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pr3154 > ic4 - pharmacology for blood disorders > Flashcards

ic4 - pharmacology for blood disorders Flashcards

1
Q

what are the different drug induced blood dyscrasias

A

aplastic anemia, immune thrombocytopenia, agranulocytosis/ neutropenia, immune hemolytic anemia and non immune hemolytic anemia

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2
Q

what are the types and respective associating drugs for aplastic anemia

A

dose dependent direct drug toxicity -> cancer chemotx, chloramphenicol

idiosyncratic (by means of toxic metabolites) -> carbamazepine, phenytoin

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3
Q

how to manage aplastic anemia

A
  1. withdraw causative drug whenever possible
  2. use of immunosuppressants (glucocorticoids, ciclosporin, cyclophosphamide, azathioprine, antithymocyte immunoglobulin)
  3. transfusion of erythrocytes and platelets
  4. symptomatic tx for infections
  5. GM-CSF (sargramostim)
  6. G-CSF (filgrastim, peg filgrastim)
  7. IL14
  8. hematopoietic stem cell transplantation
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4
Q

what does GM CSF and GCSF stand for

A

granulocyte macrophage colony stimulating factor

granulocyte colony stimulating factor

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5
Q

what is aplastic anemia

A

when body stops producing enough new blood cells

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6
Q

what is immune thrombocytopenia

A

a type of platelet disorder

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7
Q

what are the drugs assoc with immune thrombocytopenia

A

heparin, sulfonamides, carbamazepine, phenytoin, glycoprotein IIb/IIIa inhibitor (eptifibatide)

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8
Q

how to manage immune thrombocytopenia

A
  1. withdraw causative drug whenever possible
  2. use of immunosuppressants
  3. platelet transfusions can be given if significant bleeding
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9
Q

what are the types and the drugs assoc with the different types of agranulocytosis/ neutropenia

A

direct drug toxicity -> thiamazole, chlorpromazine, ticlopidine, busulfan, zidovudine

toxic metabolite -> lozapine, carbamazepine

immune (hapten or complement mediated) -> beta lactam abx, propylthiouracil

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10
Q

how to manage agranulocytosis/ neutropenia

A
  1. withdraw causative drug whenever possible
  2. prophylactic administration of GM-CSF or G-CSF
  3. routine monitoring of wbc count esp for tx with clozapine
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11
Q

what is agranulocytosis/ neutropenia

A

low wbc count

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12
Q

what are the types of and the assoc drugs for the different types of immune hemolytic anemia

A

drug induced true Ab production -> methyldopa

innocent bystander (immune complex) autoAb production -> quinine, quinidine

hapten induced hemolysis -> penicillins, cephalosporins, streptomycin

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13
Q

what is immune hemolytic anemia

A

Ab forms and attacks own rbc

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14
Q

how to manage immune hemolytic anemia

A
  1. withdraw causative drug whenever possible
  2. RBC transfusion for pts with very low Hb
  3. HD may be required for acute renal failure
  4. steroids and immunoglobulins used if serious
  5. for autoimmune hemolytic anemia, use rituximab which is a human anti CD20 MAb
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15
Q

what are the types and the assoc drugs for the different types of non immune hemolytic anemia

A

protein adsorption -> cisplatin, oxaliplatin, beta lactamase inhibitor

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16
Q

how to manage non immune hemolytic anemia

A
  1. withdraw
  2. transfusion of rbc if low Hb
  3. HD if acute renal failure
  4. steroids and immunoglobulins if severe
  5. rituximab if autoimmune
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17
Q

what are the other types of drug induced blood dyscrasias

A

M2P3H2SCENL

methaemoglobinemia
megalobastic anemia
polycythemia
pure red cell aplasia
platelet dysfunction
hypoprothrombinemia
hypercoagulability
sideroblastic anemia
circulating anticoagulants
eosinophilia
neutropenia
acute leukemia

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18
Q

what are the respective assoc drugs and management strategy for each type of drug induced blood dyscrasias

A

methaemoglobinemia (phenazopyridine, dapsone, benzocaine, prilocaine) [withdraw, O2 and methylene blue]

megaloblastic anemia (PHT, PPI, MTX, azathiopurine, allopurinol, metformin, tetracycline) [withdraw, ensure adequate vitB12 and folic acid intake]

pure red cell aplasia (azathiopurine, CBZ, allopurinol, isoniazid) [withdraw, tx with immunosuppressants]

platelet dysfunction (beta lactam abx, aspirin, NSAIDs, fluoxetine) [withdraw, usually reversible]

polycythemia (erythropoietin, anabolic steroids) [withdraw, usually reversible]

hypercoagulability (COX2i, estrogen/ progestin, tamoxifen, erythropoietin) [withdraw, emergency tx of thrombosis]

