Flashcards in HemOnc--Pharmacology Deck (53):
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
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
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?
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?
ADP receptor inhibitors can cause..?
TTP or HUS
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
folic acid analog that inhibits DHF reductase-->decreases dTMP-->decreases DNA and protein synthesis
myelosuppression (reverse with folinic acid); macrovesicular fatty change in liver, mucositis, teratogen
pyrimide analog bioactivated to 5F-dUMP which covalently complexes folic acid to inhibit thymidylate synthase-->decrease dTMP-->decrease DNA and protein synthesis
myelosupression which cannot be reversed with folinic acid; overdose rescue with uridine; photosensitivty
pyrimidine analog-->inhibits DNA polymerase;
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?
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
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
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
neurotoxicity (areflexia, peripheral neuritis, paralytic ileus)
bone marrow supression
hyperstabilize polymerized mtubules in M phase so that mitotic spindle cannot break down; use in ovarian and breast carcinomas
myelosuppression, alopecia, hypersensitivity
cisplatin, carboplatin moa? use?
cross links DNA; testicular/bladder/ovary/lung carcinoma
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
melanoma, CML, sickle cell disease (increased HbF)
imatinib moa? tox?
tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI and stromal tumors); fluid retention