Hematology Pharm

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heparin

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- catalyzes activation of antithrombin III which decreases thrombin and Xa
- does not cross placenta
- used for immediate anticoagulation for pulm embolism, stroke, MI, DVT
- IV administered
- tox: heparin induced thrombocytopenia- heparin binds platelets causing autoAb production that destroys platelets and overactivates the remaining ones resulting in a thrombocytopenic, hypercoagulable state
-use protamine sulfate to reverse heparin effects
-new low MW heparins act more on Xa, longer 1/2 life

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lepirudin, bivalirudin

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-hirudin derivatives
- inhibit thrombin
-used as an alternative to heparin

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warfarin (coumadin)

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- inhibits epoxide reductase, thus interfering with the normal synthesis of vit K dependent clotting factors
-affects extrinsic pathway so ↑ PT on lab studies
- used for chronic anticoag, can cross placenta so no no for preggies
- tox: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions (eg: ketoconazole & erythromycin potentiates effects of warfarin b/c it inhibits P450)
- oral aministration

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thrombolytics- streptokinase, urokinase, tPA, APSAC (anistreplase)

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- aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots
- used for early MI, ischemic stroke
- ↑ PT and ↑ PTT
- tox: bleeding. treat tox with aminocaproic acid

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aspirin

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- acetylates and irreversibly inhibits COX 1 & COX 2 to prevent conversion of arachidonic acid to TxA2 which enhances platelet aggregation so no TxA2, no platelet aggregation
-increased bleeding time, no effect on PT, PTT
- used for: fever, pain, anti-inflammatory, antiplatelet action
- tox: gastric ulceration, bleeding, Reye's, tinnitus

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clopidogrel, ticlopidine

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- inhibit platelet aggregation by;
1. blocking ADP receptors
2. inhibit fibrinogen binding by preventing GP IIb/IIIa expression
- used for acute coronary syndrome,
- tox: neutropenia

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abciximab

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- monoclonal Ab that binds GP IIb/IIIa on activated platelets, preventing aggregation
- used for acute coronary syndromes, percutaneous transluminal coronary angioplasty
-tox: bleeding, thrombocytopenia

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Antineoplastics that fuck w/ nucleotide synthesis

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methotrexate- inhibit thymidine syntesis
5-FU- inhibit thymidine synthesis
- 6-mercaptopurine- inhibit purine synthesis

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antineoplastics that fuck w/ DNA

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alkylating agents- cisplatin (crosslinks DNA)
dactinomycin, doxorubicin- intercalate in DNA
etoposide- inhibits topoisomerase II

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antineoplastics that fuck with the cell itself

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vinca alkaloids- inhibit microtubule formation so fuck w/ mitosis

paclitaxel- inhibits microtubule disassembly

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methotrexate

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- s phase specific
- folic acid analog that inhibits dihydrofolate reductase resulting in decereased dTMP and decreased DNA synthesis
-used for leukemia, lymphoma, choriocarcinoma, sarcoma
tox- myelosuppression (reverse w/ leucovorin)

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5-flurouracil (5FU)

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-S phase specific
- pyrimidine analog bioactivated to 5F-dUMP which complexes with folic acid. this complex inhibits thymidylate synthase resulting in decreased dTMP
- used for colon cancer, basal cell carcinoma
- tox: myelosuppression

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6-mercaptopurine

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- blocks de novo purine synthesis
- activated by HGPRTase
-used for leukemias, lymphomas,
- tox: bone marrow, liver, GI.