hypoprothrombinemia (heparin, ticlopidine, aspirin, NSAIDs, tetracyclines, sulfonamides) [vigilant monitoring and dose adjust]

sideroblastic anemia (isoniazid, chloramphenicol, linezolid, penicillamine) [withdraw, treat with pyridoxine aka vitB6]

circulating anticoagulants (isoniazid, hydralazine, procainamide) [withdraw, give immunosuppressants]

eosinophilia (penicillin, sulfonamides, allopurinol, PHT) [withdraw, usually reversible]

neutropenia (glucocorticoids, epinephrin, co-trimoxazole) [withdraw, usually reversible]

acute leukemia (alkylating agents, topoisomerase II inhibitors, doxorubicin) [withdraw, treat leukemia]

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19
Q

what is meant by the term cytopenia

A

cyto = cells
penia = deficits

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20
Q

what are the types of cytopenia and explain what each type of cytopenia are

A

anemia = deficit in RBC number or function

neutropenia = deficit in neutrophils

thrombocytopenia = deficit in platelets

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21
Q

what does vitB12 and folate deficiency cause

A

inhibition of DNA synthesis thus affecting cell multiplication leading to very few large Hb rich erythrocytes

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22
Q

what does iron deficiency cause

A

inhibition of Hb synthesis leading to a few small Hb poor erythrocytes

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23
Q

what kind of drugs are used for leukemia, myelodysplastic syndromes and lymphoma

A

corticosteroids, immunosuppressants, cytotoxic chemotx drugs, targeted synthetic drugs, biologics, supportive therapy for cytopenias

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24
Q

when supportive therapy is indicated for anemia, what to use

A

nutrients like Fe, vitB12, folic acid (Fe in form of ferrous sulphate, iron sucrose and vitB12 is form of hydroxocobalamin)

erythropoiesis stimulating agents (ESAs) like darbepoetin alfa, epoetin alfa

25
Q

when supportive therapy is indicated for neutropenia, what to use

A

myeloid growth factors like G-CSF and GM-CSF (G-CSF include pegfilgrastim and filgrastim while GM-CSF includes sargramostim)

26
Q

when supportive therapy is indicated for thrombocytopenia, what to use

A

megakaryocyte growth factors/ platelet stimulating factors (PSAs) such as recombinant IL11, Fc fusion protein thrombopoietin receptor agonist, oral non peptide thrombopoietin receptor agonist (oprelvekin, romiplostim, eltrombopag respectively)

27
Q

what are the different routes for Fe drugs for anemia

A

ferrous sulphate is PO, iron sucrose is IV

28
Q

what is the elimination of Fe drugs for anemia

A

minimal in feces, bile, urine and sweat thus need careful dosing to avoid toxicity

29
Q

what are the s/e for Fe drugs for anemia

A

acute: necrotising gastroenteritis with vomitting, abdominal pain and bloody diarrhea

chronic: hemochromatosis with Fe deposited in heart, liver, pancreas and other organs

30
Q

what are the agents that can be used if overdosed with Fe

A

IV deferoxamine or PO deferasirox

31
Q

what are the different formulations for vitB12 supplementation

A

hydroxocobalamin for IV cyanobalamin for PO

32
Q

which formulation of vitB12 is preferred and why for supplementation

A

IV because it has higher protein binding and will thus be retained in circulation for longer

PO likely not effective as the vitB12 deficiency likely due to gastrointestinal malabsorption

33
Q

what are some PK features of vitB12 supplementation agents

A

excreted in urine and feces
elimination half life for IV is approx 30h

34
Q

where is excess vitB12 from supplementation stored

A

in liver (about 3yrs supply)

35
Q

what are the s/e of vitB12 supplementation agents

A

photosensitivity, injection site pain, hot flushing, HTN, arrhythmia secondary to hypoK, GI, dizziness, tremors, headache, acneiform and bollous, chromaturia, paresthesia, rash and itching

36
Q

what are the ddi for vitB12 supplementation agents

A

PPI may decr absorption for PO

37
Q

what are the PK features of folic acid supplementation

A

rapid absorption, F = 100% and peak effect in 1h

metabolised in the liver into 5-methylhydroxytetrafolate (5MHTF) metabolite that undergoes enterohepatic circulation

excreted in urine

38
Q

what is the c/i for folic acid supplementation

A

untreated vitB12 deficiency (incl. pernicious anemia), malignant diseases

39
Q

what are the special population considerations for folic acid supplementation

A
  1. folate dependent tumors, hemolytic anemia, alcoholism
  2. women with preexisting DM, obesity, family hx of neural tube defects, previous pregnancy affected by neural tube defects
  3. not for monotx for pernicious, aplastic or normocytic anemia if vitB12 deficiency present
  4. children, pregnant, lactation
40
Q

