ic4 - pharmacology for blood disorders Flashcards
what are the different drug induced blood dyscrasias
aplastic anemia, immune thrombocytopenia, agranulocytosis/ neutropenia, immune hemolytic anemia and non immune hemolytic anemia
what are the types and respective associating drugs for aplastic anemia
dose dependent direct drug toxicity -> cancer chemotx, chloramphenicol
idiosyncratic (by means of toxic metabolites) -> carbamazepine, phenytoin
how to manage aplastic anemia
- withdraw causative drug whenever possible
- use of immunosuppressants (glucocorticoids, ciclosporin, cyclophosphamide, azathioprine, antithymocyte immunoglobulin)
- transfusion of erythrocytes and platelets
- symptomatic tx for infections
- GM-CSF (sargramostim)
- G-CSF (filgrastim, peg filgrastim)
- IL14
- hematopoietic stem cell transplantation
what does GM CSF and GCSF stand for
granulocyte macrophage colony stimulating factor
granulocyte colony stimulating factor
what is aplastic anemia
when body stops producing enough new blood cells
what is immune thrombocytopenia
a type of platelet disorder
what are the drugs assoc with immune thrombocytopenia
heparin, sulfonamides, carbamazepine, phenytoin, glycoprotein IIb/IIIa inhibitor (eptifibatide)
how to manage immune thrombocytopenia
- withdraw causative drug whenever possible
- use of immunosuppressants
- platelet transfusions can be given if significant bleeding
what are the types and the drugs assoc with the different types of agranulocytosis/ neutropenia
direct drug toxicity -> thiamazole, chlorpromazine, ticlopidine, busulfan, zidovudine
toxic metabolite -> lozapine, carbamazepine
immune (hapten or complement mediated) -> beta lactam abx, propylthiouracil
how to manage agranulocytosis/ neutropenia
- withdraw causative drug whenever possible
- prophylactic administration of GM-CSF or G-CSF
- routine monitoring of wbc count esp for tx with clozapine
what is agranulocytosis/ neutropenia
low wbc count
what are the types of and the assoc drugs for the different types of immune hemolytic anemia
drug induced true Ab production -> methyldopa
innocent bystander (immune complex) autoAb production -> quinine, quinidine
hapten induced hemolysis -> penicillins, cephalosporins, streptomycin
what is immune hemolytic anemia
Ab forms and attacks own rbc
how to manage immune hemolytic anemia
- withdraw causative drug whenever possible
- RBC transfusion for pts with very low Hb
- HD may be required for acute renal failure
- steroids and immunoglobulins used if serious
- for autoimmune hemolytic anemia, use rituximab which is a human anti CD20 MAb
what are the types and the assoc drugs for the different types of non immune hemolytic anemia
protein adsorption -> cisplatin, oxaliplatin, beta lactamase inhibitor
how to manage non immune hemolytic anemia
- withdraw
- transfusion of rbc if low Hb
- HD if acute renal failure
- steroids and immunoglobulins if severe
- rituximab if autoimmune
what are the other types of drug induced blood dyscrasias
M2P3H2SCENL
methaemoglobinemia
megalobastic anemia
polycythemia
pure red cell aplasia
platelet dysfunction
hypoprothrombinemia
hypercoagulability
sideroblastic anemia
circulating anticoagulants
eosinophilia
neutropenia
acute leukemia
what are the respective assoc drugs and management strategy for each type of drug induced blood dyscrasias
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]
what is meant by the term cytopenia
cyto = cells
penia = deficits
what are the types of cytopenia and explain what each type of cytopenia are
anemia = deficit in RBC number or function
neutropenia = deficit in neutrophils
thrombocytopenia = deficit in platelets
what does vitB12 and folate deficiency cause
inhibition of DNA synthesis thus affecting cell multiplication leading to very few large Hb rich erythrocytes
what does iron deficiency cause
inhibition of Hb synthesis leading to a few small Hb poor erythrocytes
what kind of drugs are used for leukemia, myelodysplastic syndromes and lymphoma
corticosteroids, immunosuppressants, cytotoxic chemotx drugs, targeted synthetic drugs, biologics, supportive therapy for cytopenias
when supportive therapy is indicated for anemia, what to use
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
when supportive therapy is indicated for neutropenia, what to use
myeloid growth factors like G-CSF and GM-CSF (G-CSF include pegfilgrastim and filgrastim while GM-CSF includes sargramostim)
when supportive therapy is indicated for thrombocytopenia, what to use
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)
what are the different routes for Fe drugs for anemia
ferrous sulphate is PO, iron sucrose is IV
what is the elimination of Fe drugs for anemia
