Pharmacology Flashcards
Differences among heparin, LMWH, and fondaparinux
LMWH and fondaparinux have better bioav, act on Xa, and have 2-4x longer half life, but not easily reversible
Heparin mechanism
Activates antithrombin –> decreased thrombin (factor 2) and factor 10a
Thrombin inhibitors
Argatroban, bivalirudin, dabigatran
Used instead of heparin for pts with HIT
Warfarin mech + use
Mech: inhibits gamma-carboxylation of vitamin K-dependent clotting factors 2, 7, 9, and 10 + proteins C and S (extrinsic pathway)
Use: chronic anticoag, c/i in preg (crosses placenta)
Warfarin AEs
Bleeding, skin/tissue necrosis, drug-drug interxns, transient hypercoag (Proteins C and S affected first, so do heparin bridging)
Reverse with vitamin K or FFP (faster)
Heparin reversal
Protamine sulfate (binds up heparin)
Heparin-induced thrombocytopenia
IgG antibodies against platelet factor 4 develop –> heparin - PF4 - Ig complex –> activates plts –> thrombosis and subsequent thrombocytopenia
Direct inhibitors of factor Xa
Apixaban, rivaroxaban
Thrombolytics use
“-plas”
plasminogen –> plasmin to increase PT and PTT
Used for early MI, early ischemic stroke, direct thrombollysis of bad PE
Reversal of thrombolytics toxicity
aminocaproic acid (inhibitor of fibrinolysis)
Inhibitors of plt aggregation
Aspirin (irrev inhibits COX)
ADP receptor inhib (“-grel” + ticlopidine; irrev blocks ADP rec so plts don’t put GPIIb/IIIa on surface and thus don’t cross link)
Cilostazol, dipyridamole (PDE III inhib –> increased cAMP in plts (and thus decreased agg) + vasodil)
GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
Antineoplastics: nucleotide synth targets (drug, mech, dzs)
MTX (ALL, lymphoma, choriocarcinoma, sarcoma, also ectopic preg, medical abortion, RA, psoriasis, IBD, vasculitis), 5-FU (CRC, panc ca, basal cell carcinoma): decrease thymidine synth
6-MP, azathioprine (metabolized to 6-MP), 6-thioguanine: decrease de novo purine synth, activated by HGPRT - used in chronic dz
Cladribine (2-CDA) = another purine analog - hairy cell leukemia
Cytarabine (arabinofuranosyl cytidine) = pyrimide analog, inhibits DNA pol - treat leukemias, lymphomas
Hydroxyurea: inhibit ribonucleotide reductase
Antineoplastics: DNA targets (drugs + mech)
Alkylating agents, cisplatin: cross-link DNA
Bleomycin: DNA strand breaks via free radical formation; treats testicular ca and Hodgkin lymphoma (may cause hyperpig, mucositis, minimal myelosupp (less than others))
Dactinomycin (childhood tumors - Wilsm, Ewing, rhabdomyosarcoma), doxorubicin (solid tumors, leukemias, lymphomas; can –> cardiotox [so give with dexrazoxane] and toxic to tissues if extravasate): DNA intercalators
Etoposide: inhibit topo II
Irinotecan: inhibit topo I
Antineoplastics: Cell division targets (drug + mech)
Vinca alkaloids (vinblastine, vincristine): inhibit MT formation
Paclitaxel: inhibits MT disassembly
Alkylating agents
All cross link DNA
Busulfan (CML, ablate bone marrow before transplant)
Cyclophosphamide, ifosfamide (act by liver; treat solid tumors, leuk, lymphomas) - toxic metabolites may –> hemorrhagic cystitis; prevent with mesna
Nitrosureas (cross BBB, use to treat brain tumors, but get CNS toxicity; no myelosupp as with others)
Microtubule inhibitors
- Paclitaxel/taxols - stabilize polymerized MTs so mitotic spindle can’nt break down
used for ovarian and breast ca
- Vinca alkaloids (Vincristine - NHL; Vinblastine - HL; both - solid tumors and leukemias) - inhibit MT polymerization so mitotic spindle can’t form
Cisplatin, carboplatin
Cross-link DNA
Treat testicular, bladder, ovary, lung carcinomas
prevent nephrotox with amifostine (free radical scavenger) + diuresis
DNA topo inhibitors
Topo I - irinotecan, topotecan (prevent DNA rep); used for CRC (irino), ovarian and SCLC (topo)
Topo II - etoposide, teniposide; used for solid tumors, leuk, lymphoma
Hydroxyurea
Inhibits ribonucleotide reductase –> decreased DNA synth
Treats melanoma, CML, sickle cell
Bevacizumab
antibody against VEGF
treats solid tumors
Erlotinib
EGFR tyrosine kinase inhib
treats NSCLC
may –> rash
Imatinib
TK inhibitor of BCR-ABL (CML) and c-kit (GI stromal tumors)
may –> fluid retention
Rituximab
antibody against CD20 (B cells)
treats non-Hodgkin lymphoma, CLL, IBD, RA
increased risk of PML
Tamoxifen, raloxifene
Selective estrogen receptor modulators (SERMS) - antag in breast, ag in bone
Tamox - breast ca treatment and prevention, but partial ag in endometrium so increased risk of endomet cancer
Ralox - osteopor prevention
