Pharmacology

Question 1

Differences among heparin, LMWH, and fondaparinux

Answer 1

LMWH and fondaparinux have better bioav, act on Xa, and have 2-4x longer half life, but not easily reversible

Question 2

Heparin mechanism

Answer 2

Activates antithrombin –> decreased thrombin (factor 2) and factor 10a

Question 3

Thrombin inhibitors

Answer 3

Argatroban, bivalirudin, dabigatran

Used instead of heparin for pts with HIT

Question 4

Warfarin mech + use

Answer 4

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)

Question 5

Warfarin AEs

Answer 5

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)

Question 6

Heparin reversal

Answer 6

Protamine sulfate (binds up heparin)

Question 7

Heparin-induced thrombocytopenia

Answer 7

IgG antibodies against platelet factor 4 develop –> heparin - PF4 - Ig complex –> activates plts –> thrombosis and subsequent thrombocytopenia

Question 8

Direct inhibitors of factor Xa

Answer 8

Apixaban, rivaroxaban

Question 9

Thrombolytics use

Answer 9

“-plas”

plasminogen –> plasmin to increase PT and PTT

Used for early MI, early ischemic stroke, direct thrombollysis of bad PE

Question 10

Reversal of thrombolytics toxicity

Answer 10

aminocaproic acid (inhibitor of fibrinolysis)

Question 11

Inhibitors of plt aggregation

Answer 11

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)

Question 12

Antineoplastics: nucleotide synth targets (drug, mech, dzs)

Answer 12

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

Question 13

Antineoplastics: DNA targets (drugs + mech)

Answer 13

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

Question 14

Antineoplastics: Cell division targets (drug + mech)

Answer 14

Vinca alkaloids (vinblastine, vincristine): inhibit MT formation

Paclitaxel: inhibits MT disassembly

Question 15

Alkylating agents

Answer 15

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)

Question 16

Microtubule inhibitors

Answer 16

1. Paclitaxel/taxols - stabilize polymerized MTs so mitotic spindle can’nt break down

used for ovarian and breast ca

2. Vinca alkaloids (Vincristine - NHL; Vinblastine - HL; both - solid tumors and leukemias) - inhibit MT polymerization so mitotic spindle can’t form

Question 17

Cisplatin, carboplatin

Answer 17

Cross-link DNA

Treat testicular, bladder, ovary, lung carcinomas

prevent nephrotox with amifostine (free radical scavenger) + diuresis

Question 18

DNA topo inhibitors

Answer 18

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

Question 19

Hydroxyurea

Answer 19

Inhibits ribonucleotide reductase –> decreased DNA synth

Treats melanoma, CML, sickle cell

Question 20

Bevacizumab

Answer 20

antibody against VEGF

treats solid tumors

Question 21

Erlotinib

Answer 21

EGFR tyrosine kinase inhib

treats NSCLC

may –> rash

Question 22

Imatinib

Answer 22

TK inhibitor of BCR-ABL (CML) and c-kit (GI stromal tumors)

may –> fluid retention

Question 23

Rituximab

Answer 23

antibody against CD20 (B cells)

treats non-Hodgkin lymphoma, CLL, IBD, RA

increased risk of PML

Question 24

Tamoxifen, raloxifene

Answer 24

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

Question 25

Trastuzumab

Answer 25

aka Herceptin

antibody against HER2 - kills HER2 positive breast and gastric cancer cells

may –> cardiotox

Question 26

Vemurafenib

Answer 26

BRAF inhibitor

treats melanoma