Hematology and oncology- Pharmacology Flashcards
Heparin-induced thrombocytopenia (HIT)
IgG antibodies against heparin bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets thrombosis and thrombocytopenia.
Heparin
- Adverse effects
- Antidote
Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions.
For rapid reversal (antidote), use protamine sulfate.
Direct thrombin inhibitors
- Names
- Clinical use
- Adverse effects and antidote
Bivalirudin, Argatroban, Dabigatran.
Venous thromboembolism, atrial fibrillation. Can be used in HIT.
Bleeding; can reverse dabigatran with idarucizumab. Consider PCC and/or antifibrinolytics (eg, tranexamic acid) if no reversal agent available.
Warfarin
- Adverse effects
Bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions. Initial risk of hypercoagulation: protein C
has a shorter half-life than factors II and X.
Cytochrome P-450 inhibitors increase warfarin effect.
Direct factor Xa inhibitors
- Names
- Clinical use
- Adverse effects
ApiXaban, rivaroXaban.
Treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial fibrillation
Bleeding. Not easily reversible.
Thrombolytics
- Names
- Clinical use
- Contraindications
- Antidote
Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA).
Early MI, early ischemic stroke, direct thrombolysis of severe PE.
Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension.
Nonspecific reversal with antifibrinolytics (eg, aminocaproic acid, tranexamic acid), platelet transfusions, and factor corrections (eg, cryoprecipitate, FFP, PCC).
ADP receptor inhibitors
- Names
- Clinical use
- Adverse effects
Clopidogrel, prasugrel, ticagrelor (reversible), ticlopidine
Acute coronary syndrome; coronary stenting
Neutropenia (ticlopidine). TTP may be seen.
Cilostazol, dipyridamole
- Mechanism
- Clinical use
- Adverse effects
Phosphodiesterase inhibitors; increase cAMP in platelets, resulting in inhibition of platelet aggregation;
vasodilators.
Intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin).
Nausea, headache, facial flushing, hypotension, abdominal pain.
Glycoprotein IIb/IIIa inhibitors
- Names
- Clinical use
- Adverse effects
Abciximab, eptifibatide, tirofiban
Unstable angina, percutaneous coronary intervention.
Bleeding, thrombocytopenia
Cancer drugs—cell cycle (imagen)
Pag. 426
Antimetabolites (mechanism and adverse effects)
- Azathioprine, 6-mercaptopurine
Purine (thiol) analogs, act in de novo purine synthesis.
Activated by HGPRT.
Myelosuppression; GI, liver toxicity.
Azathioprine and 6-MP are metabolized by xanthine
oxidase; thus both have toxicity with allopurinol or
febuxostat.
Antimetabolites (mechanism and adverse effects)
- Cladribine
Purine analog multiple mechanisms (eg, inhibition
of DNA polymerase, DNA strand breaks).
Myelosuppression, nephrotoxicity, and neurotoxicity.
Antimetabolites (mechanism and adverse effects)
- Cytarabine (arabinofuranosyl cytidine)
Pyrimidine analog DNA chain termination. At higher
concentrations, inhibits DNA polymerase.
Myelosuppression with megaloblastic anemia.
CYTarabine causes panCYTopenia.
Antimetabolites (mechanism and adverse effects)
- 5-fluorouracil
Pyrimidine analog bioactivated to 5-FdUMP, which
covalently complexes with thymidylate synthase and
folic acid. Capecitabine is a prodrug with similar activity.
Myelosuppression, palmarplantar erythrodysesthesia
(hand-foot syndrome).
Antimetabolites (mechanism and adverse effects)
- Methotrexate
Folic acid analog that competitively inhibits dihydrofolate reductase.
Myelosuppression, which is reversible with leucovorin. Hepatotoxicity.
Mucositis (eg, mouth ulcers).
Pulmonary fibrosis.
Folate deficiency, which may be teratogenic (neural tube defects) without supplementation.
Nephrotoxicity (rare).
Antitumor antibiotics (mechanism and adverse effects) - Bleomycin
Induces free radical formation breaks in DNA strands.
Pulmonary fibrosis, skin hyperpigmentation. Minimal
myelosuppression.
Antitumor antibiotics (mechanism and adverse effects) - Dactinomycin (actinomycin D)
Intercalates into DNA, preventing RNA synthesis.
