Term
| Inhibit nucleotide synthesis |
|
Definition
Methotrexate, 5-FU: decrease thymidine synthesis
6-MP: decrease purine synthesis |
|
|
Term
|
Definition
Alkylating agents, cisplatin: cross link DNA
Dactinomycin, doxorubicin: intercalate DNA
Etoposide: inhibits topoisomerase II |
|
|
Term
| Interfere with cellular division |
|
Definition
Vinca alkaloids: inhibit microtubule formation
Paclitaxel: inhibits microtubule disassembly |
|
|
Term
| Vinca alkaloids and taxols inhibit what part of the cell cycle? |
|
Definition
Mitosis
interfere with microtubules |
|
|
Term
| Antimetabolites interfere with what part of the cell cycle? |
|
Definition
|
|
Term
| Etoposides interfere with what part of the cell cycle? |
|
Definition
S- DNA synthesis
G2 - synthesis of components needed for mitosis
inhibits topoisomerase II |
|
|
Term
| Bleomycin interferes with what part of the cell cycle? |
|
Definition
| G2 - synthesis of components needed for mitosis |
|
|
Term
| S-phase specific folic acid analog |
|
Definition
|
|
Term
|
Definition
S-phase specific antimetabolite
Folic acid analog
Inhibits dihydrofolate reductase, decreasing dTMP
Which decreases DNA/Protein synthesis |
|
|
Term
|
Definition
| folinic acid used to rescue myelosuppression caused by methotrexate |
|
|
Term
| Drug used with methotrexate to rescue myelosuppression |
|
Definition
| leucovorin (folinic acid) |
|
|
Term
|
Definition
myelosuppression (rescue with leucovorin)
Macrovesicular fatty change in liver
Mucositis (mouth sores) |
|
|
Term
| Clinical use of methotrexate |
|
Definition
Leukemias, lymphomas
choricarcinomas, sarcomas
abortion, ectopic pregnancy
RA, psoriasis |
|
|
Term
| S-phase specific pyrimidine analog |
|
Definition
|
|
Term
|
Definition
s-phase specific antimetabolite
pyrimidine analog bioactivated to 5F-dUMP (which covalently complexes folic acid)
Inhibits thymidylate synthase, decreasing dTMP
same effect as methotrexate |
|
|
Term
| Toxicity of 5-fluorouracil |
|
Definition
myelosuppression (not reversible with leucovorin)
photosensitivity
rescue with thymidine |
|
|
Term
| Clinical use of 5-flurouracil |
|
Definition
colon cancer and some other solid tumors
basal cell carcinoma (topical)
synergy with MTX |
|
|
Term
| Blocks de novo purine synthesis |
|
Definition
6-mercaptopurine
activated by HGPRTase |
|
|
Term
|
Definition
| blocks de novo purine synthesis, activated by HGPRTase |
|
|
Term
| Toxicity of 6-mercaptopurine |
|
Definition
BM, GI, liver
metabolized by xanthin oxidase so toxicity increases with allopurinol |
|
|
Term
| What drug interaction increases toxicity of 6-mercaptopurine and why? |
|
Definition
6-MP is metabolized by xanthine oxidase
allopurinol inhibits this enzyme and increases 6MP toxicity |
|
|
Term
| 6-mercaptopurine clinical use |
|
Definition
| Leukemias, lymphomas (not CLL or Hodgkins) |
|
|
Term
| Inhibits DNA polymerase by looking like cytidine and causing chain termination |
|
Definition
|
|
Term
|
Definition
| inhibits DNA polymerase by looking like cytidine and causing chain termination |
|
|
Term
|
Definition
| leukopenia, thrombocytopenia, megaloblastic anemia |
|
|
Term
| Clinical use of cytarabine |
|
Definition
|
|
Term
|
Definition
Cyclophosphamide, ifosfamide
Cisplatin, carboplatin
Melphalan |
|
|
Term
| Cyclophosphamide, ifosfamide |
|
Definition
| alkylating agents, covalently cross link DNA at guanine N-7, require bioactivation by liver |
|
|
Term
| Toxicity of cyclophosphamide, ifosfamide |
|
Definition
myelosuppression
hemorrhagic cysitis |
|
|
Term
| What drug causes hemorrhagic cystitis? |