what are the ddi for folic acid supplementation

A
  1. ASM (PHT, PB, CBZ, VPA) can decr serum conc
  2. incr efficacy of Lithium
  3. incr elimination with aspirin
  4. decr efficacy of MTX
  5. sulfasalazine, triamterene decr absorption
  6. trimethoprim, sulfamethoxazole, chloramphenicol may intefere with folate metabolism
41
Q

what are the s/e of folic acid supplementation

A
  1. GI (bitter taste, N, abdominal distensison, flatulence)
  2. immune (allergic rxn like rash, pruritus, erythema, urticaria, dypsnea, shock)
  3. metabolic and nutritional (anorexia)
42
Q

what are the types of formulations for ESA for anemia

A

both parenteral
darboepoietin alfa
epoietin alfa

43
Q

what is the moa of ESAs

A

ESAs are biosynthetic forms of erythropoietin which stimulates division and differentiation of erythrocyte progenitor cells of RBC lineage

reticulocytes which are immature RBCs are released from bone marrow and mature into erythrocytes thus regulating erythropoiesis

44
Q

what are the PK features of ESAs

A

absorption: IM slow, SQ slow and incomplete, IV rapid

distribution: liver, kidney, bone marrow

metabolism: limited

elimination: mainly in feces, small amounts in urine

45
Q

what are the c/i for use of ESAs

A

uncontrolled HTN and hypersensitivity

46
Q

what are the special populations to be considered when using ESAs

A

HTN, hx of seizure, ischemic vascular disease, sickle cell anemia, hepatic or renal impairment, pregnant, lactation, children

47
Q

what are the s/e of using ESAs

A

HTN, edema, incr PLT count, thrombosis, stroke, seizure, myaljia, arthralgia, limb pain, GI (N/V)

pruritis for epoietin alfa
dyspnea, cough, bronchitis for darbepoietin alfa

48
Q

what is the half life between epoietin alfa and darbepoietin alfa

A

epoietin alfa 4-13h while darbepoietin alfa 20-25h

darbepoietin alfa is conjugated with PEG and allows for q2w/ q1m dosing

49
Q

what are the types of myeloid growth factors that can be used for neutropenia and which is used more freq and why

A

granulocyte colony stimulating factor (G-CSF) like pegfilgrastim and filgrastim

granulocyte-macrophage colony stimulating factor (GM-CSF) like sagramostim

G-CSF used more frequently as it is better tolerated

50
Q

what might G-CSF be combined with

A

hematopoietic stem cell mobilisers called plerixafor

51
Q

what is the moa of myeloid growth factors

A

general: to stimulate myeloid progenitor cells

G-CSF: stimulates proliferation and differentiation of progenitor cells of neutrophil lineage and additionally activates phagocytic activity of mature neutrophils to prolong their survival in circulation

GM-CSF: has broader spectrum effects by extending it to granulocytic, erythroid and megakaryocyte progeintors

52
Q

what are the s/e (specifically for G-CSF and GM-CSF and other potentially fatal) for myeloid growth factors

A

G-CSF: bone pain that is usually reversible when discontinued

GM-CSF: fever, myalgia, arthralgia, malaise

potentially fatal: ARDS/ respiratory failure, severe sickle cell crisis, capillary leak syndrome, rarely splenic rupture

53
Q

what are the special populations to consider when using myeloid growth factors

A

acute myeloid leukemia, sickle cell trait/ disease, hx of pneumonia or lung infiltrate, osteoporotic bone disease

54
Q

what are the c/i for myeloid growth factors

A

chronic myeloid leukemia or myelodysplastic syndrome

55
Q

list the examples and types of megakaryocyte growth factors used for thrombocytopenia

A

oprelvekin is a recombinant IL11

romiplostim is a Fc fusion protein thrombopoietin receptor agonist

eltrombopag is a oral non peptide thrombopoietin receptor agonist

56
Q

what is the general s/e profile of megakaryocyte growth factors

A

thromboembolic events

57
Q

what are the s/e specific for use of oprelvekin

A

fluid retention, peripheral edema, dyspnea on exertion

58
Q

what are the special precautions for use of megakaryocyte growth factors

A

general: patients with or hx of cerebrovascular disease, risk factors for thromboembolism, higher doses of eltrombopag if non-east asian ancestry

specific for oprelvekin: HF, susceptibility to develop fluid retention

59
Q

what are the risk factors for thromboembolism

A

advanced age, malignancies, surgery/ trauma, bleeding, prolonged periods of immobilisation, smoking, obesity, contraceptives, hormone replacement tx

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