Flashcards in Heme & Onc Pharm Deck (160):
What is the MOA of heparin?
Cofactor for activation of antithrombin III
Decreases thrombin and factor Xa
What is the clinical use of heparin?
Immediate anticoagulant for PE, acute coronary syndrome, MI, DVT.
Can be used during pregnancy
What is the toxicity of heparin?
Bleeding, thrombocytopenia, osteoporosis, drug interactions.
What is the antidote for heparin toxicity?
What's the MOA of protamine sulfate?
I is a positively charged molecule that binds negatively charged heparin
What are the advantages to using low MW heparins?
Longer half life
More effect on factor Xa
Can be given subq
What is heparin induced thrombocytopenia?
Development of igG antibodies against heparin and platelet factor 4.
This complex of all 3 activates platelets causing thrombosis and thrombocytopenia
What is lepirudin, bivalirudin?
Anticoagulant used by leeches. Used as an alternative to heparin for patients with HIT
What is the MOA of lepirudin?
What is the MOA of warfarin?
Interferes with normal gamma carboxylation of vit-K dependent factors --> increased PT time
Metabolized by P450
What is the clinical use of warfarin?
Chronic anticoagulant after STEMI
venous TE prophylaxis
Chronic anticoagulant after a valve replacement or for anyone with a mechanical valve
What is the toxicity of warfarin?
What do you give to reverse the effects of warfarin?
Or fresh frozen plasma
What is the route of admin of heparin?
Where does heparin work?
In the blood
What is the duration of action of heparin?
What is the structure of heparin?
Large anionic, acidic polymer
What is the structure of warfarin?
Small lipid-soluble molecule
Where does warfarin act?
In the liver
What is the route of admin of warfarin?
What is the duration of action of warfarin?
What are the thrombolytics?
Alteplase (tPA), reteplase, tenecteplase
What is the MOA of thrombolytics?
Directly or indirectly convert plasminogen to plasmin --> cleaner thrombin and fibrin --> increased PT and PTT time
What are the clinical uses of thrombolytics?
Early MI, early ischemic stroke, direct thrombolysis of severe PE
What are the toxicities of thrombolytics?
What are the contraindications to thrombolytics?
Known bleeding diatheses
What is given to treat thrombolytics toxicity?
Aminocaproic acid - inhibitor of fibrinolysis
What is urokinase used for?
For tx of MI or PE
What is the MOA of urokinase?
Converts plasminogen to plasmin
What are the ADP receptor inhibitors?
Clopidrogrel, ticlodipine, prausgrel, ticagrelor
What is the MOA of clopidogrel?
Irreversibly blocking ADP receptors thereby inhibiting GPIIB/IIIa from binding fibrinogen
What are the clinical uses of clopidogrel?
Acute coronary syndrome, coronary scenting, decreased incidence or recurrence of thrombotic stroke.
What is the toxicity of ADP receptor inhibitors?
What is the MOA of cilostazol or dipyramidole?
Phosphodiesterase III inhibitor; increases camp in platelets to inhibit platelet aggregation
What is the clinical use of dipyramidole and cilostazol?
Intermittent claudication, coronary vasodilation, prevention of stroke or TIA, angina prophylaxis
What is the toxicity of cilostazol and dipyramidole?
What are the GPIIB/IIIa inhibitors?
What is the MOA of abciximab?
Binds to GPIIB/IIIa receptors on platelets and inhibits aggregation.
What is the clinical use of abciximab?
Acute coronary syndrome, percutaneous transluminal coronary angioplasty
What is the toxicity of abciximab?
What phase of the cell cycle do vinca alkaloids and taxols work in?
What cell cycle phase do etoposides work in?
G2, S phase
What cell cycle phase does bleomycin work in?
What cell cycle phase do anti metabolites work in?
What is the MOA of MTX?
Folic acid analog that inhibits dihydrofolate reductase so it decreases DNA and protein synthesis
What are the clinical uses of MTX?
Cancers, abortion, ectopic pregnancy, RA, psoriasis
What are the toxicities of MTX?
Macrovesicular fatty change in the liver
What is the rescue drug for MTX toxicity?
Leucovorin - used to reverse myelosuppression
What is the MOA of 5-fluorouracil?