***VERY IMPORTANT!!***
6-MU is metabolized by xanthine oxidase so DON'T give it with allopurinol cuz allopurinol inhibits xanthine oxidase and 6-MU won't be metabolized

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cytarabine

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- inhibits DNA polymerase
- used for AML, ALL. non hodgkin
- tox: leukopenia, thrombocytopenia, megaloblastic anemia

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cyclophosphamide, ifosfamide

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- alkylating agents. covalently x-link DNA
-requires bioactivation by liver
- used for non-Hodgkin, breast & ovarian carcinomas
- tox: myelosuppression, cystitis,

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nitrosureas- carmustine, loustine, semustine, streptozocin

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- alkylate DNA, require bioactivation
- cross blood brain barrier
- used for BRAIN TUMORS (glioblastoma)
-tox: CNS toxicity, ataxia, dizziness

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cisplatin, carboplatin

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- cross link DNA
-used for- testicular, ovarian, bladder, & lung cancers
- tox: nephrotoxicity, acoustic nerve damage (hearing impairment)

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busulfan

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- alkylates DNA
- used for CML, also used fro ablating bone marrow in stem cell transplants
- tox: pulm fibrosis, hyperpigmentation

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doxorubicin(adriamycin), dauorubicin

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- generate free radicals and intercalate DNA
-hodgkins, myeloma, solid tumors, sarcomas
- tox: CARDIOTOXICITY, myelosuppression, alopecia

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dactinomycin

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- intercalates DNA
- used for Wilm's tumor (nephroblastoma). ewing's sarcoma, rhabdomyosarcoma
-tox: myelosuppression

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bleomycin

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- induces formation of free radicals causing cuts in DNA
- used for ball cancer, hodgkin,
-tox: pulm fibrosis, skin changes

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hydroxyurea

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- inhibits ribonucleotide reductase, decrease DNA synthesis
-S phase specific
- used for melanoma, CML, sickle cell (increases HbF)
- tox: bone marrow suppression, GI

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etoposide

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- G2 phase specific
-inhibits topoisomerase II, increases DNA degradation
- used for small cell carcinoma of the lung, prostate cancer, ball cancer
- myelusuppression, GI, alopecia

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prednisone

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- glucocorticoid
-may trigger apoptosis
- used in CLL, hodgkin, immunosuppressant in autoimmune disorders (RA)
- tox: cushing like symptoms, immunosuppression, cataracts, acne, osteoporosis, HTN, ulcers, hyperglycemia, psychosis

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tamoxifen, raloxifene

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- block binding of estrogen to estrogen receptor + cells
- receptor antagonist in breast, agonist in bone
-used for breast cancer, may also prevent osteoporosis
- tox: may increase risk of endometrial carcinoma b/c of partial agonist effects (raloxifene don't do that)

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trastuzumab (herceptin)

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- monoclonal Ab against HER-2 receptors in metastatic breast cancer
-tox: cardiotoxicity

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imatinib (Gleevec)

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- philadelphia chromosome bcr-abl tyrosine kinase inhibitor
-used for CML, GI stromal tumors
- tox: fluid retention

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vincristine, vinblastine

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- M phase specific
- bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form
-used for Hodgkin, Wilm;s tumor, choriocarcinoma
- tox: bone marrow suppression (vinblastine), neurotoxicity (vincristine)

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paclitaxel (taxols)

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- M phase specific
- bind to tubulin and hyperstabilize polymerized microtubules so that mitotic spindle cannot break down
- anaphase cannot occur
- used for ovarian and breast cancers
- myelosuppression and hypersensitivity

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which antineoplastic drug can cause dilated cardiomyopathy

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doxorubicin, duanorubicin

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this anti cancer drug can cause hemorrhagic cystitis?

what should you give to prevent this complication?

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cyclophosphamide, ifosfamide can cause hemorrhagic nephritis

give MESNA

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this anti cancer drug can cause nephrotoxicity AND acoustic nerve damage

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cisplatin, carboplatin
(cross link DNA)

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these two anti-cancer drugs is associated w/ neurotoxicity

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nitrosureas (carmustine, lomustine, semustine, streptozocin)- alkylate DNA used for gliblastoma
- dizziness, ataxia

vincristine- block microtubule formation
-areflexia, peripheral neuritis

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cyclophosphamide & ifosfamide are 2 alkylating agents that can cause a particular complication that can be partially prevented with MESNA

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HEMORRHAGIC CYSTITIS