- Inhibit hemoglobin synthesis
- Few small hemoglobin-poor erythrocytes

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16
Q

Iron ADRs? (Acute and Chronic)

How to treat overdose?

A
  • Acute GI: Necrotizing gastroenteritis with vomiting, abdominal pain, and bloody diarrhoea followed by shock, lethargy, dyspnea, metabolic acidosis, coma and death.
  • Chronic CV, liver: Haemochromatosis with iron deposited in heart, liver, pancreas and other organs → organ failure, death.
  • Parenteral deferoxamine or oral deferasirox iron chelators to treat overdose
17
Q

Which Vitamin B12 parenteral is preferred and why?

A

Hydroxocobalamin > Cyanocobalamin

More protein binding => Longer retention in circulation

18
Q

Why is oral vitamin B12 usually not effective?

A

Deficiencies usually due to GI malabsorption in the first place

19
Q

Vitamin B12 ADR

A
  1. Photosensitivity
  2. Injection site reaction
  3. HTN, hot flush, arrhythmias (secondary to hypokalemia)
  4. GI disturbance
  5. Dizziness, tremor, headache, paraesthesia
  6. Chromaturia, acneiform and bullous eruptions, rash and itching
20
Q

Vitamin B12 DDI

A

PPIs reduce oral absorption

21
Q

PK profile of folic acid

A
  1. Rapid absorption and peak (1h)
  2. 100% bioavailability
  3. Hepatic and plasma metabolism (Convert to 5MTHF) - Enterohepatic circulation
  4. Urine excretion
22
Q

When is folic acid contraindicated?

A

Untreated cobalamin deficiency (Include pernicious anemia untreated)

23
Q

What special precautions to take for folic acid?

A
  • Folate-dependent tumours, haemolytic anaemia, alcoholism.
  • Women with pre-existing diabetes, obesity, family history of neural tube defects, or previous pregnancy affected by neural tube defect.
  • Not appropriate for monotherapy in pernicious, aplastic, or normocytic anaemias when anaemia is present with vitamin B12 deficiency.
  • Children. Pregnancy and lactation.
24
Q

Folic acid ADR

A
  1. GI disorder, bitter taste, nausea, flatulence
  2. Immune disorder (Allergy, rare)
  3. Metabolism and nutrition disorder (Anorexia, rare)
25
Q

Folic acid DDI

A
  1. Anticonvulsant (Have reduced plasma conc)
  2. Lithium (Have enhanced efficacy)
  3. Methotrexate (Have reduced effect)
  4. Aspirin (Have increased elimination)
  5. Sulfasalazine, triamterene (Have reduced absorption)
  6. Chloramphenicol, cotrimoxazole (Interfere with folate metabolism)
26
Q

ESA Contraindications

A

Uncontrolled HTN

27
Q

ESA ADRs

A
  1. HTN, edema
  2. Thrombosis, platelet count increased, stroke
  3. Hyperkalemia
  4. Seizures
  5. Myalgia, arthralgia, limb pain
  6. GI effects (N/V)
  • Epoetin alfa: Pruritus
  • Darbepoetin alfa: Dyspnoea, cough, bronchitis
28
Q

G-CSF can be combined with…

A

Hematopoeitic stem cell mobilizer (Plerixafor)

29
Q

MOA of Myeloid growth factors

A
  • Stimulate myeloid progenitor cells

G-CSF
* Stimulates proliferation and differentiation of progenitors committed to neutrophil lineage and
* Additional activates phagocytic activity of mature neutrophils and prolongs their survival in circulation

GM-CSF broader spectrum effects than G-CSF
* Stimulates proliferation and differentiation of early and late granulocytic, erythroid and megakaryocyte progenitors

30
Q

Myeloid growth factors ADR

A
  1. Well tolerated: G-CSF > GM-CSF
  2. Bone pain (G-CSF) - Reversible
  3. Fever, malaise, arthralgia, myalgia (GM-CSF)
  4. Fatal:
    * Severe sickle cell crisis, capillary leak syndrome, respiratory failure or acute respiratory distress syndrome (ARDS)
    * Rarely, splenic rupture
31
Q

Special precautions for myeloid growth factors

A
  • Patient with pre-malignant or malignant myeloid condition, acute myeloid leukaemia; sickle-cell trait or disease, recent history of pneumonia or lung infiltrates, osteoporotic bone disease
  • Not indicated for use in chronic myeloid leukaemia or myelodysplastic syndrome
32
Q

Megakaryocyte growth factor ADRs

A
  1. Thromboembolism
  2. Fluid retention, peripheral edema, dyspnea on exertion (Oprelvekin)
33
Q

Special precaution of megakaryocyte growth factors

A
  • Patient with or with history of cerebrovascular disease
  • Risk factors for thromboembolism (e.g., advanced age, prolonged periods of immobilisation, malignancies, surgery/trauma, bleeding, obesity, smoking, contraceptives and hormone replacement therapy)
  • Eltrombopag: Higher dose required for patients of non-East Asian ancestry (e.g., not Chinese, Koreans, Japanese, Taiwanese, Thai)
  • Oprelvekin: Chronic heart failure or at risk of developing heart failure; and susceptibility to develop fluid retention

PR3154 Haematology (4 decks)

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