Pyrimidine analog that's converted to 5F-dUMP which complexes with folic acid thereby inhibiting thymidylate synthase decreasing DNA and protein synthesis
What are the used of 5-fluorouracil?
What are the toxicities of 5-fluorouracil?
What can be used in an overdose of 5-fluorouracil?
What's th MOA of cytarabine?
Pyrimidine analog -- inhibitor of DNA synthesis
What is cytarabine used for?
What are the toxicities of cytarabine?
What is the MOA of azathioprine,6-mercaptopurine, 6-thioguanine?
Purine analogs -- inhibit de novo purine synthesis
Activated by HGPRT
Toxic to proliferating lymphocytes
What are the purine analogs used for?
Leukemia and kidney transplants
Autoimmune hemolytic anemia and glomerulonephritis
What are the toxicities of the purine analogs?
BM, GI, liver (cholestasis/hepatitis)
Increases with allopurinol because metabolized by xanthine oxidase
What is the MOA of dactinomycin?
Intercalates in DNA
What is dactinomycin used for?
Wilms tumor, Ewing's sarcoma, rhabdomyosarcoma,
What is the toxicity of dactinomycin?
What is the MOA of doxorubicin?
Generate free radicals
Intercalates in DNA noncovalentky causing breaks
What is doxorubicin used for?
Solid tumors, leukemias, lymphomas
What is the toxicity of doxorubicin?
What drug is used to prevent cardio toxicity of doxorubicin?
Dexrazoxane - iron cheating agent
What is the MOA of bleomycin?
Induces free radicals causing breaks in DNA
What are the clinical uses of bleomycin?
Hodgkin's lymphoma and testicular cancer
What are the toxicities of bleomycin?
Pulmonary fibrosis, skin changes, minimal myelosuppression
What are the alkylation agents?
What is the MOA of cyclophosphamide?
Covalently binds DNA at guanine N-7
Note: it is metabolized by P450
What is cyclophosphamide used for?
Solids tumors, leukemia, lymphoma, brain cancers
What is the toxicity of cyclophosphamide?
What substance can help prevent hemorrhagic cystitis caused by cyclophosphamide?
Mesna - binds toxic metabolite
What do alkylating agents require?
Which alkylating agent can cross the bb barrier?
Nitrosureas: carmustine, lomustine, semustine
What are nitrosureas used for?
What is the toxicity of nitrosureas?
What is the toxicity of busulfan?
What is busulfan used for?
Ablation of patients BM before transplant
What is the MOA of vincristine and vinblastine?
Binds to Tubulin in M phase and block polymerization of the micro tubules
What are alkaloids used for?
What is the toxicity of vincristine?
Neurotoxicity - areflexia, paralytic ileus, peripheral neuritis
What is the toxicity of vinblastine?
What is the MOA of taxols?
Hyper stabilize polymerized micro tubules in M Phase so they can't break down (anaphase cannot occur)
What are taxols used for?
Breast and ovarian carcinoma
What are the toxicities of taxols?
What is the MOA of cisplatin/carboplatin?
What is cisplatin/carboplatin used for?
Testicukar, bladder, ovary and lung cancer
What are the toxicities of cisplatin and carboplatin?
Acoustic nerve damage
How can nephrotoxicity of cisplatin be prevented?
Amifostine - free radical scavenger
What is the MOA of etoposide and teniposide?
Inhibit topoisomerase II - increases DNA degradation
What is the toxicity of etoposide?
What is the MOA of hydroxurea?
Inhibits ribonucleotide reductase decreasing DNA synthesis in S phase
What is hydroxurea used for?
What is the tox of hydroxurea?
How does prednisone work as a anti-neoplastic agent?
When is prednisone used in cancer?
What is the tox of prednisone?
What is the MOA of tamoxifen?
SERMs - receptor antagonists in breast and agonist in bone
Block binding if estrogen to ER positive cells
What is tamoxifen used for?
What is the tox of tamoxifen?
Partial agonist in endometrium so increases the risk of endometrial cancer
Which drug should be used for breast cancer in women who still have a uterus?
What is the MOA of trastuzamab (herceptin)?
Monoclonal Ab against Her-2 -- kills cells over expressing her-2
What is trastuzamab used for?
Her-2 positive breast cancer
What is the tox of trastuzamab?
What is the MOA of imatinib?
