heparin mechanism
activation of antithrombin III. major effect is decrease of factor 2a and 10a.
does heparin have a short or long half life
short
how to monitor heparin use
PTT
major complication with heparin
HIT or heparin induced thrombocytopenia.
rapid reversal of heparin
protamine sulfate- this is a positively charged molecule that binds negatively charged heparin.
enoxaparin and dalteparin
these are two low molecular weight heparins.
why is low moelcular weight heparin used
longer half life, better oral bioavilability. can be given subQ.
HIT
IgG antibodies against heparin bound to platelet factor 4. antibody and platelet complex activates the platelets so you get thrombosis and thrombocytopenia.
argatroban
hirudin derivative. anticoagulant used by leeches. inhibits thrombin directly. use with patients with HIT
bivalirudin
hirudin derivative. anticoagulant used by leeches. inhibits thrombin directly. use with patients with HIT
warfarin/coumadin
prevents gamma carboxylation of factors 2,7,9,10 C and S. metabolized by P450 system.
how to monitor warfarin dosing
PT
if skin tissue necrosis with warfain
think about protein C deficiency.
reversal of warfarin dose
vitamin K
rapid reversal of warfarin dose
fresh frozen plasma
apixaban and ribaroxaban
bind and inhibit xa. used for treatment and prohpylaxis of DVT and PE. also used as prophylaxis in patients with a fib.
one benefit of apixaban and ribaroxaban
oral agents
is warfarin oral
yes
which of heparin or warfain is teratogenic
warfarin
alteplase, reteplase and tenecteplase
these are all thrombolytics. they directly or indirectly convert plasminogen into plasmin. which cleaves thrombin and fibrin clots.
how to treat tpa or other thrombolytic overdose
aminocaproic acid. can also give fresh frozen plasma if needed.
how does aspirin increase bleeding time
mainly prevents TXA2 production from platelet which means no platelet aggregation.
aspirin overdose metabolic state
causes a respiratory alkalosis first and then metabolic acidosis. RK… MC.. gives a low Pco2 and low bicarbonate.
clopidogrel, ticlopidine, prasugrel and ticagrelor
ADP receptor blockers. prevent the Gp2b/3a from being produced. inhibits fibrinogen from making a clot. used mostly for coronary stenting.
clopidogrel, ticlopidine, prasugrel and ticagrelor side effects
neutropenia (ticlopidine). TTP and HUS may be seen
cilostazol and dipyridamole
phosphodiesterase III inhibitors. increase cAMP and therefore prevent platelets from aggregating. also cause vasodilation- used for claudication issues, prevention of stroke, angina etc
Abciximab, eptifibatide, tirofiban
bind to the glycoprotein Gp2b/3a and prevent aggregation. made from monoclonal antibody Fab fragments. used for angioplasty or unstable angina. can cause thrombocytopenia.
antimetabolites work in ____ cell cycle phase
S phase- DNA synthesis
Etoposide works in _____ cell cycle phase
G2 and S.
Bleomycin works in _____ cell cycle phase
G2
Vinca alkaloids and taxols work in ____ cell cycle phase
M phase
MTX mechanism
inhibits dihydrfolate rectase so decrease dTMP synthess. decreases both DNA replication and protein synthesis.
how to reverse myelosupression from MTX
leucovorin- folinic acid rescue
5FU mechanism
pyrimidine analog bioactivated to 5FdUMP. inhibits thymidylate synthase so decrease in dTMP and decrease DNA and protein synthesis. can cause photosensitivity
how to treat overdose of 5FU
uridine.
