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Flashcards in Heme drugs Deck (33):

herparin mech and clinical use

- cofactor for the activation of antithrombin
- decreases thrombin and factor Xa
- short half-life
- used for immediate anticoagulation for PE, ACS, MI and DVT
- used during pregnancy


heparin tox

- bleeding, HIT, osteoporosis, drug-drug interactions
- protamine is rapid reversal agent (+vely charged molecule that binds negatively charged heparin)



- development of IgG Abs to hep-PF4
- leads to thrombosis and thrombocytopenia


argatroban, bivalirudin

- derivatives of hirudin, the antcoagulant used by leeches, inhibit thrombin directly (binds thrombin active site)
- used instead of heparin for anticoagulating pts with HIT



- interferest with normal synthesis and gamma-carboxylation of vit K dependent clotting factors, protein C and S
- p450 metabolism
- has effect on extrinsic pathway (PT)
- tox: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions
- give FFP for faster reversal than Vit K


direct factor Xa inhibitors

- apixaban, rivaroxaban
- binds Xa directly and inhibits its activity
- used for treatment and prophylaxis for DVT and PE, stroke prophylaxis in pts with atrial fibrillation
- oral agents that do not require coag monitoring
- tox: bleeding, no specific reversal agent available


- alteplase (tPA), reteplase (rPA) and tenecteplase (TNK-tPA)

- directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots
- increases PT, PTT, no change in platelet count
- used in early MI, stroke, direct thrombolysis of severe PE
- tox: bleeding
- treat tox with aminocaproic acid



- irreversibly inhibits COX enzyme by covalent acetylation
- platelets cannot make new enzyme
- increased bleeding time, dec TXA and prostaglandins
- no effect on PT and PTT
- tox: GI ulceration, tinnitus, renal failure, interstitial nephritis, upper GI bleeding


ADP receptor inhibitors
- clopidogrel, ticlopidine, prasugrel, ticagrelor

- inhibit platelet aggregation by blocking ADP receptors
- inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
- used in ACS, coronary stenting, decreased incidence or recurrence of thrombotic stroke
- tox: neutropenia (ticlopidine), TTP/HUS may be seen
- can be substituted for aspirin in aspirin-induced asthma


cilostazol, dipyridamole

- PDE III inhibitors, inc cAMP in platelets, inhibiting aggregation, vasodilators
- used in claudication, coronary vasodilation, prevention of stroke, TIAs and angina ppx
- tox: nausea, headache, flushing, hypotension, abdominal pain


GP IIb/IIIa inhibitors
- abciximab, eptifibatide, tirofiban

- bind to GP IIb/IIIa receptors on activated platelets, preventing aggregation
- used for unstable angina, PCI
- tox: bleeding, thrombocytopenia



-folic acid analog that inhibits DHF reductase --> dTMP --> decreased DNA and protein synthesis
- used in leukemias, lymphomas and chronic sarcomas as well as abortion, ectopic preg, RA, psoriasis, IBD
- tox: myelosuppression (pancytopenia), macrovesicular fatty change in liver, mucositis, teratogenic
- can prevent myelosuppression with folinic acid rescue



- pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid
- this complex inhibits thymidylate synthase --> dec dTMP --> dec DNA and protein synthesis
- used in colon cancer, pancreatic cancer and basal cell carcinoma
- tox: myelosuppression (NOT reversible with leucovorin), photosensitivity, if overdose, "rescue" with uridine


cytarabine (arabinofuranosyl cytidine)

- pyrimidine analog --> inhibits DNA polymerase
- used in leukemias and lymphomas
- tox: leukopenia, thrombocytopenia, megaloblastic anemia
- CYTarabine causes panCYTopenia


azathioprine, 6-MP and 6-TG

- purine (thiol) analogs --> decreased de novo purine synthesis
- activated by HGPRT
- used in preventing organ rejection, RA and SLE, leukemia, IBD
- affects bone marrow, GI and liver
- azathioprine and 6-MP are metabolized by xanthine oxidase, so increased tox with allopurinol


Dactinomycin (actinomycin D)

- intercalates in DNA
- used for Wilms tumor, Ewing sarcoma, rhabdomyosarcoma
- used for childhood tumors - kids "act" out
- tox: myelosuppression


doxorubicin (adriamycin), daunorubicin

- generate free radicals
- intercalate in DNA --> breaks in DNA --> decreased replication
- used solid tumors, leukemias, lymphomas
- tox: cardiotoxicity, myelosuppression, alopecia
- dexrazone is used to prevent cardiotox



- induces free radical formation, which causes DNA breaks
- used in testicular cancer and Hodgkin lymphomas


cyclophosphamide, ifosfamide

- covalently X-link DNA at guanine N-7
- requires bioactivation in the liver
- used in solid tumors, leukemia, lymphomas and some brain cancers
- tox: myelosuppression, hemorrhagic cystitis (partially prevented with mesna)


nitrosoureas (carmustine, lomustine, semustine, streptozocin)

- requires bioactivation
- crosses BBB and cross links DNA
- used in brain tumors (GBM)
- tox: CNS tox -- convulsions, dizziness, ataxia



- cross-links DNA
- used in CML and used to ablate BM before transplant
- tox: severe myelosuppression, pulmonary fibrosis, hyperpigmentation


vincristine, vinblastine

- vinca alkaloids that bind B tubulin, inhibiting polymerization into microtubules, thereby preventing mitotic spindle formation ( M phase arrest)
- used in solid tumors, leukemias, lymphomas
- tox: vincristine - neurotox (areflexia, peripheral neuritis - tingling of hands/feet), paralytic ileus. vinblastine - BM suppression



hyperstabilize polymerized microtubules in M phase so the mitotic spindle cannot break down
- used in ovarian and breast carcinomas
- tox: myelosuppression, alopecia, hypersensitivity


cisplatin, carboplatin

- cross links DNA by forming ROS
- used in testicular, bladder, ovary and lung carcinomas
- tox: nephrotoxic and acoustic nerve damage
- prevent nephrotox with amifostine and Cl diuresis


etoposide, teniposide

- inhibits topoisomerase II --> inc DNA degradation
- used in solid tumors, leukemias and lymphomas
- tox: myelosuppression, GI irritation, alopecia


irinotecan, topotecan

- inhbits topoisomerase I and prevents DNA unwinding and replication
- irinotecan used in colon cancer, topotecan used in ovarian and small cell lung cancers
- tox: severe myelosuppression, diarrhea



- inhibits ribonucleotide reductase --> decreased DNA synthesis
- used in melanoma, CML, sickle cell disease
- tox: BM suppression, GI upset


trastuzumab (herceptin)

- anti Her 2 Ab
- used in breast and gastric cancer
- cardiotoixic
- "heart"ceptin hurts the heart


imatinib (gleevec)

- BCR-ABL and c-kit inhibitor
- used in CML and GIST
- tox: fluid retention



- monoclonal CD20 Ab
- used in non-hodgkin lymphoma, RA, ITP
- increased risk of PML



- small molecule inhibitor of forms of B-raf kinase within the V600E mutation
- used in metastatic melanoma



- monoclonal Ab against VEGF, inhibits angiogenesis
- used in solid tumors (colorectal, RCC)
- tox: hemorrhage and impaired wound healing


cladribine (2-CDA)

- an adenosine analog (inhibits adenosine deaminase)
- used in treatment of hairy cell leukemia