UPDATED Unit 1 Deck

Question 1

alkalating agents

Answer 1

• produce strong electrophiles through carbonium or ethyleneimonium intermediates, which covalently bond via alkylation of nucleophilic moieties in DNA (mostly N7 position of guanine); Cell Cycle Non-Specific (CCNS)
• side effects: bone marrow, mucosal toxicity, nausea and vomiting, toxic effects on reproductive systems, increased leukemia risk
• resistance may occur due to decreased permeability or uptake; increased rates of catabolism; enhanced DNA repair; increased glutathione production (inactivates via conjugation)
• classes: nitrogen mustards, nitrosoureas, triazenes, platinum analogs

Question 2

Mechlorethamine (Mustargen)

Answer 2

• alkalating agent; class: nitrogen mustard
• mechanism: spontaneous conversion to active metabolites in body fluids or enzymatically converted in liver
• treats: hodgkin’s disease, topically for treatment of cutaneous T-cell lymphoma
• other side effects: severe nausea and vomiting, myelosuppression (leucopenia, thrombocytopenia)
• don’t use much anymore due to sterility

Question 3

Cyclophosphamide (Cytoxan)

Answer 3

• alkalatin agent; class: nitrogen mustard
• mechanism: conversion by hepatic cytochrome P450 to active metabolite phosphoramide mustard
• treats: most widely used alkylating agent (broad clinical spectrum); singly or in combination for ALL, CLL, non-Hodgkin’s lymphoma, and breast, lung, and ovarian cancer
• important side effects: hemorrhagic cystitis (bladder irritation) due to acrolein (toxic drug metabolite); adequate hydration and administration of MESNA (2-mercaptoethane sulfonate) minimizes problem
• other side effects: nausea, vomiting, myelosuppression
• relatively long plasma half-life (7-15 hrs); PO

Question 4

Ifosfamide (Ifex)

Answer 4

• alkylating agent; class: nitrogen mustard
• mechanism: conversion by hepatic cytochrome P450 to active metabolite phosphoramide mustard
• treats: sarcoma and testicular cancer
• important side effects: hemorrhagic cystitis (bladder irritation) due to acrolein (toxic drug metabolite); adequate hydration and administration of MESNA (2-mercaptoethane sulfonate) minimizes problem
• other side effects: nausea, vomiting, myelosuppression
• relatively long plasma half-life (7-15 hrs); PO

Question 5

Carmustine (Gliadel)

Lomustine (Ceenu)

Answer 5

• alkylating agent; class: nitrosureas
• mechanism: alkylating agent
• treats: brain tumors (cross blood-brain barrier)
• important side effects: renal toxicity, pulmonary fibrosis
• other side effects: profound myelosuppression, severe nausea and vomiting

Question 6

Dacarbazine (DTIC)

Answer 6

• alkylating agent; class: triazenes
• mechanism: prodrug activated by liver cytochromes
• treats: part of ABVD for Hodgkin’s disease; also, malignant melanoma
• other side effects: nausea and vomiting, myelosuppression (neutropenia, thrombocytopenia), flu-like symptoms (fever, fatigue)
• IV administration

Question 7

Procarbazine (Matulane)

Answer 7

• alkylating agent; class: triazenes
• mechanism: forms free radicals
• treats: hodgkin’s lymphoma
• important side effects: may cause leukemia

Question 8

Temozolomide (Temodar)

Answer 8

• alkylatin agent; class: triazenes
• mechanism: nonenzymatic conversion to methylhydrazine at physiologic pH
• treats: malignant gliomas
• other side effects: nausea and vomiting, myelosuppression (neutropenia, thrombocytopenia), flu-like symptoms (fever, fatigue)
• PO

Question 9

Cisplatin (Platinol)

Answer 9

• alkylating agent; class: platinum analog
• mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA (e.g., guanine N7) and is converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links
• treats: testicular, ovarian, cervical, and bladder cancers; also useful in treatment of head and neck cancer, and lung carcinoma
• important side effects: nephrotoxicity, ototoxicity, peripheral motor and sensory neuropathy at high doses
• other side effects: severe nausea and vomiting, mild to moderate myelosuppression

Question 10

Carboplatin (Paraplatin)