|
Definition
Cyclophosphamide, ifosfamide (DNA cross linkers)
due to the breakdown product acroline, can partially prevent this side effect with mesna which binds and clears acroline |
|
|
Term
| Clinical use of cyclophosphamide |
|
Definition
NHL,
breast and ovarian carcinomas
also, immunosuppressants |
|
|
Term
| Alkylate DNA and can be used for CNS treatment |
|
Definition
Nitrosoureas
Carmustine, lomustine, semustine, streptozocin |
|
|
Term
|
Definition
alkylate DNA, require bioactivation
cross BBB (treat CNS)
includes: carmustine, lomustine, semustine, streptozocin |
|
|
Term
|
Definition
| CNS toxicity (dizziness, ataxia) |
|
|
Term
| Clinical use of Nitrosoureas |
|
Definition
brain tumors (including glioblastoma multiforme)
alkylate DNA, require bioactivation, cross BBB |
|
|
Term
| Cross links DNA, SE = nephrotoxicity and acoustic nerve damage |
|
Definition
|
|
Term
|
Definition
cross links DNA, toxic throughout cell cycle
SE: nephrotoxicity, acoustic nerve damage |
|
|
Term
| Clinical use of cisplatin |
|
Definition
testicular, bladder, ovary, lung carcinomas
cross links DNA |
|
|
Term
|
Definition
| Nephrotoxicity and acoustic nerve damage |
|
|
Term
|
Definition
|
|
Term
|
Definition
CML
ablating BM for SC transplant |
|
|
Term
|
Definition
CML
ablating BM for SC transplant |
|
|
Term
|
Definition
| pulmonary fibrosis, hyperpigmentation |
|
|
Term
| Doxorubicin, adriamycin, daunorubicin mechanism |
|
Definition
Intercalate in DNA (noncovalently) --> creates breaks in DNA strand, decreasing replication
generate free radicals
look like chicken wire |
|
|
Term
| Noncovalently intercalate in DNA, interfering with DNA replication |
|
Definition
| doxorubicin, daunorubicin |
|
|
Term
| Clinical use of doxo/daunorubicin |
|
Definition
part of ABVD for Hodgkin
myelomas, sarcomas, solid tumors
intercalate in DNA |
|
|
Term
| Toxicity of doxo/daunorubicin |
|
Definition
cardiotoxicity
Vessicant - blisters
mucositis
toxic extravasation
myelosuppression, alopecia |
|
|
Term
| intercalates in DNA, treats childhood cancers |
|
Definition
| Dactinomycin (actinomycin D) |
|
|
Term
| Clinical use of dactinomycin |
|
Definition
Wilm's tumor
Ewing sarcoma
Rhabdomyosarcoma
intercalates in DNA |
|
|
Term
|
Definition
induces formation of free radicals, causing breaks in DNA strands
which other drug generates free radicals? doxorubicin |
|
|
Term
|
Definition
pulmonary fibrosis (also seen with busulfan)
skin changes
minimal myelosuppression |
|
|
Term
|
Definition
| inhibits Ribonucleotide Reductase, decreasing DNA synthesis (S-phase specific) |
|
|
Term
| Inhibits ribonucleotide reductase |
|
Definition
hydroxyurea
decreases DNA synthesis during S phase |
|
|
Term
|
Definition
|
|
Term
| Clinical use of hydroxyurea |
|
Definition
melanoma
CML
sickle cell disease (increases HB F) |
|
|
Term
|
Definition
G2 phase specific
inhibits topoisomerase II
increases DNA degradation |
|
|
Term
| Clinical use of etoposide |
|
Definition
small cell carcinoma (lung and prostate)
testicular carcinoma |
|
|
Term
|
Definition
| myelosuppression, GI irritation, alopecia |
|
|
Term
|
Definition
may trigger apoptosis, working on nondividing cells too
increases proteins which inhibit antiapoptosis Bcl2 |
|
|
Term
| Most commonly used glucocorticoid in CA chemo |
|
Definition
|
|
Term
| Clinical use of prednisone |
|
Definition
CLL, HL, immunosuppressant for autoimmune
part of MOPP for HL |
|
|
Term
|
Definition
Cushing like symptoms
immunosuppression
cataracts
acne
osteoporosis
hypertension, hyperglycemia
peptic ulcers
