HemOnc--Pharmacology Flashcards
heparin moa?
cofactor for atIII, decreases thrombin and factor Xa
direct thrombin inhibitors
argatroban, bivalirudin–derivatives of hirudin
in HIT, what to use for anticoagulation?
argatroban or bivalirudin
warfarin moa?
interferes with synthesis and gamma-carboxlyation of vitamin K dependent clotting factors (2, 7, 9, 10 and proteins C and S)
how to follow warfarin effect?
extrinsic pathway–use PT/INR to monitor
warfarin tox?
bleeding, teratogenic (do not use in preg); skin/tissue necrosis esp if patient has genetic protein C/S deficiency; drug-drug interactions
Direct factor Xa inhibitors?
apixaban, rivaroxaban;
aspirin overdose? A/B derrangement
initially a respiratory alkalosis then superimposed by metabolic acidosis
ADP receptor inhibitors? moa?
clopidogrel, ticlopidine, prasugrel, ticagrelor; inhibits platelet aggregation by irreversibly blocking ADP receptors and prevents GPIIb/IIIa receptor expression, preventing fibrinogen binding
ADP receptor inhibitor that can cause neutropenia?
ticlopidine
ADP receptor inhibitors can cause..?
TTP or HUS
cilostazol, dipyradamole?
PDEIII inhibitors, increase cAMP in platelets–>inhibiting platelet aggregation; also vasodilates
GP IIb/IIIa inhibitors?
abciximab,eptifibatide, tirofiban; can cause thrombocytopenia
Cell cycle effect: vinca alkaloids and taxols
inhibit M phase
Cell cycle effect: antimetabolites
S phase; eg MTX, 5-FU, cytarabine, 6MP, 6TG, hdroxyurea
Cell cycle effect: etoposide
S and G2 phase
Cell cycle effect: bleomycin
G2 phase
methotrexate moa?
folic acid analog that inhibits DHF reductase–>decreases dTMP–>decreases DNA and protein synthesis
methotrexate tox?
myelosuppression (reverse with folinic acid); macrovesicular fatty change in liver, mucositis, teratogen
5-FU moa?
pyrimide analog bioactivated to 5F-dUMP which covalently complexes folic acid to inhibit thymidylate synthase–>decrease dTMP–>decrease DNA and protein synthesis
5FU tox?
myelosupression which cannot be reversed with folinic acid; overdose rescue with uridine; photosensitivty
cytarabine moa?
pyrimidine analog–>inhibits DNA polymerase;
cytarabine tox?
pancytopenia
azathioprine, 6MP, 6TG moa? tox?
purine (thiol) analogs–>decrease de novo purine synthesis; activated by HGPRT; tox to bone marrow/GI/liver
do not mix azathioprine or 6MP with…?
allopurinol (XO inhibitor)
dactinomycin moa? tox? use?
intercalates DNA; myelosuppresion; used in wilms tumor, ewing sarcoma, rhabomyosarcoma; childhood tumors
doxorubicin, daunorubicin moa? tox?
generate free radicals–>intercalate in DNA–>breaks DNA->decr replication; used in solid tumors, leukemias, lymphomas; cardiotoxic (dilated CM), myelosuppresion, alopecia
treat doxorubicin tox?
dexrazoxane (iron chelating agent) used to prevent cardiotoxicity
Bleomycin moa? tox?
induces free radical formation–>DNA strand breaks; pulmonary fibrosis, skin changes, mucositis; hyperpigmentation; use in testicular cancer/hodgkins
which antitumor antibiotic has minimal myelosuppresion?
bleomycin
what are some alkylating agents?
cyclophosphamide, ifosfamide, nitrosoureas, busulfan; all cross link DNA
cyclophosphamide, ifosfamide moa?
covalently x-link (interstrand) DNA at guanine N-7; requires bioactivation by liver
cyclophosphamide tox?
myelosuppresion; hemorrhagic cystitis that can be prevented with mesna (thiol group bind toxic metabolites)
nitrosuoureas moa? tox?
requires bioactivation and cross links DNA; CNS tox (convulsions/dizziness/ataxia)
what type of tumors is nitrosoureas specially used for?
CNS tumors including glioblastoma multiforme because it can penetrate BBB
busulfan is used for?
CML; and to ablate bone marrow before transplant
busulfan tox?
severe myelosuppression, pulmonary fibrosis, hyperpigmentation
what are some microtubule inhibitors?
vincristine, vinblastine, paclitaxols and other -taxols
vincristine, vinblastine moa? use?
vinca alkaloids that bind B-tubulin, inhibit polymerization and prevent mitotic spindle formation (M phase arrest); use in solid tumors/leukemia/lymphomas
vincristine tox?
neurotoxicity (areflexia, peripheral neuritis, paralytic ileus)
vinblastine tox?
bone marrow supression
paclitaxol moa?
hyperstabilize polymerized mtubules in M phase so that mitotic spindle cannot break down; use in ovarian and breast carcinomas
paclitaxel tox?
myelosuppression, alopecia, hypersensitivity
cisplatin, carboplatin moa? use?
cross links DNA; testicular/bladder/ovary/lung carcinoma
cisplatin/carboplatin tox?
nephrotoxic, acoustic nerve damage
prevent nephrotox of cisplatin?
amifostine (free radical scavenger) and chloride diuresis
etoposide, teniposide moa? tox?
inhibits topoisomerase II–>increase DNA degradation; myelosuppresion, GI irritation, alopecia
irinotecan, topotecan moa? tox?
topoisomerase I inhibition and prevents DNA unwinding and replication; severe myelosuppresion and diarrhea
hydroxyurea moa? tox?
inhibits ribonucleotide reductase–>decreases dna synthesis (S phase specific); bone marrow suppression, GI upset
hydroxyurea use?
melanoma, CML, sickle cell disease (increased HbF)
traztuzumab tox?
cardiotoxic
imatinib moa? tox?
tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI and stromal tumors); fluid retention
test before giving rituximab?
increased risk of PML, test for JC virus
