Hematology and Oncology Pharmacology

• Mechanism:
• -cofactor for activation of antithrombin
• -decreases thrombin and factor Xa
• -short half life

• Clinical Use:
• -PE
• -acute coronary syndrome
• -MI
• -DVT

• Toxicity:
• -bleeding
• -Heparin induced thrombocytopenia
• -osteoporosis
• -drug-drug interactions
• *antidote = protamine sulfate

• Notes:
• -LMWH: act more on factor Xa and have longer half life, not easily reversible
• -follow PTT

-development of IgG antibodies against heparin bound to platelet factor 4 (PF4)

-antibody-heparin-PF4 complex activates platelets → thrombosis and thrombocytopenia

• Mechanism:
• -derivatives of leech anticoagulant
• -inhibit thrombin

• Clinical Uses:
• -alternative to heparin for patients with HIT

• Mechanism:
• -interferes with synthesis and carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S)

• Clinical Use:
• -chronic anticoagulation
• -STEMI
• -venous thromboembolism prophylaxis
• -prevent of stroke in AFib

• Toxicity:
• -bleeding
• -teratogenic (CI in pregnancy)
• -skin/tissue necrosis
• -drug-drug interactions

• Notes:
• -reverse with vitamin K or fresh frozen plasma
• -follow PT

"The EX-PresidenT went to war(farin)"

• Ateplase (tPA)
• Reteplase (rPA)
• Tenecteplase (TNK-tPA)

• Mechanism:
• -aid conversion of plasminogen to plasmin (cleaves thrombin and fibrin clots)
• -increase PT and PTT, no change in platelet count

• Clinical Use:
• -early MI
• -early ischemic stroke
• -direct thrombolysis of severe PE

• Toxicity:
• -bleeding
• -CI: active bleeding, hx of intracranial bleeding, recent surgery, severe HTN
• -tx toxicity with aminocaproic acid

• Mechanism:
• -irreversibly binds COX (1 and 2)
• -platelets cannot synthesize new enzymes (effects last until new platelets are produced)
• -decrease TXA2 and PG formation
• -increase bleeding time, no effect on PT/PTT

• Clinical Uses:
• -antipyretic (intermediate dose)
• -analgesic (intermediate dose)
• -anti-inflammatory (high dose)
• -antiplatelet (low dose)

• Toxicity:
• -gastric ulceration
• -tinnitus
• -chronic use: renal failure, interstitial nephritis, GI bleeding
• -Reye's syndrome in children with viral infection
• -OD: metabolic acidosis and respiratory alkalosis

• Clopidogrel
• Ticlopidine
• Prasugrel
• Ticagrelor

• Mechanism:
• -inhibit platelet aggregation by irreversibly blocking ADP receptors
• -inhibit fibrinogen binding (block GpIIb/IIIa)

• Clinical Use:
• -acute coronary syndrome
• -coronary stenting
• -decrease incidence or recurrence of thrombotic stroke

• Toxicity:
• -neutropenia

• Mechanism:
• -Phosphodiesterase III inhibitor
• -increase cAMP in platelets (inhibiting aggregation)
• -vasodilators

• Clinical Uses:
• -intermittent claudication
• -coronary vasodilation
• -prevention of stroke or TIA (combined with ASA)
• -angina prophylaxis

• Toxicity:
• -Nausea
• -HA
• -facial flushing
• -hypotension
• -abdominal pain

• Abciximab
• Eptifibatide
• Tirofiban

• Mechanism:
• -bind GpIIb/IIIa and prevent platelet aggregation

• Clinical Use:
• -acute coronary syndrome
• -percutaneous transluminal coronary angioplasty

• Toxicity:
• -bleeding
• -thrombocytopenia

• Mechanism:
• -folic acid analog that inhibits DHFR
• -decrease DNA and protein synthesis

• Clinical Use:
• -leukemias
• -lymphomas
• -choriocarcinoma
• -sarcomas
• -abortion
• -ectopic pregnancy
• -RA-psoriasis

• Toxicity:
• -myelosuppression (leucovorin rescue)
• -macrovesicular fatty change in liver
• -mucositis
• -teratogenic

• Mechanism:
• -pyrimidine analog
• -inhibits DNA and protein synthesis

• Clinical Use:
• -colon cancer
• -basal cell carcinoma

• Toxicity:
• -myelosuppression (not reversible)
• -OD: rescue with thymidine
• -photosensitivity

• Mechanism:
• -pyrimidine analog
• -inhibition of DNA polymerase

• Clinical Use:
• -leukemias
• -lymphomas

• Toxicity:
• -Leukopenia
• -thrombocytopenia
• -megaloblastic anemia

• Mechanism:
• -purine analogs
• -decrease de novo purine synthesis
• -activated by HGPRT

• Clinical Use:
• -leukemias

• Toxicity:
• -BM
• -GI
• -Liver
• -increase toxicity with allopurinol

• Mechanism:
• -antitumor antibiotics
• -intercalates in DNA

• Clinical Use:
• -Wilm's tumor
• -Ewing's sarcoma
• -Rhabdomyosarcoma
• -childhood tumors
• "Children act out"