psychosis |
|
|
Term
| Tamoxifen, raloxifene mechanism |
|
Definition
Selective estrogen receptor modulators
Receptor antagonists in breast, agonists in bone
block binding of estrogen to estrogen receptor-positive cells |
|
|
Term
| Clinical use of tamoxifen |
|
Definition
breast cancer, osteoporosis prevention
SERMs - receptor antagonists in breasts, agonists in bone |
|
|
Term
|
Definition
increase risk of endometrial carcinoma via partial agonists effects; hot flashes
raloxifene - no endometrial carcinoma because it is an endometrial antagonist |
|
|
Term
|
Definition
monoclonal antibody against HER-2 (erb-B2)
helps kill breast cancer cells overexpressing HER2 |
|
|
Term
| Clinical use for trastuzumab |
|
Definition
metastatic breast cancer
monoclonal Ab to HER2, killing breast cancer cells overexpressing HER2 |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Bcr-abl (phil chrom) tyrosine kinase inhibitor |
|
|
Term
| Tyrosine kinase inhibitor |
|
Definition
| imatinib, directed towards Bcr-abl fusion |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Vincristine, vinblastine mechanism |
|
Definition
Antimitotics, M phase specific alkaloids
Bind tubulin and prevent polymerization of microtubules
no mitotic spindle formation |
|
|
Term
| Clinical use of vincristine/blastine |
|
Definition
part of MOPP (oncovin) for HL
Wilms tumor
choriocarcinoma |
|
|
Term
| Toxicity of vincristine? vinblastine? |
|
Definition
vincristine: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Vinblastine: blasts bone marrow (suppression) |
|
|
Term
| Paclitaxel, other taxols mechanism |
|
Definition
M phase specific
bind tubulin and hyperstabilize polymerized microtubules
prevents mitotic spindles from breaking down (no anaphase) |
|
|
Term
| Clinical use of paclitaxel |
|
Definition
| ovarian, breast carcinomas |
|
|
Term
|
Definition
| myelosuppression and hypersensitivity |
|
|
Term
| Hyperstabilize polymerized microtubules preventing mitotic spindle breakdown |
|
Definition
|
|
Term
| Block polymerization of microtubules |
|
Definition
|
|
Term
|
Definition
DNA cross linker
Toxicity: acute renal failure |
|
|
Term
|
Definition
| used in GVHD, prevents IL2 synthesis |
|
|
Term
|
Definition
anti CD20, enhances complement mediated killing, Fc mediated phagocytosis, NK activation
toxicities: no live vaccines, steven's johnson syndrome |
|
|
Term
|
Definition
direct proapoptotic effect
Toxicity: DVT, PE, steven johnson's syndrome |
|
|
Term
Activates antithrombin III
drug? downstream effect? |
|
Definition
Heparin
decreased thrombin and Xa
short T1/2 |
|
|
Term
| Anticoagulant safe for pregnancy |
|
Definition
Heparin (activates antithrombin, decreasing thrombin and Xa)
does not cross placenta |
|
|
Term
| Test needed to monitor heparin? |
|
Definition
PTT
(heparin activates antithrombin, decreasing thrombin and Xa) |
|
|
Term
| Rapid reversal of heparinization |
|
Definition
| protamine sulfate (+ charged molecule, acts by binding - charged heparin) |
|
|
Term
| Difference between heparin and enoxaparin? |
|
Definition
enoxaparin - low molecular weight heparin
acts more on Xa, have better bioavailability, 2-4X longer half life
administered subQ and without lab monitoring
not easily reversible |
|
|
Term
|
Definition
1. heparin binds to platelets
2. causes autoantibody production that destroys platelets and overactivates remaining ones
3. thrombocytopenia, hypercoagulable state |
|
|
Term
| Directly inhibit thrombin |
|
Definition
lepirudin, bivalirudin (Hirudin derivatives)
used as alternative to heparin for anticoag in patients with HIT |
