Heme/Onc Flashcards
Heparin
MOA: cofactor for the activation of antithrombin, decreased thrombin and decreased factor Xa
Clinical: immediate anticoagulant for PE, acute coronary syndrome, MI, DVT-prophylaxis in knee and hip surgery and non ambulatory patients
Used during pregnancy
Follow PTT
Toxicity: bleeding, thrombocytopenia (IgG antibodies againts heparin boud to platelet factor 4) , osteoporosis, drug-drug interactions
Protamine sulfate for antidote (postively charged binds negatively charged heparin-not effective for LMWH)
enoxaprin
LMWH
active antithrombiin III
Act more on factor Xa
Longer half life and better bioavailability
Administered subcutanoeusly and without lab monitoring
Significantly reduces death and recurrent MI when used acutely for MI
better for acute coronary syndrome
Argatroban, bivalirudin, lepirudin
Derivatives hirudin an anticoagulant used by leeches
Inhibit thrombin directly (do not require antithormbin III)
Used in patients with heparin induced thrombocytopenia
Warfarin
MOA: interfers with normal synthesis and y-carboxylation of glutamic acid of Vitamin K (clotting factors II, VII, IX and X, proteins C and S)
Metabolized by cytochrome P-450 pathway
Monitor PT/ INR
Clinical: chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in A. fib)
Not used in pregnant women
Toxicity: bleeding, teratogenic (fetal hemorrhagic jaundice, optic neuritis), skin/tissue necrosis, drug-drug interactions
Warfarin overdose: vitamin K antidote
Rapid reversal: fresh frozen plasma
Aixaban, rivaroxaban
MOA: direct Xa inhibitors
Clinical: treatment and prophylaxis of DVT and PE (Riva), stroke propylaxis in patients with A. fib
Toxicity: bleeding
Altepase, reteplase, tenectelplase
Thrombolytics-alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
MOA: diretly or indirectly aid conversion of plasminogen to plasmin which cleaves thrombin and fibrin cltos
Increases PT, PTT with no change in platelet count
Clinical: early MI (within 6 hours) early ischemic stroke, direct thrombolysis of severe PE, acute ST eleveation MI decreases mortality
Toxicity: Bleeding, restoration of blood flow after clot lysis can lead to benign arrhythmias
CI: patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
Treat toxicity with aminocarpoic acid inhibitor of fibrinolysis
Fresh frozen plasma and cryoprecipitate can also correct factor deficiencies
Aspirin
Irreversibly inhibits Cyclooxgenase (COX-1 and COX-2) by covalent acetlyation
Platelets cannot synthesize new enzyme
Increases BT, decreases TXA2, prostaglandins
No effect on PT or PTT
Clinical: Antipyretic, analgesic, anti-inflammatory, antiplatelet (decreases aggregation)
Toxicity: gastric ulceration, tinnitus,
Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding
Reye syndrome in children with viral infection
Overdose causes respiratory alkalosis then superimposed metabolic acidosis
Clopidogrel
ADP receptor inhibitors
MOA: inhibit platelet aggregation by irreversibly blocking ADP receptors
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
Clinical: Acute coronary syndrome, coronary stenting, decrease incidence or recurrence of thormbotic stroke
Toxicity: netuorpenia (ticlopidine-fever and mouth ulcers), TTP/HUS
Cilostazol
MOA: phsopdiesterase III inhibitor
Increase cAMP in platelets preventing platelet shape change and granule release
Inhibiting platelet aggregation
Vasodilates
Clinical: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (with aspirin), angina prophylaxis
Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain
Abcimiximab
GP IIb/IIIa inhibitors
MOA: bind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
Clinical: unstable angina, percutaneous transluminal coronary angioplasty
Toxicity: bleeding, thromobcytopenia
Radiation therapy
Initiates cell death by
1. DNA strand breakage
2. Formation of free radicals
Most pronounced in rapidly dividing cells
Side effects: damage to epithileal surfaces (bowel and skin)
Methotrexate
MOA: folic acid analog that inhibits dihydrofolate reductase (irreversible)
Decraeses dTMP leading to decreased DNA and decreased protein synthesis
S phase specific
Resultant Increase Dihydroflolate polyglutamate
Clinical: leukemias, lymphomas, choriocarcinoma, sarcomas
abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD, hydatiform mole
Toxicity: myelosuppresion-reversible with leucorvin
leucorvin does not require DHF reductase to convert to THF
Macorvesicular fatty change in liver (Incrased ALT and AST)
Mucositis, stomatitis-painful ulcers
Teratogenic
B cell lymphoma, opportunistic infections
Pulmonary fibrosis
5-fluorouracil
MOA: pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid
Inhibits thymidylate synthase leading to decreased dTMP and decreased DNA protein and protein synthesis
Clinical: colon cancer, pancreatic cancer, basal cell carcinoma
Toxicity: myelosuppression, photosensitivity
