Heparin (mechanism)
Activates antithrombin III --> decreases activity of thrombin (IIa) and factor Xa --> blood as site of action Monitor PTT (intrinsic)
Heparin (antidote)
Protamine (chemical inactivation)
Heparin (use/placenta crossing)
Immediate anticoagulation for DVT, PE, MI
Can use during pregnancy (doesn’t cross placenta)
Heparin (side effects)
Skin necrosis at injection site
HIT
Bleeding (duh)
Warfarin (mechanism)
Inhibits gamma carboxylation of vit K-dependent factors (II, VII, IX, X, C, S) –> liver as site of action
Monitor PT/INR (extrinsic)
Warfarin (use/placenta crossing)
Chronic anticoagulation
Crosses placenta so don’t use in pregnant women
Warfarin (side effects)
Skin/tissue necrosis (usually seen first week of therapy -> due to protein C depletion b/c of its short HL -> so predisposition to this side effect w/ existing protein C and S deficiency)
Bleeding (duh)
Warfarin (antidotes)
Vit K
If severe, fresh frozen plasma
“-parin” (mechanism)
Enoxaparin, Dalteparin
LMW heparin: acts more on factor Xa (than II), longer HL, more bioavailable
Doesn’t need to monitor labs like normal heparin
“-parin” (side effect)
No antidote like heparin
“-xaban” (mechanism)
Apixaban, rivaroxaban
Direct factor Xa inhibitor
“-xaban” (3 uses)
Tx/prophylaxis of DVT, PE, stroke
“-xaban” (side effect)
No antidote like heparin or warfarin
“-teplase” (mechanism)
Thrombolytics (fibrin-specific so only attaches to recently formed clot) -> aid conversion of plasminogen to plasmin –> plasmin cleaves thrombin and fibrin clots (so prolong both PT and PTT)
Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
“-teplase” (3 uses)
Early MI
Early ischemic stroke (3-hr window)
Direct thrombolysis of severe PE
“-teplase” (side effects)
Verify that bleeding is not present before use!
Don’t use in severe HTN
Accelerated idioventricular rhythm (AIVR) -> reperfusion arrhythmia that is benign and self-resolving
“-teplase” (3 antidotes)
Aminocaproic acid (inhibits fibrinolysis)
Fresh frozen plasma
Cryoprecipitate
Aspirin (mechanism)
Inhibits both COX-1 and 2 by covalent acetylation –> antiplatelet AGGREGATION is from the effects on COX-1 (COX-2 is not present on platelets but on endothelium)
Aspirin (side effects)
Gastric ulcers, tinnitus (VIII), renal failure w/ chronic use
Reye syndrome in children with viral infection
Overdose: resp alkalosis superimposed by metabolic acidosis
“-grel” (mechanism)
Clopidogrel, prasugrel
Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
Prodrug that needs to be activated by P450
“-grel” (3 uses)
Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke
“-grel” (2 side effects)
TTP/HUS
Ticlopidine (mechanism)
Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
Ticlopidine (3 uses and 3 side effects)
Only when can’t tolerate aspirin or clopidogrel (1st line) -> for acute coronary syndrome, coronary stenting, reduces thrombotic stroke
Side effects: neutropenia (presenting as FEVER AND MOUTH ULCERS -> so monitor CBC biweekly for the first 3 months), TTP/HUS
Ticagrelor (mechanism)
Irreversibly blocking ADP receptor –> inhibits platelet AGGREGATION