Answer 10

• alkylating agent; class: platinum analog
• mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA (e.g., guanine N7) and is converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links
• treats: ovarian cancer
• other side effects: myelosuppression (thrombocytopenia)

Question 11

Oxaliplatin (Eloxatin)

Answer 11

• alkylating agent; class: platinum analog
• mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA (e.g., guanine N7) and is converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links
• treats: gastric and colorectal cancer
• important: peripheral sensory neuropathy (cold-induced)
• other side effects: neutropenia

Question 12

Methotrexate (Trexall)

Answer 12

• antimetabolite; class: folate analog
• mechanism: inhibits DHFR (converts dietary folate to THF; needed for thymidine and purine synthesis); given orally or intrathecally
• treats: childhood ALL and choriocarcinoma; combination therapy for Burkitt’s lymphoma and carcinomas of breast, ovary, head and neck, and bladder; administered intrathecally for meningeal leukemia and meningeal metastases of tumors (can’t cross BBB); high-dose for osteosarcoma
• important side effects: renal toxicity (crystallization in urine at high doses), hepatotoxicity (long-term, fibrosis/cirrhosis), reproductive (defective oogenesis or spermatogenesis, abortion)
• other side effects: bone marrow (myelosuppression, spontaneous hemorrhage); GI toxicity (oral ulceration, stomatitis)
• notes: can use leucovorin to prevent toxic effects of MTX, as healthy cells can take it up a lot better than tumor cells

Question 13

Pemetrexed (Alimta)

Answer 13

• antimetabolite; class: folate analog
• mechanism: polyglutamate forms that inhibit THF-dependent enzymes (e.g., DHFR, TS); metabolized to polyglutamate forms that inhibit THF-dependent enzymes (e.g., DHFR, thymidylate synthase (TS)
• treats: colon cancer, mesothelioma, non-small cell lung cancer, pancreatic cancer

Question 14

5-Fluorouracil (5-FU, Carac)

Answer 14

• antimetabolite; class: pyramidine analog
• mechanism: 5-FU→active metabolites: 5-FdUMP inhibits TS; 5-FdUTP incorporates into RNA & interferes with RNA function; prodrug ribosylated and phophosrylated into 5-FdUMP
• treats: combination therapy for breast, colorectal, gastric, head and neck, cervical and pancreatic cancer; topically for basal cell carcinoma
• important side effects: hand-foot syndrome (erythema, sensitivity of palms and soles), cardiac toxicity (acute chest pains)
• other side effects: anorexia and nausea; mucosal ulcerations, stomatitis, diarrhea; thrombocytopenia and anemia
• notes: leucovorin can potentiate effects of 5-FU; must be given IV (GI toxicity and rapid degradation + metabolism in gut and liver)

Question 15

Cytarabine (AraC, Depocyt)

Answer 15

• antimetabolite; class: pyramidine analog
• mechanism: Ara-C converted by deoxycytidine kinase to Ara-CMP→Ara-CTP; terminates DNA synthesis as Ara-CTP
• treats: AML (most effective treatment), ALL and blast phase CMLother side effects:
• other side effects: severe myelosuppression (leucopenia, thrombocytopenia, anemia), GI tract toxicity (ulceration, stomatitis, diarrhea)

Question 16

Gemcitabine (dFdC, Gemzar)

Answer 16

• antimetabolite; class: pyramidine analog
• mechanism: converted to active metabolites: dFdCDP inhibits ribonucleotide reductase (lowers deoxyribonucleotide); dFdCTP incorporates into DNA, terminating DNA synthesis
• treats: pancreatic cancer; effective against non-small cell lung cancer, ovarian, bladder, esophageal, and head and neck cancer
• other side effects: myelosuppression (leucopenia, thrombocytopenia, anemia), flu-like
• notes: more effective against solid tumors than cytarabine

Question 17

antimetabolites

Answer 17

• structural analogs of folic acid or of the purine/pyramidine bases found in DNA; act in S-phase (cell cycle specific)
• classes: folate, pyramidine, and purine analogs

Question 18

6-Mercaptopurine (Purinethol)