|
|
Term
|
Definition
1. heparin binds to platelets
2. causes autoantibody production that destroys platelets and overactivates remaining ones
3. thrombocytopenia, hypercoagulable state |
|
|
Term
| Directly inhibit thrombin |
|
Definition
lepirudin, bivalirudin (Hirudin derivatives)
used as alternative to heparin for anticoag in patients with HIT |
|
|
Term
| Directly inhibit thrombin |
|
Definition
lepirudin, bivalirudin (Hirudin derivatives)
used as alternative to heparin for anticoag in patients with HIT |
|
|
Term
| Drug used to anti coagulate in patient with HIT? |
|
Definition
Lepirudin, bivalidrudin (hirudin derivatives)
direct thrombin inhibitors |
|
|
Term
|
Definition
interferes with normal synthesis and y-carboxylation of vit K dependent clotting factors II, VII, IX, and X and proteins C and S
metabolized by P-450 |
|
|
Term
| Expected lab abnormality with warfarin use? |
|
Definition
| Increased PT (extrinsic pathway) |
|
|
Term
| Which has a longer half life: heparin or warfarin? |
|
Definition
| Warfarin - used in long term anticoagulation |
|
|
Term
| Anticoagulant used in pregnant woman? |
|
Definition
| Heparin - does not cross placenta |
|
|
Term
| What is monitored in Warfarin administration? |
|
Definition
|
|
Term
|
Definition
bleeding
teratogenic
skin/tissue necrosis
drug-drug interaction |
|
|
Term
| How is Heparin administered? Warfarin? |
|
Definition
Heparin - parenteral (IV, SC)
Warfarin - oral |
|
|
Term
| Treatment of warfarin overdose? |
|
Definition
|
|
Term
| Treatment for early MI or early ischemic stroke? |
|
Definition
| Thrombolytics (streptokinase, urokinase, tPA, APSAC) |
|
|
Term
| Who is thrombolytics contraindicated in? |
|
Definition
1. patients with active bleeding
2. history of intracranial bleeding
3. recent surgery
4. known bleeding diatheses
5. severe hypertension |
|
|
Term
| Directly or indirectly aid conversion of plasminogen to plasmin |
|
Definition
Thrombolytics
plasmin cleaves thrombin and fibrin clots
increased PT, PTT, no change in platelet count |
|
|
Term
| Used to treat toxicity of thrombolytics |
|
Definition
| Aminocaproic acid (inhibitor of fibrionlysis) |
|
|
Term
| Which thrombolytic has to be activated? |
|
Definition
|
|
Term
Acetylates and irreversibly inhibits COX
drug? effect? |
|
Definition
Aspirin
prevents conversion of arachiodonic acid to thromboxane A2
increased bleeding time, no effect on PT or PTT |
|
|
Term
| Mode of action for aspirin |
|
Definition
| acetylates, irreversibly inhibits COX (1 and 2), preventing conversion of arachiodonic acid to thromboxane A2 (a vasoconstrictor and enhancer of platelet aggregation) |
|
|
Term
|
Definition
1. gastric ulcers
2. bleeding
3. hyperventilation
4. Reye's syndrome
5. tinnitus (CN VIII) |
|
|
Term
Irreversibly blocks ADP receptors; prevents gpIIb/IIIa expression
drug? downstream effect? |
|
Definition
Clopidogrel, ticlopidine
1. irreversible blocking of ADP receptors --> inhibits platelet aggregation
2. preventing gpIIb/IIIa expression -->inhibit fibrinogen binding |
|
|
Term
| Effect of clopidogrel/ticlopidine on stroke? |
|
Definition
| decreases incidence or recurrence of thrombotic stroke |
|
|
Term
|
Definition
Neutropenia
(inhibits platelet aggregation and fibrinogen binding) |
|
|
Term
| Monoclonal Ab that binds to gpIIb/IIIa on activated platelets |
|
Definition
Abciximab
prevents platelet aggregation |
|
|
Term
|
Definition
| bleeding, thrombocytopenia |
|
|
Term
| Stimulates release of FVIII and vWF from endothelial cells |
|
Definition
|
|