Prevents GP IIb/IIIa from binding to fibrinogen
Ticagrelor (3 uses)
Acute coronary syndrome
Coronary stenting
Reduces thrombotic stroke
Ticagrelor (2 side effects)
TTP/HUS
Cilostazol (mechanism)
Phosphodiesterase III inhibitor –> increases cAMP inplatelets –> inhibits platelet aggregation
ALSO A DIRECT ARTERIAL VASODILATOR
Cilostazol (4 uses)
Intermittent claudication -> better than aspirin at peripheral arterial disease
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis
Cilostazol (5 side effects)
Flushing, abd pain, hypotension, nausea, headache
Dipyridamole (mechanism)
Phosphodiesterase III inhibitor –> increases cAMP inplatelets –> inhibits platelet aggregation
Vasodilator
Dipyridamole (4 uses)
Intermittent claudication
Coronary vasodilation
Prevention of stroke/TIAs (combined w/ aspirin)
Angina prophylaxis
Dipyridamole (5 side effects)
Flushing, abd pain, hypotension, nausea, headache
Abciximab (mechanism)
Monoclonal Ab Fab fragments, analog of fibrinogen
GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation
Abciximab (2 uses)
Unstable angina
Percutaneous transluminal coronary angioplasty
Abciximab (2 side effects)
Thrombocytopenia, bleeding
Eptifibatide (mechanism)
Analog of fibrinogen
GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation
Eptifibatide (2 uses)
Unstable angina
Percutaneous transluminal coronary angioplasty
Eptifibatide (2 side effects)
Thrombocytopenia, bleeding
Tirofiban (mechanism)
Analog of fibrinogen
GP IIb/IIIa (integrin) inhibitor –> inhibits platelet aggregation
Tirofiban (2 uses)
Unstable angina
Percutaneous transluminal coronary angioplasty
Tirofiban (2 side effects)
Thrombocytopenia, bleeding
Streptokinase (mechanism)
Binds free plasminogen to activate it (plasminogen doesn’t have to be bound to fibrin clots) –> gets increased plasmin
Nonfibrin-specific (unlike “-teplase”)
Streptokinase (3 uses)
Acute MI
Stroke
PE
Streptokinase (3 side effects)
Loses efficacy after initial administration (sensitized)
Allergic response
Bleeding (duh)
Methotrexate (mechanism)
Antimetabolite (S-phase specific) -> folic acid analog inhibiting DHF reductase (so decreases dTMP)
Converted to polyglutamate form after it gains access to cell to prevent movement out of cell
Methotrexate (3 categories of use)
Cancers: leukemias, lymphomas, choriocarcinoma, sarcoma
Abortion-related: abortion, ectopic pregnancy -> inhibits trophoblast division
Inflammation: RA, psoriasis, IBD
Methotrexate (4 side effects)
Myelosuppression (fixed w/ leucovorin rescue)
Hepatotoxicity (macrovesicular fatty change in liver)
Stomatitis (painful mouth ulcers) -> supplement w/ folic acid to prevent this
Teratogenic
5-fluorouracil (mechanism)
Antimetabolite (S-phase specific) - pyrimidine analog that interferes w/ folate metabolism -> inhibits thymidylate synthase (so decreases dTMP; reduced toxic effects in cells deficient in THF)
5-fluorouracil (3 uses)
Colon cancer
Pancreatic cancer
Basal cell carcinoma (topical)
5-fluorouracil (2 side effects)
Myelosuppression (not reversible w/ leucovorin!)