Answer 18

• antimetabolite; class: purine analog
• mechanism: prodrug metabolized by (HGPRT) to 6-thioinosinic acid (TIMP); TIMP inhibits first step of de novo purine base synthesis and the formation of AMP and xanthinylic acid from inosinic acid, reducing purine levels. As well, TIMP is converted to thio-guanine ribonucleotides, inhibiting DNA and RNA synthesis
• treats: maintain remission in acute ALL
• important side effects: hepatotoxicity in prolonged use
• other side effects: bone marrow suppression
• notes: drug interaction with allopurinol (for gout), which inhibits xanthine oxidase; decrease 6-MP dose to avoid drug accumulation and toxicities

Question 19

Dactinomycin (Actinomycin D, Cosmegen)

Answer 19

• DNA intercalating agent
• mechanism: intercalates G-C base pairs of DNA, interfering with DNA-dependant RNA polymerase; also causes ssDNA breaks
• treats: pediatric tumors (Wilms’ tumor, rhabdomyosarcoma Ewing’s sarcoma); choriocarcinoma in women
• important side effects: hematopoietic suppression with pancytopenia
• other side effects: anorexia, nausea, vomiting

Question 20

Daunorubicin (Cerubidine)

Idarubicin (Idamycin)

Answer 20

• DNA intercalating agent; class: anthracyclines
• mechanism: intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2→ cleaved in the presence of Fe→ OH radical, which cleaves DNA
• treats: AML
• important side effects: irreversible dose-dependent cardiotoxicity; alopecia
• other side effects: myelosuppression (neutropenia), stomatitis, GI disturbances
• notes: dexrazoxane is cardio-protective

Question 21

Doxorubicin (Adriamicin, Doxil)

Answer 21

• DNA intercalating; class: anthracycline
• mechanism: intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2→ cleaved in the presence of Fe→ OH radical, which cleaves DNA
• treats: sarcomas, breast and lung carcinomas, malignant lymphomas
• important side effects: irreversible dose-dependent cardiotoxicity; alopecia
• other side effects: myelosuppression (neutropenia), stomatitis, GI disturbances
• notes: dexrazoxane is cardio-protective

Question 22

Epirubicin (Ellence)

Answer 22

• DNA intercalating; class: anthracycline
• mechanism: intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2→ cleaved in the presence of Fe→ OH radical, which cleaves DNA
• treats: metastatic breast cancer, gastric cancer
• important side effects: irreversible dose-dependent cardiotoxicity; alopecia
• other side effects: myelosuppression (neutropenia), stomatitis, GI disturbances
• notes: dexrazoxane is cardio-protective

Question 23

DNA Intercalating Agents

Answer 23

• bind DNA through intercalation between specific bases, blocking DNA, RNA or both synthesis; cause DNA strands to break and interfere with cell replication; CCNS
• “cins”

Question 24

Bleomycin (Blenoxane)

Answer 24

• DNA intercalating
• mechanism: acts in G2 phase of cell cycle (binds to DNA, producing ss- and dsDNA breaks)
• treats: combination therapy for testicular tumors or Hodgkin’s disease; squamous cell carcinomas and lymphomas
• important side effects: pulmonary toxicity (pulmonary fibrosis); cutaneous toxicity (hyperpigmentation, hyperkeratosis, erythema); hyperthermia
• other side effects: minimally myelo- and immunosuppressive (often used in combo therapy); headache, nausea, vomiting
• notes: dexrazoxane is cardio-protective

Question 25

microtubule inhibitors

Answer 25

• Inhibit mitosis and cause metaphase arrest by interfering with microtubule function (tubulin (de)polymerization); CCS
• classes: vinca alkaloids, taxanes,

Question 26

Vinblastine (Velban)

Answer 26

• MT inhibitor; class: vinca alkaloid
• mechanism: blocks tubulin polymerization into MTs
• treats: metastatic testicular tumors (with bleomycin, cisplatin); component of ABVD used for Hodgkin’s disease
• other side effects: myelosuppression, nausea, vomiting

Question 27

Vincristine (Oncovin)

Answer 27

• MT inhibitor; class: vinca alkaloid
• mechanism: blocks tubulin polymerization into MTs
• treats: Childhood ALL (with glucocorticoids); Hodgkin’s and non-Hodgkin’s lymphomas
• important side effects: dose-limiting neurotoxicity (peripheral neuropathy)
• other side effects: relatively low bone marrow toxicity