Overdose rescue with uridine
Cytarabine
MOA: pyrimidine analog leading to inhibition of DNA polymerase
Clinical: leukemias, lymphomas
Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia (panCYTOpenia)
Azathiprine, 6-mercaptopurine, 6-thioguanine
MOA: purine analogs decreasing de nova pruien synthesis
activated by HGPRT
Clinical: preventing organ rejection, Rheumatoid arthritis, SLE (Azothiroprine), leukemia and IBD (6-MP, 6-TG)
Toxicity: bone marrow, GI, liver
Axothioprine and 6-MP metabolized by xanthine oxidase which increases toxicity with allopurinol
Dactinomycin (actinomycin D)
MOA: intercalates in DNA
Clinical: wilms tumor, Ewing sarcoma, rhabdomyosarcoma
Childhood tumors
Toxicity: myelosuppression
Doxorubicin (Adriamycin), daunorubicin
MOA: generate free radicals
Intercalate in DNA leading to breaks in DNA decreasing replication
Clinical: solid tumors, leukemias, lymphomas
Toxicity: cardiotoxicity (dilated cardiomyopathy), myelosuppressin, alopecia
Toxic to tissues following extravasation
Dexrazoxane (iron chelator), prevents cardiotoxicity
Bleomycin
MOA: induces free radical formation which causes breaks in DNA strands
Clinical: testicular cancer, Hodgkin lymphoma
Toxicity: pulmonary fibrosis, skin changes, mucositis, minimal myelosuppression
Cyclophosphamide, ifosfamide
MOA: covalently X link DNA at guanine N-7
Require activation by liver
Clinical:solid tumors, leukemia, lymphomas, and some brain cancers
POLYARTERITIS NODOSA
WEGENERS, MICROSCOPIC POLYANGIITIS
Toxicity: myelosuppression, hemorrhagic cystitis,
Partially prevented with MESNA (bind acrolein)
Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
MOA: cross BBB
Cross link DNA
Clinical: brain tumors
Toxicity: convulsins, dizziness, ataxia
Busulfan
MOA: cross links DNA
Clinical: CML
Ablate bone marrow before transplantation
Toxicity: myelosuppression, pulmonary fibrosis, hyperpigmentation
Vincristine, vinblastine
MOA: bind B-tubulin inhibiting its polymerizatin into microtubles preventing mitotic spindle formation
M-phase arrest
Clinical: solid tumors, leukemias and lymphomas
Toxicity: Vincristine-neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Vinblastine-bone marrow suppression
Paclitaxel
MOA: Hyperstablize polymerized microtubules in M phase so mitotic spindle cannot break down (anaphase can’t occur)
Clinical: ovarian and breast carcinomas
Toxicity: myelosuppression, alopecia, hypersensitivity
Cisplatin, carboplatin
MOA: cross link DNA by forming ROS
Clinical: testicular, bladder, ovary and lung carciomas
Toxicity: nephrotxocity and acoustic nerve damage
Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis (Cisplatin is nonreactive when there is an increase in Cl concentration)
Etoposide
MOA: inhibits topoisomerase leading to increase in DNA degradation
Clinical: solid tumors (testicular and small cell lung cancer), leukemias, lymphomas
Genital warts-podophyllin
Toxicity: myelosuppression, GI irritation, alopecia
Irinotecan, topotecan
MOA: inhibit topisomerase I and prevent DNA unwinding and replication
Clinical: colon cancer (irinotecan), ovarian and small cell lung cancer (topotecan)
Toxicity: myelosuppression, diarrhea
Hydroxyurea
MOA: inhibits ribonucleotide reductase leading to decreased DNA synthesis (S phase specific)
Clinical: melanoma, CML, sickle cell disease (increases HbF)
Toxicity: bone marrow suppression, GI upset
Gardos blockers
Used in sickle cell
Calcium dependent K+ channel blockers
Gardos channels block transport of potassium and water through RBC membrane
Blocks efflux preventing dehydration of erythrocytes and polymerization of Hbs
Prednisone, prednisolone
MOA: may trigger apoptosis, may work on nondividing cells
Clinical: Most commonly used glucocorticoids in cancer chemotherapy
CLL, non-hodgkin lymphomas, immunosuppressant, autoimmune diseases
Toxicity: Cushing like smptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis (inhibits intestinal action of Vit. D), hypertension, peptic ulcers,hyperglycemia, psychosis
Tamoxifen, raloxifene
MOA: selective receptor modulators-receptor antagonists in breast and agonists in bone
block the binding of estrogen to ER
Clinical: breast cancer treatment (tamoxifen), and prevention, Ralaxoifeen useful in preventing osteoporosis
Toxicity: tamoxifen-partial agonist in endometrium, which increases the risk of endometrial cancer, hot flashes
Raloxifene-no increase risk of endometrial cancer
Agonist for cardiovascular system and blood lipoproteins
Trastuzumab
Herceptin
MOA: monocolonal Ab againts HER-2 a tyrosine kinase
Kills breast cancer cells that overexpres HER-2 through inhibition of HER2 initiated cellular signaling and Ab-dependent cytotoxicity
Clinical: HER2+ breast cancer and gastric cancer
Toxicity: cardiotoxicity
Imatinib
Gleevec
MOA: tyrosine kinase inhibitor of bcr-abl and c-Kit (GI stromal tumors)