Photosensitivity
5-fluorouracil (antidote)
Uridine
Cytarabine (arabinofuranosyl cytidine) and gemcitabine (mechanism)
Antimetabolite (S-phase specific) - pyrimidine analog inhibiting DNA polymerase
Gemcitabine does the same thing but not S-phase specific and so more toxicity
Cytarabine (arabinofuranosyl cytidine) (2 uses)
Leukemias, lymphomas
Cytarabine (arabinofuranosyl cytidine) (side effect)
Pancytopenia (leukopenia, thrombocytopenia, megaloblastic anemia)
Azathioprine (mechanism)
Azathio”PURINE”
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis (thus also inhibits lymphocyte proliferation)
Activated by HGPRT
Azathioprine (2 categories of use)
Inflammatory: prevents organ rejection, RA, SLE, Crohn, glomerulonephritis
Cancer: leukemia
Azathioprine (4 side effects)
Bone marrow (pancytopenia), GI, liver Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)
6-mercaptopurine (mechanism)
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT
6-mercaptopurine (2 categories of use)
Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia
6-mercaptopurine (4 side effects)
Bone marrow, GI, liver (abd pain, cirrhosis, cholestasis, jaundice)
Increased toxicity w/ allopurinol (b/c its metabolism is mediated by xanthine oxidase)
6-thioguanine (mechanism)
Antimetabolite (S-phase specific) - purine analog inhibiting de novo purine synthesis
Activated by HGPRT
6-thioguanine (2 categories of use)
Inflammatory: prevents organ rejection, RA, IBD
Cancer: leukemia
6-thioguanine (3 side effects)
Bone marrow, GI, liver
Dactinomycin (actinomycin D) (mechanism)
Antitumor antibiotics - intercalates in DNA
Dactinomycin (actinomycin D) (3 uses)
Children tumors: Wilm tumor, Ewing sarcoma, rhabdomyosarcoma
Dactinomycin (actinomycin D) (side effect)
Myelosuppression
Doxorubicin (adriamycin) and daunorubicin (mechanism)
Antitumor antibiotics - generates free radicals and breaks DNA (interrupts “proper base pairing and H bond formation”)
Doxorubicin (adriamycin) and daunorubicin (3 uses)
Solid tumors, leukemias, lymphomas
Doxorubicin (adriamycin) and daunorubicin (3 side effects)
Cardiotoxicity (dilated cardiomyopathy; prevented by dexrazoxane which is iron-chelating agent) (think of D being the shape of heart)
Myelosuppression
Alopecia
Bleomycin (mechanism)
Antitumor antibiotics - generates free radicals and breaks DNA
G2 phase specific
Bleomycin (2 uses)
Testicular cancer
Hodgkin lymphoma
Bleomycin (4 side effects)
Pulmonary fibrosis (think of B being the shape of lungs)
Skin changes
Mucositis
Myelosuppression (minimal)
Cyclophosphamide (mechanism)
Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver P450
Cyclophosphamide (4 uses)
Solid tumors
Leukemia
Lymphomas
Some brain cancers
Cyclophosphamide (2 side effects)
Hemorrhagic cystitis: prevented by Mesna (binds metabolite acrolein in bladder) (think of C and Y being a bladder and urethra respectively)
Myelosuppression
Ifosfamide (mechanism)
Alkylating agent - covalently X-linked (interstrand) at guanine N-7
Requires activation by liver
Ifosfamide (4 uses)
Solid tumors
Leukemia
Lymphomas
Some brain cancers
Ifosfamide (2 side effects)
Hemorrhagic cystitis (C=C): prevented by Mesna (binds metabolite acrolein in bladder) Myelosuppression
“-mustine” (mechanism and CNS penetration)
Nitrosoureas: carmustine, lomustine, semustine
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB
“-mustine” (use)
Brain tumors (incl glioblastoma multiforme)
“-mustine” (side effect)
CNS toxicity (convulsions, dizziness, ataxia)
Streptozocin (mechanism and CNS penetration)
Nitrosourea too
Alkylating agent - X-links DNA
Requires bioactivation
Crosses BBB
Streptozocin (use)
Brain tumors (incl glioblastoma multiforme)
Streptozocin (side effect)