Question 28

Paclitaxel (Taxol, Abraxane)

Answer 28

• MT inhibitor; class: taxane
• mechanism: block MT depolymerization into tubulin
• treats: metastatic breast, ovarian, lung, and head and neck cancers
• important side effects: peripheral neuropathy
• other side effects: neutropenia; hypersensitivity reactions

Question 29

Docetaxel (Taxotere)

Answer 29

• MT inhibitor; class: taxane
• mechanism: block MT depolymerization into tubulin
• treats: metastatic breast, ovarian, lung, and head and neck cancers
• important side effects: peripheral neuropathy
• other side effects: neutropenia; hypersensitivity reactions

Question 30

topoisomerase inhibitors

Answer 30

• prevent the resealing of topo I (ssDNA) and topo II (dsDNA); CCS
• classes: epipodophyllotoxins, camptothecin analogs

Question 31

Etoposide (Etopophos)

Answer 31

• topoisomerase inhibitor; class: epipodophyllotoxin
• mechanism: inhibits topoisomerase II
• treats: testicular carcinoma, lung cancer, and non-Hodgkin’s lymphoma
• other side effects: dose-limiting myelosuppression (neutropenia), oral mucositis

Question 32

Teniposide (Vumon)

Answer 32

• topoisomerase inhibitor; class: epipodophyllotoxin
• mechanism: inhibits topoisomerase II
• treats: ALL
• other side effects: dose-limiting myelosuppression (neutropenia), oral mucositis

Question 33

Irinotecan (Camptosar)

Answer 33

• topoisomerase inhibitor; class: camptothecin analog
• mechanism: inhibits topoisomerase I
• treats: advanced colorectal cancer; lung, ovarian, cervical and brain tumors
• other side effects: severe neutropenia, severe diarrhea

Question 34

Topotecan (Hycamtin)

Answer 34

• topoisomerase inhibitor; class: camptothecin analog
• mechanism: inhibits topoisomerase I
• treats: ovarian and small cell lung cancer
• other side effects: severe neutropenia, severe diarrhea

Question 35

hormone therapy

Answer 35

• used in the treatment of hormone-dependent neoplasms
• classes: glucocorticoids, SERMs, SERDs, aromatase inhibitors, GnRH blockers, nonsteroidal androgen receptor blockers

Question 36

Prednisone (Meticorten)

Answer 36

• hormone therapy; class: glucocorticoid
• mechanism: inhibit mitosis in lymphocytes
• treats: ALL; combination for Hodgkin’s, non-Hodkin’s, multiple myeloma, and CLL

Question 37

Dexamethasone (Decadron)

Answer 37

• hormone therapy; class: glucocorticoid
• mechanism: inhibit mitosis in lymphocytes
• treats: reduces edema in brain and spinal cord tumors with radiation therapy

Question 38

Tamoxifen (Soltamox)

Answer 38

• hormone therapy; class: SERM
• mechanism: competes with estradiol for binding to estrogen receptor
• treats: ER+breast cancer, or as adjuvant therapy following primary breast tumor excision; prevention of breast cancer in high-risk patients
• important side effects: hot flushes, hair loss; increased risk of endometrial cancer; increased risk of thromboembolic events
• other side effects: nausea and vomiting

Question 39

Fulvestrant (Faslodex)

Answer 39

• hormone therapy; class: SERD
• mechanism: binds with much higher affinity (>100-fold) to estrogen receptor than tamoxifen, inhibiting dimerization, increasing degradation, and reducing overall ER levels
• treats: posmenopausal women with ER+ metastatic breast cancer

Question 40

Aminoglutethamide (Cytadren)

Answer 40

• hormone therapy; class: aromatase inhibitor
• mechanism: inhibits function of aromatase
• treats: relatively weak, used against breast cancer
• important side effects: significant

Question 41

Anastrozole (Arimidex)

Answer 41

• hormone therapy; class: aromatase inhibitor
• mechanism: inhibits function of aromatase
• treats: First-line for ER+ breast cancer in postmenopausal women

Question 42

Letrozole (Femara)