Myelosuppression
Antitumor antibiotics (mechanism and adverse effects) - Doxorubicin, daunorubicin
Generate free radicals. Intercalate in DNA breaks in
DNA replication. Interferes with topoisomerase II enzyme.
Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.
Alkylating agents (mechanism and adverse effects) - Busulfan
Cross-links DNA.
Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.
Alkylating agents (mechanism and adverse effects) - Cyclophosphamide, ifosfamide
Cross-link DNA at guanine. Require bioactivation by liver. A nitrogen mustard
Myelosuppression; SIADH; hemorrhagic cystitis,
prevented with mesna (thiol group of mesna binds toxic
metabolites) or adequate hydration.
Alkylating agents (mechanism and adverse effects) - Nitrosoureas
Require bioactivation. Cross blood-brain barrier CNS. Cross-link DNA.
CNS toxicity (convulsions, dizziness, ataxia)
Alkylating agents (mechanism and adverse effects) - Procarbazine
Cell cycle phase–nonspecific alkylating agent, mechanism not yet defined.
Bone marrow suppression, pulmonary toxicity, leukemia
Microtubule inhibitors (mechanism and adverse effects) - Paclitaxel, other taxanes
Hyperstabilize polymerized microtubules in M phase so
that mitotic spindle canno break down.
Myelosuppression, neuropathy, hypersensitivity.
Microtubule inhibitors (mechanism and adverse effects) - Vincristine, vinblastine
bind β-tubulin and inhibit its polymerization into microtubules.
Vincristine: neurotoxicity, constipation.
Vinblastine: bone marrow suppression.
Cisplatin, carboplatin
- Mechanism
- Adverse effects
Cross-link DNA.
Nephrotoxicity, peripheral neuropathy, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis.
Etoposide, teniposide
- Mechanism
- Adverse effects
Inhibit topoisomerase II Increase DNA degradation
Myelosuppression, alopecia.
Irinotecan, topotecan
- Mechanism
- Adverse effects
Inhibit topoisomerase I and prevent DNA unwinding and replication.
Severe myelosuppression, diarrhea.
Hydroxyurea
- Mechanism
- Adverse effects
Inhibits ribonucleotide reductase decrease DNA Synthesis (S-phase specific).
Severe myelosuppression.
Bevacizumab
- Mechanism
- Adverse effects
Monoclonal antibody against VEGF. Inhibits angiogenesis.
Hemorrhage, blood clots, and impaired wound healing.
Erlotinib
- Mechanism
- Adverse effects
EGFR tyrosine kinase inhibitor.
Rash
Cetuximab
- Mechanism
- Adverse effects
Monoclonal antibody against EGFR
Rash, elevated LFTs, diarrhea.
Imatinib
- Mechanism
- Adverse effects
Tyrosine kinase inhibitor of BCR-ABL (Philadelphia chromosome fusion gene in CML) and c-kit (common in GI stromal tumors)
Fluid retention.
Rituximab
- Mechanism
- Adverse effects
Monoclonal antibody against CD20, which is found on most B-cell neoplasms.
risk of progressive multifocal leukoencephalopathy.
Bortezomib, carfilzomib
- Mechanism
- Adverse effects
Proteasome inhibitors, induce arrest at G2-M phase and apoptosis.
Peripheral neuropathy, herpes zoster reactivation.
Tamoxifen, raloxifene
- Mechanism
- Adverse effects
Selective estrogen receptor modulators (SERMs)—receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER ⊕ cells.
Tamoxifen—partial agonist in endometrium, which increase the risk of endometrial cancer; “hot flashes.”
Raloxifene—no increase in endometrial carcinoma (so you can relax!).
Both risk of thromboembolic events (eg, DVT, PE).
Trastuzumab (Herceptin)
- Mechanism
- Adverse effects
Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor.
Cardiotoxicity
Vemurafenib
- Mechanism
- Adverse effects
Small molecule inhibitor of BRAF oncogene ⊕ melanoma
Metastatic melanoma.
Rasburicase
- Mechanism
- Clinical use
Recombinant uricase that catalyzes metabolism of uric acid to allantoin.
Prevention and treatment of tumor lysis syndrome
Common chemotoxicities Cisplatin/Carboplatin Vincristine Bleomycin, Busulfan Doxorubicin Trastuzumab (Herceptin) Cisplatin/Carboplatin CYclophosphamide
ototoxicity peripheral neuropathy pulmonary fibrosis cardiotoxicity cardiotoxicity nephrotoxicity hemorrhagic cystitis