CNS toxicity (convulsions, dizziness, ataxia)
Busulfan (mechanism)
Alkylating agent - X-links DNA
Busulfan (2 uses)
CML
Ablate bone marrow before transplantation
Busulfan (3 side effects)
Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation
“Vin-“ (mechanism)
Vincristine, vinblastine
Inhibits microtubule formation (M-phase specific)
“Vin-“ (3 uses)
Solid tumors
Leukemias
Lymphomas
“Vin-“ (3 side effects)
Vincristine: neurotoxicity (think of V being arms and legs and representing peripheral neuropathy), paralytic ileus
Vinblastine: myelosuppression
Paclitaxel and other taxols (mechanism)
Inhibits microtubule disassembly (M-phase specific) so anaphase can’t occur
Paclitaxel and other taxols (2 uses)
Ovarian and breast carcinomas
Elution of coronary artery stents -> inhibits intimal hyperplasia -> prevents thrombosis and restenosis
Paclitaxel and other taxols (3 side effects)
Myelosuppression
Alopecia
Hypersensitivity
“-platin” (mechanism)
Cisplatin, carboplatin
X-link DNA
“-platin” (4 uses)
Testicular, bladder, ovary, lung carcinomas
“-platin” (2 side effects)
Nephrotoxicity (prevents w/ amifostine, which is a free radical scavenger, and chloride diuresis) (think of C for cysplatin and carboplatin being the shape of kidneys)
Acoustic nerve damage (think of C as ears)
“-poside” (mechanism)
Etoposide, teniposide
Inhibits topoisomerase II (S and G2 phase)
“-poside” (3 uses)
Solid tumors (esp testicular and small cell lung cancer)
Leukemias
Lymphomas
“-poside” (3 side effects)
Myelosuppression
GI irritation
Alopecia
“-tecan” (mechanism)
Irinotecan, topotecan
Inhibits topoisomerase I
“-tecan” (3 uses)
Colon cancer (irinotecan) Ovarian cancer (topotecan) Small cell lung cancer (topotecan)
“-tecan” (2 side effects)
Severe myelosuppression
Diarrhea
Hydroxyurea (mechanism)
Inhibits ribonucleotide reductase (S-phase specific)
Hydroxyurea (3 uses)
Melanoma
Myeloproliferative disorders: CML, PV (2nd line after phlebotomy)
Sickle cell disease (to increase HbF)
Hydroxyurea (2 side effects)
Bone marrow suppression
GI upset
“Predni-“ (mechanism)
Prednisone, prednisolone
Glucocorticoids, trigger apoptosis (work on nondividing cells as well)
“Predni-“ (2 categories of use)
Cancer (in combination regimen): CLL, non-Hodgkin lymphomas
Immunosuppression
“Predni-“ (side effect)
Cushing-like sx (incl psychosis and peptic ulcers)
Trastuzumab (mechanism)
Monoclonal Ab against HER-2 (c-erbB2)
Trastuzumab (2 uses)
HER-2 positive breast cancer and gastric cancer
Trastuzumab (side effect)
Cardiotoxicity (“HEARTceptin” for Herceptin)
Imatinib (mechanism and 2 uses)
Tyrosine kinase inhibitor of bcr-abl (CML) and c-kit (GI stromal tumors)
Imatinib (side effect)
Fluid retention
Rituximab (mechanism)
Monoclonal Ab against CD20
Rituximab (3 uses)
Non-Hodgkin lymphoma (follicular lymphoma)
RA (w/ methotrexate)
ITP
Rituximab (side effect)
Increased risk of progressive multifocal leukoencephalopathy
Vemurafenib (mechanism)
Inhibits B-Raf kinase w/ V600E mutation
Vemurafenib (use)
Metastatic melanoma
Bevacizumab (mechanism)
Monoclonal Ab against VEGF (so inhibits angiogenesis)
Bevacizumab (4use)
Colorectal cancer
Metastatic renal cell carcinoma
Recurrent GBM
Metastatic NSCLC
Bevacizumab (2 side effects)
Hemorrhage
Impaired wound healing
Cyclosporin (mechanism)
Calcineurin inhibitor (binds cyclophilin and blocks T cell activation by preventing IL-2 TRANSCRIPTION)
Cyclosporin (3 uses)
Transplant rejection prophylaxis
Psoriasis
RA
Cyclosporin (side effects)
Nephrotoxicity HTN, HLD, hyperglycemia Tremor Hirsutism (difference from tacrolimus) Gingival hyperplasia (difference from tacrolimus)
Tacrolimus (mechanism)
Calcineurin inhibitor (binds FKBP and blocks T cell activation by preventing IL-2 TRANSCRIPTION)
Tacrolimus (use)