Answer 42

• hormone therapy; class: aromatase inhibitor
• mechanism: inhibits function of aromatase
• treats: ER+ breast cancer in postmenopausal women

Question 43

Exemestane (Aromasin)

Answer 43

• hormone therapy; class: aromatase inhibitor
• mechanism: Steroidal inhibitor of aromatase
• treats: ER+ breast cancer in postmenopausal women

Question 44

Leuprolide (Lupron)

Goserelin (Zoladex)

Answer 44

• hormone therapy; class: GnRH analog
• mechanism: binds GnRH receptor; inhibits release of FSH & LH
• treats: androgen ablation therapy, along with AR blockers

Question 45

Flutamide (Eulexin)

Bicalutamide (Casodex)

Answer 45

• hormone therapy; class: nonsteroidal androgen-receptor blockers
• mechanism: competes with androgen for AR binding
• treats: androgen ablation therapy, along with GnRH blockers

Question 46

Imatinib (Gleevac)

Answer 46

• tyrosine kinase inhibitor
• mechanism: inhibits Abl kinase by binding where ATP should go; also inhibits PDGFR and c-kit; metabolized by cyt P450
• treats: first line therapy for CML; also, gastrointestinal tumor (GIST)
• important side effects: nausea and vomiting, fluid retention, muscle cramps, arthralgia
• other side effects:
• notes: myelosuppression; 1 PO QDay

Question 47

Gefitinib (Iressa)

Erlotinib (Tarceva)

Answer 47

• tyrosine kinase inhibitor
• mechanism: inhibit epidermal growth factor receptor (EGFR) tyrosine kinase
• treats: non-small cell lung cancer

Question 48

Nilotinib (Tasigna)

Answer 48

• tyrosine kinase inhibitor
• mechanism: inhibits Abl kinase
• treats: imatinib-resistant CML
• important side effects: myelosuppression
• other side effects: QT prolongation, hepatotoxicity, electrolyte abnormalities
• notes: 2 PO QDay

Question 49

Dasatinib (Sprycel)

Answer 49

• tyrosine kinase inhibitor
• mechanism: inhibits Abl & Src kinases
• treats: imatinib-resistant CML
• important side effects: myelosuppression, bleeding, fluid retention, pulmonary arterial hypertension
• other side effects: diarrhea, nausea and vomiting, weakness, infections
• notes: 1 PO QDay

Question 50

Rituximab (Rituxan)

Answer 50

• monoclonal antibody
• mechanism: CD20 B-cell antibody that can directly activate apoptosis, activate complement, or activate cell-mediated cytotoxicity (e.g., T cells, NK cells)
• treats: non-Hodgkin’s lymphomas
• important side effects: infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML)
• other side effects: skin reactions, irregular heartbeat, muscle or joint pain
• notes: patients need careful monitoring

Question 51

Trastuzumab (Herceptin)

Answer 51

• monoclonal antibody
• mechanism: unknown HER2/neu (ErbB2) receptor antibody mechanism (enhanced receptor endocytosis or blocking homo- or heterodimerization)
• treats: HER2/neu-overexpressing metastatic breast cancer
• important side effects: hypersentivity reaction; ventricular dysfunction
• notes: usually combined with taxanes; enhances doxorubicin cardiotoxicity

Question 52

Cetuximab (Erbitux)

Answer 52

• monoclonal antibody
• mechanism: EGFR1 (ErbB1)
• treats: EGFR+ metastatic colorectal cancer
• important side effects: allergic reactions, sudden cardiac death, dermatologic problems, infections, renal failure, electrolyte abnormalities
• other side effects: asthenia/malaise, fever, nausea, constipation, interstitial pneumonitis
• notes: clinical trials, probably combine with cisplatin

Question 53

Ipilimumab (Yervoy)

Answer 53

• human monoclonal antibody
• mechanism: Cytotoxic T-Lymphocyte Antigen 4 inhibitor; stimulates immune system
• treats: melanoma

Question 54

Vemurafenib (Zelboraf)