Clinical: CML, GI stromal tumors
Toxicity: fluid retention
Rituximab
MOA: monoclonal Ab against CD20 which is found on B cell neoplasms
Clinical: non-hodgkin lymphoma, rheumatoid arthritis (with MTX), ITP
Toxicity: increase risk of progressive mutlifocal leukocencephalopathy
Verurafenib
MOA: small molecule inhibitor of forms of B-Raf kinase with V600E mutation
Clinical: metastatic melanoma
Bevacizumab
MOA: monoclonal Ab against VEGF inhibiting angiogenesis
Clinical: solid tumors (colorectal cancer, renal cell carcinoma)
Toxicity: hemorrhage, and impaired wound healing
dalteparin
LMWH
active antithrombiin III
Act more on factor Xa
Longer half life and better bioavailability
Administered subcutanoeusly and without lab monitoring
Significantly reduces death and recurrent MI when used acutely for MI
better for acute coronary syndrome
ticlopidine
ADP receptor inhibitors
MOA: inhibit platelet aggregation by irreversibly blocking ADP receptors
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
Clinical: Acute coronary syndrome, coronary stenting, decrease incidence or recurrence of thormbotic stroke
Toxicity: netuorpenia (ticlopidine-fever and mouth ulcers), TTP/HUS
prasugrel
ADP receptor inhibitors
MOA: inhibit platelet aggregation by irreversibly blocking ADP receptors
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
Clinical: Acute coronary syndrome, coronary stenting, decrease incidence or recurrence of thormbotic stroke
Toxicity: netuorpenia (ticlopidine-fever and mouth ulcers), TTP/HUS
ticagrelor
ADP receptor inhibitors
MOA: inhibit platelet aggregation by irreversibly blocking ADP receptors
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
Clinical: Acute coronary syndrome, coronary stenting, decrease incidence or recurrence of thormbotic stroke
Toxicity: netuorpenia (ticlopidine-fever and mouth ulcers), TTP/HUS
dipyridamole
MOA: phsopdiesterase III inhibitor
Increase cAMP in platelets preventing platelet shape change and granule release
Inhibiting platelet aggregation
Vasodilates
Clinical: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (with aspirin), angina prophylaxis
Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain
eptifibatide
GP IIb/IIIa inhibitors
MOA: bind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
Clinical: unstable angina, percutaneous transluminal coronary angioplasty
Toxicity: bleeding, thromobcytopenia
tiorfiban
GP IIb/IIIa inhibitors
MOA: bind to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
Clinical: unstable angina, percutaneous transluminal coronary angioplasty
Toxicity: bleeding, thromobcytopenia
teniposide,
MOA: inhibits topoisomerase leading to increase in DNA degradation
Clinical: solid tumors (testicular and small cell lung cancer), leukemias, lymphomas
Genital warts-podophyllin
Toxicity: myelosuppression, GI irritation, alopecia
podophyllin
MOA: inhibits topoisomerase leading to increase in DNA degradation
Clinical: solid tumors (testicular and small cell lung cancer), leukemias, lymphomas
Genital warts-podophyllin
Toxicity: myelosuppression, GI irritation, alopecia
Ristocetin
Activates vWF to bind to GpIb
Useful for diagnosis: normal platelet aggregation is not seen in von Willebrand disease
Desmopressin
Stimulates vWF release from endothelium
Used in vWF deficiency, diabetes insipidus and bed wetting
Cladribine
MOA: purine analog (adenosine) incorporated into DNA leading to DNA strand breaks
Clinical: hairy cell leukemia
Resistant to degradation by adenosine deaminase therefore able to reach high Intracellular concentrations
Fludarabine
MOA: purine analog
Used for CLL
Toxicity: Myelosuppression especially of CD4 and CD8 cells
Athralgias
Eculizumab
Prevents conversion of C5 to C5a decreasing the risk of thrombosis
Clinical: paroxysmal nocturnal hemoglobnuria
AE: increased risk of fatal meningococcal infections
High cost
Ruxolitinib
JAK2 inhibitor
Used for primary Myelofibrosis
Fondaparinux
Synthetic factor Xa inhibitor
Anticoagulant
Blood tranfusion therapy: packed RBCs and Platelets
RBCs: Increase Hb and O2 carrying capacity
Clinical: acute blood loss, severe anemia
Platelets: Increase platelet count
Clinical: stop significant bleeding (thrombocytopenia, qualitative platelet defects)
Fresh frozen plasma
Increase coagulation factor levels
Clinical: DIC, cirrhosis, warfarin overdose, exchange transfusion in TTP/HUS
Cryoprecipitate
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
Clinical: treat coagulation factor deficiencies involving fibrinogen and factor VIII
Blood transfusion risks
infection transmission (low)
transfusion reactions
iron overload (increased hemosiderin-yellow, brown pigment)
Hypocalcemia (citrate is calcium chelator)
Hyperkalemia (RBCs may lyse in old blood units)
Tranexamic acid
Antifibrinolytic agent for heavy menstruation, prevent excessive blood loss during certain surgeries.