Transplant rejection prophylaxis
Tacrolimus (side effects)
Nephrotoxicity
HTN, HLD, hyperglycemia
Tremor
Increased risk of DM and neurotoxicity (difference from cyclosporin)
Sirolimus (Rapamycin) (mechanism)
mTOR inhibitor (binds FKBP like tacrolimus, blocks T cell activation and B cell differentiation by preventing IL-2 SIGNAL TRANSDUCTION)
Sirolimus (Rapamycin) (use)
Kidney transplant rejection prophylaxis
Sirolimus (Rapamycin) (side effects)
Not nephrotoxic (like tacrolimus) Blood counts go down: anemia, thrombocytopenia, leukopenia Insulin resistance, HLD
Basiliximab (mechanism)
Monoclonal Ab blocking IL-2R
Basiliximab (use)
Kidney transplant rejection prophylaxis
Basiliximab (3 side effects)
Edema
HTN
Tremor
Glucocorticoids (mechanism)
Inhibits NF-KB (suppresses both B and T fx by decreasing transcription of cytokines)
Glucocorticoids (2 uses)
Transplant rejection phophylaxis
Other autoimmune disorders and inflammation
Epoetin alfa (mechanism and use)
Erythropoietin
For anemia esp in renal failure
Oprelvekin (mechanism and use)
IL-11
For thrombocytopenia
Filgrastim (mechanism and use)
GC-SF
For recovery of bone marrow
Sargramostim (mechanism and use)
GMC-SF
For recovery of bone marrow
Aldesleukin (mechanism and 2 uses)
IL-2
For renal cell carcinoma, metastatic melanoma
Alemtuzumab (mechanism and use)
Ab against CD52 -> directly cytotoxic thru complement fixation and Ab-dependent, cell-mediated cytotoxicity
For CLL
Cetuximab (mechanism and 4 uses)
Ab against EGFR
For stage IV colorectal cancer, head and neck cancer, pancreatic cancer, NSCLC
Infliximab (mechanism and 4 uses)
Ab against TNF-a
For IBD, RA, ankylosing spondylitis, psoriasis
Adalimumab (mechanism and 4 uses)
Ab against TNF-a
For IBD, RA, ankylosing spondylitis, psoriasis
Natalizumab (mechanism)
Ab against alpha4-integrin (leukocyte adhesion impaired)
Natalizumab (2 uses)
MS, Crohn
Natalizumab (side effect)
Risk of PML in pts w/ JC virus
Denosumab (mechanism and use)
Ab against RANKL For osteoporosis (inhibits osteoclast maturation by mimicking osteoprotegrin)
Omalizumab (mechanism and use)
Ab against IgE
For allergic asthma (prevents it from binding to FceRI)
Vemurafenib (mechanism and use)
BRAF kinase inhibitor
For melanoma w/ BRAF V600E mutation
Dexrazoxane (mechanism and use)
Iron-chelating agent
Used to prevent doxorubicin cardiotoxicity
OKT3 (mechanism and use)
Anti-CD3 (so anti T cells)
Used to reduce acute rejection of liver, heart, kidney
Argatroban (mechanism and use)
Direct thrombin inhibitor
Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis or HIT)
Bivalirudin and other hirudin derivatives (mechanism and use)
Direct thrombin inhibitor
Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis)
Aminocaproic acid (mechanism and 2 uses)
Blocks activation of plasminogen
Used as anidote for thrombolytics, and for disorder of fibrinolysis (radical prostatectomy and cirrhosis of liver)
Cladribine (2-CDA) (mechanism and use)
Purine analog resistant to degradation by adenosine deaminase
Penetrates CNS well, excreted in urine unchanged
DOC for hairy cell leukemia
Desmopressin acetate (DDAVP) (mechanism and 2 uses)
Stimulates endothelial cells (so release factor VIII and vWF)
Use in vWF disease and mild-moderate hemophilia A
Bortezomib (mechanism and 2 uses)
Proteasome inhibitor
For MM and Waldenstrom macroglobulinemia
Gardos channel blockers (mechanism and use)
Ca2+-dependent K+ channel blocker
Prevent intracellular dehydration -> reduces polymerization in sickle cell
Fludarabine (mechanism and use)
Deamination-resistant purine nucleotide analog
For CLL
Lepirudin (mechanism and use)
Direct thrombin inhibitor
Anti-clotting in pt that you can’t use heparin or warfarin on (for fear of skin necrosis or HIT)