minimal in feces, bile, urine and sweat thus need careful dosing to avoid toxicity
what are the s/e for Fe drugs for anemia
acute: necrotising gastroenteritis with vomitting, abdominal pain and bloody diarrhea
chronic: hemochromatosis with Fe deposited in heart, liver, pancreas and other organs
what are the agents that can be used if overdosed with Fe
IV deferoxamine or PO deferasirox
what are the different formulations for vitB12 supplementation
hydroxocobalamin for IV cyanobalamin for PO
which formulation of vitB12 is preferred and why for supplementation
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
what are some PK features of vitB12 supplementation agents
excreted in urine and feces
elimination half life for IV is approx 30h
where is excess vitB12 from supplementation stored
in liver (about 3yrs supply)
what are the s/e of vitB12 supplementation agents
photosensitivity, injection site pain, hot flushing, HTN, arrhythmia secondary to hypoK, GI, dizziness, tremors, headache, acneiform and bollous, chromaturia, paresthesia, rash and itching
what are the ddi for vitB12 supplementation agents
PPI may decr absorption for PO
what are the PK features of folic acid supplementation
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
what is the c/i for folic acid supplementation
untreated vitB12 deficiency (incl. pernicious anemia), malignant diseases
what are the special population considerations for folic acid supplementation
- folate dependent tumors, hemolytic anemia, alcoholism
- women with preexisting DM, obesity, family hx of neural tube defects, previous pregnancy affected by neural tube defects
- not for monotx for pernicious, aplastic or normocytic anemia if vitB12 deficiency present
- children, pregnant, lactation
what are the ddi for folic acid supplementation
- ASM (PHT, PB, CBZ, VPA) can decr serum conc
- incr efficacy of Lithium
- incr elimination with aspirin
- decr efficacy of MTX
- sulfasalazine, triamterene decr absorption
- trimethoprim, sulfamethoxazole, chloramphenicol may intefere with folate metabolism
what are the s/e of folic acid supplementation
- GI (bitter taste, N, abdominal distensison, flatulence)
- immune (allergic rxn like rash, pruritus, erythema, urticaria, dypsnea, shock)
- metabolic and nutritional (anorexia)
what are the types of formulations for ESA for anemia
both parenteral
darboepoietin alfa
epoietin alfa
what is the moa of ESAs
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
what are the PK features of ESAs
absorption: IM slow, SQ slow and incomplete, IV rapid
distribution: liver, kidney, bone marrow
metabolism: limited
elimination: mainly in feces, small amounts in urine
what are the c/i for use of ESAs
uncontrolled HTN and hypersensitivity
what are the special populations to be considered when using ESAs
HTN, hx of seizure, ischemic vascular disease, sickle cell anemia, hepatic or renal impairment, pregnant, lactation, children
what are the s/e of using ESAs
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
what is the half life between epoietin alfa and darbepoietin alfa
epoietin alfa 4-13h while darbepoietin alfa 20-25h
darbepoietin alfa is conjugated with PEG and allows for q2w/ q1m dosing
what are the types of myeloid growth factors that can be used for neutropenia and which is used more freq and why
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
what might G-CSF be combined with
hematopoietic stem cell mobilisers called plerixafor
what is the moa of myeloid growth factors
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
what are the s/e (specifically for G-CSF and GM-CSF and other potentially fatal) for myeloid growth factors
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
what are the special populations to consider when using myeloid growth factors
acute myeloid leukemia, sickle cell trait/ disease, hx of pneumonia or lung infiltrate, osteoporotic bone disease
what are the c/i for myeloid growth factors
chronic myeloid leukemia or myelodysplastic syndrome
list the examples and types of megakaryocyte growth factors used for thrombocytopenia
oprelvekin is a recombinant IL11
romiplostim is a Fc fusion protein thrombopoietin receptor agonist
eltrombopag is a oral non peptide thrombopoietin receptor agonist
what is the general s/e profile of megakaryocyte growth factors
thromboembolic events
what are the s/e specific for use of oprelvekin
fluid retention, peripheral edema, dyspnea on exertion
what are the special precautions for use of megakaryocyte growth factors
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
what are the risk factors for thromboembolism
advanced age, malignancies, surgery/ trauma, bleeding, prolonged periods of immobilisation, smoking, obesity, contraceptives, hormone replacement tx