Philadelphia chromosome bCR-abl tyrosine kinase inhibitor
What is imatinib used for?
GI stromal tumors
What is the toxicity of imatinib?
What is the MOA of rituximab?
Monoclonal Ab against CD20
What is rituximab used for?
Non-Hodgkin lymphoma, RA
What is the MOA of vemurafenib?
Inhibits forms of the b-raf kinase with the V600E mutation
What is vemurafenib used for?
What is the MOA of bevaxizumab?
Monoclonal Ab against VEGF. Inhibits angiogenesis!
What is bevaxizumab used for?
What is the MOA of cyclosporine?
Binds to cyclophilins and this complex blocks the differentiation and activation of T cells by inhibiting calcineurin. Prevents production of IL-2 and its receptor
What is cyclosporine used for?
Suppresses organ rejection
What is the tox of cyclosporine?
What is the MOA of tacrolimus?
Binds FK-binding protein, inhibiting calcineurin and secretion of IL-2 and other cytokines
What is tacrolimus used for?
Suppression in organ transplant recipients
What is the tox of tacrolimus?
Same as cyclosporine but no gingival hyperplasia or hirsutism
What is the MOA of sirolimus (rapamycin)
Inhibits T cell prolif in response to IL-2
What is sirolimus used for?
Immunosuppression after kidney transplant in combo with cyclosporine and corticosteroids
What is the toxicity of sirolimus?
What is the MOA of muromonab?
Monoclonal Ab that binds to CD3 so T cells can't transduce
What is muromonab used for?
Immunosuppressive after kidney transplant
What is the toxicity of muromonab?
Cytokines release syndrome
What is aldesleukin?
What is aldesleukin used for?
Renal cell carcinoma
What is alpha interferon used for?
Hep B,C, kaposi's, leukemia, malignant melanoma
What is beta INF used for?
What is gamma INF used for?
Chronic granulomatous disease
What is oprelvekin?
Recombinant IL-11 used for thrombocytopenia
What is infliximab and adalimumab?
Monoclonal Ab to TNF-a
What are TNF-a monoclonal abs used for?
Crohn's, anklyosing spondylitis, RA, psoriatic arthritis
What is abciximab?
Monoclonal Ab to GPIIB/IIIa for prevention of cardiac ischemia in unstable angina
Percutaneous coronary intervention
What is omalizumab?
Monoclonal Ab to IgE used for asthma
What is celecoxib used for?
Inflammatory conditions such as RA without risk of GI bleed
What is COX2?
An inducible enzyme formed by inflammatory stimuli
Which platelet aggregation inhibitor causes neutropenia?
Ticlodipine - manifests as fever and mouth ulcers
What is a potential side effect of infliximab, adalimumab, and etanercept?
TB activation because of blocking TNF-alpha
What should be done before prescribing TNF-alpha?
Do a PPD test to check for inactive TB
What are the direct factor X inhibitors?
Ultra low MW heparin
What do direct factor X inhibitors prolong?
PT and PTT time
What do factor X inhibitors not inhibit and therefore not prolong?
Don't inhibit thrombin so don't prolong TT time
What are direct factor X inhibitors used for?
What is rat poison?
It is a long acting 4-hydroxycoumarin derivative - basically warfarin so it will deprive you of your vit K dependent factors
What should be given in the setting of rat poison?
Fresh frozen plasma
What does cryoprecipitate contain?
What is enoxaparin?
A low MW heparin
Greater activity against Factor Xa than thrombin
Why is unfractionated heparin preferred over other anticoagulants in acute coronary syndrome?
Because it complexes with both antithrombin and thrombin to allow antithrombin to inactivate Factor Xa thereby also inhibiting thrombin
What is given in subarachnoid hemorrhage and why?
Nimodipine due to risk of vasospasm from blood breakdown
DOC to treat vonWillenbrands disease?
What is the MOA of certolizumab?
It is a pegylated humanized monoclonal antibody that targets TNF-alpha. It lacks the Fc region and is used in treating autoimmune diseases
Uses for DDAVP?
What is the tx for primary myelofibrosis?
Ruxolitinib - JAK2 inhibitor
What is mercaptopurine inactivated by?
What is mercaptopurine activated by?
What is pentostatin?
An irreversible inhibitor of ADA
What is basiliximab?
Inhibitor of IL2 receptor