Cytarabine mechanism
pyrimidine analog so it inhibits DNA polymerase.
side effect of cytarabine
pancytopenia
aza mechanism
purine (thiol) analog. decreases de novo purine synthesis. activated by HGPRT
what drug can increase AZA toxicity
allopurinol. because Aza is broken down by xanthine oxidase
dactinomycin
intercalates DNA. used for childhood tumors. wilm tumor, ewing sarcoma etc.
doxorubicin - adriamycin and daunorubicin
generate free radicals and intercalate DNA. breaks in the DNA decrease its replication. used for solid tumors.
important toxicity with doxurubicin
cardiotoxicity - causes dilated cardiomyopathy
how to prevent cardiac toxicity with doxurubicin
dexrazoxane. iron chelating agent
bleomycin mechanism
induces free radicals which causes breaks in DNA strands. used for testicular cancer and Hodgkin Lymphoma
major side effect of bleomycin
pulmonary fibrosis. note- really minimal myelosupression
alkylating agent
adds an alkyl group to the guanine in the DNA at the 7th N in the purine ring.
cyclophosphamide and ifosfamide
covalently link an alkyl group to DNA at guanine N-7. requires bioactivation by the liver.
major side effect of cyclophosphamide and ifosfamide
hemorrhagic cystitis prevented with mesna- binds to the toxic metabolite
carmustine, lomustine, seustine, streptozocin
these are all nitrosourease= alkylating agents. require bioactivation. can cross the blood brain barrier. used for brain tumors! can cause cause CNS toxicity like ataxia
busulfan
cross links dna. it is an alkylating agent. used only in CML and to white out bone marrow before transplant.
side effects of busulfan
severe myelosupression, pulmonary fibrosis, hyperpigmentation
vincristine and vinblastine
these are vinca alkaloids that bind to beta tubulin and inhibit its polyermization- can’t form microtubules. this means no mitotic spindle formation in the cell- M phase arrest. used for solid tumors, leukemia and lymphoma.
vincristine toxicity
neurotoxicity - areflexia, peripheral neuritis, paralytic ileus
vinblastine toxicity
myelosupression- blasts away the marrow
paclitaxel and other taxols
hyeprstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down- no anaphase. used to treat ovarian and breast cancer.
cisplatin and carboplatin
cross link DNA. used for testicular, blader, ovary and lung cancer.
cisplatin and carboplatin toxicity
nephrotoxicity and acoustic nerve damage.
how to prevent nephrotoxicity from cisplatin and carboplatin
amifostine- free radical scavenger and chloride diuresis
etoposide, teniposide
topoisomerase II inhibitor- leads to DNA degradation. works for like testicular cancer and small cell lung cancer
irinotecan and topotecan
inhibit topoisomerase I. prevents DNA unwinding and replication. used in colon cancer (I) and ovarian and small cell lung cancer (T)
hydroxyurea
inhibits ribonucleotide reductase- decreases DNA synthesis. S phase specific. used in CML, melanoma and sickle cell disease (increases fetal hemoglobin)
Tamoxifen and raloxifene
selective estrogen receptor modulators- antagonist in breast and agonist in the bone. block the binding of estrogen to the ER in cells. use T for breast cancer and R for treatment of osteoporosis. T is an agonist in endometrium so you can get endometrial cancer. R is an endometrial antagonist so no increase in endometrial cancer.
Trastuzumab
this is herceptin. it is a monoclonal antibody against Her2 which is a tyrosine kinase receptor. used for two things- Her2 positive breast cancer and gastric cancer.
major toxicity of traztuzumab
cardiac-
Imatinib
this is gleevac. tyrosine kinase inhibitor of bcr-abl and cKit. used for CML and GI stromal tumors.
toxicity from Imatinib
fluid retention.
Rituximab
anti B cell- against CD20 which is found in most B cell cancers. increased risk of PML
Vemurafenib
inhibits the B raf kinase with the V600 E mutation. used only for metastatic melanoma.
bevacizumab
this is a monoclonal antibody against VEGF. inhibits angiogenesis. used for solid tumors like colon cancer and renal cell carcinoma. may cause hemorrhage and impaired wound healing
cisplatin/carboplatin toxicity
nephrotoxic and ototoxic- acoustic nerve damage
vincristine
this one causes the nerve issues- peripheral neuropathy and other neurologic issues
doxurubicin toxicity
cardiac
trastuzumab toxicity
cardiac
bleomycin and busulfan toxicity
both cause pulmonary fibrosis
cyclophosphamide toxicity
hemorraghic cystitis
5FU, 6MP and MTX toxicity
myelosupression