• Toxicity:
• -myelosuppression

• Mechanism:
• -antitumor antibiotics
• -generate free radicals
• -intercalate in DNA and generate breaks
• -reduces replication

• Clinical Use:
• -solid tumors
• -leukemias
• -lymphomas

• Toxicity:
• -cardiotoxicity (dilated cardiomyopathy)
• -myelosuppressive
• -alopecia
• -toxic to tissues following extravasation
• -dexrazoxane used to prevent cardiotoxicity

• Mechanism:
• -antitumor antibiotic
• -induces free radical formation causing breaks in DNA strands

• Clinical Use:
• -testicular cancer
• -Hodgkin's lymphoma

• Toxicity:
• -pulmonary fibrosis
• -skin changes
• -minimal myelosuppression

• Mechanism:
• -alkylating agent
• -cross linked into DNA
• -requires bioactivation by liver

• Clinical Use:
• -solid tumors
• -leukemias
• -lympomas
• -some brain cancers

• Toxicity:
• -myelosuppression
• -hemorrhagic cystitis
• -partially prevented with mensa

• Carmustine
• Lomustine
• Semustine
• Streptozocin

• Mechanism:
• -alkylating agents
• -require bioactivation
• -cross BBB

• Clinical Use:
• -brain tumors (glioblastoma multiforme)

• Toxicity:
• -CNS toxicity (dizziness, ataxia)

• Mechanism:
• -alkylates DNA

• Clinical Use:
• -CML
• -ablate marrow before HSCT

• Toxicity:
• -pulmonary fibrosis
• -hyperpigmentation

• Mechanism:
• -microtubule inhibitors
• -prevent mitotic spindle formation in M phase

"microtubules are the vines of your cells"

• Clinical Use:
• -solid tumors
• -leukemias
• -lymphomas

• Toxicity:
• -Vincristine: neurotoxic, paralytic ileus
• -Vinblastine: blasts BM

• "Vinblastine blasts bone marrow"

• Mechanism:
• -microtubule inhibitor
• -prevent mitotic spindle breakdown in M phase

"it's taxing to stay polymerized"

• Clinical Use:
• -ovarian carcinoma
• -breast carcinoma

• Toxicity:
• -myelosuppression
• -hypersensitivity

• Mechanism:
• -crosslink DNA

• Clinical Use:
• -testicular carcinoma
• -bladder carcinoma
• -ovary carcinoma
• -lung carcinoma

• Toxicity:
• -nephrotoxicity (prevent with amifostine and chloride diuresis)
• -acoustic nerve damage

• Mechanism:
• -inhibit topoisomerase II
• -increased DNA degradation

• Clinical Use:
• -solid tumors
• -leukemias
• -lymphomas

• Toxicity:
• -myelosuppression
• -GI irritation
• -alopecia

• Mechanism:
• -inhibits ribonucleotide reductase
• -decreases DNA Synthesis (S phase specific)

• Clinical Use:
• -Melanoma
• -CML
• -Sickle cell disease (increase HbF)

• Toxicity:
• -BM suppression
• -GI upset

• Mechanism:
• -may trigger apoptosis
• -may even work on non-dividing cells

• Clinical Use:
• -most commonly used GC in cancer chemotherapy
• -CLL
• -non-Hodgkin's lymphoma
• -immunosuppressant (autoimmune diseases)

• Toxicity:
• -Cushing like sx
• -immunosuppression
• -cataracts
• -acne
• -osteoporosis
• -HTN
• -Peptic ulcers
• -hyperglycemia
• -psychosis

• Mechanism:
• -SERMs
• -Estrogen R antagonists in breast
• -Estrogen R agonists in bone

• Clinical Use:
• -breast cancer treatment and prevention
• -prevent osteoporosis

• Toxicity:
• -T: partial agonist in endometrium (increased risk of endometrial cancer), hot flashes
• -R: no increased risk of endometrial cancer

• Mechanism:
• -anti-HER2
• -may cause antibody-dependent cytotoxicity of Her2+ cells

• Clinical Use:
• -HER2+ breast cancer

• Toxicity:
• -cardiotoxicity

• Mechanism:
• -philadelphia chromosome bcr-abl inhibitor

• Clinical Use:
• -CML
• -GI stromal tumors

• Toxicity:
• -fluid retention

• Mechanism:
• -anti-CD20

• Clinical Use:
• -Non-Hodgkin's lymphoma
• -RA (with methotrexate)

• Mechanism:
• -small molecule inhibitor of B-Raf with V600E mutation

• Clinical Use:
• -metastatic melanoma

• Mechanism:
• -anti-VEGF
• -inhibits angiogenesis

• Clinical Use:
• -solid tumors

• Cisplatin/Carboplatin
• -acoustic nerve damage
• -nephrotoxicity

• Vincristine
• -peripheral neuropathy

• Bleomycin, Busulfan
• -pulmonary fibrosis

• Doxorubicin
• -cardiotoxicity

• Trastuzumab
• -cardiotoxicity

• CYclophosphamide
• -hemorrhagic cystitis

• 5-FU
• -myelosuppression

• 6-MP
• -myelosuppression

• Methotrexate
• -myelosuppression