Answer 54

• serine/threonine kinase inhibitor
• mechanism: inhibits oncogenic BRAF kinase
• treats: unresectable Stage III and IV or metastatic melanomas w/BRAF mutations
• important side effects: arthralgia, fatigue, photosensitivity, nausea, alopecia, diarrhea, QT prolongation
• other side effects: cutaneous SCC, keratoacanthoma, new primary cutaneous melanoma
• notes: superior to dacarbazine in Phase III trials

Question 55

Dabrafenib (Tafinlar)

Answer 55

• serine/threonine kinase inhibitor
• mechanism: inhibits oncogenic BRAF kinase
• treats: unresectable Stage III and IV or metastatic melanomas w/BRAF mutations
• important side effects: serious febrile drug reactions, uveitis and iritis, hyperglycemia, hyperkeratosis
• other side effects: higher risk of developing cutaneous SCC, keratoacanthoma, new primary cutaneous melanoma vs. vemurafenib
• notes: may cause male infertility

Question 56

Trametinib (Mekinist)

Answer 56

• mechanism: Inhibits MEK
• treats: unresectable Stage III and IV or metastatic melanomas w/BRAF mutations
• important side effects: cardiomyopathy, retinal disorders, interstitial lung disease, serious skin toxicities
• other side effects: rash, diarrhea, stomatitis, hypertension, pruritis
• notes: may cause female infertility

Question 57

Hydroxyurea (Hydrea)

Answer 57

• mechanism: inhibits ribonucleoside diphosphate reductase
• treats: CML (replaced by Imatinib), polycythemia vera, essential thrombocythemia; treatment for sickle cell disease (increases Hb-F)

Question 58

Retinoids

Answer 58

• mechanism: ATRA induces terminal differentiation in malignant immature promyelocytes, which subsequently apoptose
• treats: APL
• important side effects: “Leukocyte Activation Syndrome” (LAS), an increase in WBCs (fever, weight gain, respiratory distress, serosal effusion, renal failure)
• notes: combined w/anthracyclines; corticosteroids used to block “LAS”

Question 59

Arsenic Trioxide (Trisenox)

Answer 59

treats relapsed APL

Question 60

Thalidomide (Thalomid)

Answer 60

treats multiple myeloma and myelodysplastic syndromes

Question 61

Interferons

Answer 61

treats hairy-cell leukemia, CML, and AIDS-related Kaposi’s sarcoma

Question 62

ABVD

Answer 62

combination therapy of doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine

Question 63

CHOP

Answer 63

combination therapy of cyclophosphamide, hydroxydoxorubicin, vincristine (oncovine), prednisone

Question 64

MOPP

Answer 64

combination therapy of mechlorethamine, vincristine (oncovine), procarbazine, prednisone

Question 65

CMF

Answer 65

combination therapy of cyclophosphamide, methotrexate, 5-fluorouracil

Question 66

FEC

Answer 66

combination therapy of 5-fluorouracil, epirubicin, cyclophosphamide

Question 67

Estradiol (valerate & cypionate)

Estrone sulfate

Equilin sulfate

Answer 67

• estradiol esters (steroidal)
• mechanism: absorbed through skin, mucus membranes, GI Tract; body-wide distribution via sex-hormone binding globulin
• treats: contraception, primary hypogonadism, postmenopausal hormone therapy
• important side effects: weight gain, HTN; less commonly, may cause breast cancer, DVT, cervical and endometrial cancer
• other side effects: nausea, breast tension/pain, vaginal bleeding, headache
• notes: strongly contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeds; relatively contradinicated in pregnancy, thromboembolic disease, HTN, hepatic disease, family history of breast or uterine cancer

Question 68

Ethinyl estradiol

Mestranol

Quinestrol

Answer 68

• alkyl estrogen
• mechanism: absorbed through skin, mucus membranes, GI Tract; body-wide distribution via sex-hormone binding globulin
• used for contraception, primary hypogonadism, postmenopausal hormone therapy
• important side effects: weight gain, HTN; less commonly, may cause breast cancer, DVT, cervical and endometrial cancer
• other side effects: nausea, breast tension/pain, vaginal bleeding, headache
• notes: strongly contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeds; relatively contradinicated in pregnancy, thromboembolic disease, HTN, hepatic disease, family history of breast or uterine cancer

Question 69

Diethylstilbestrol (DES)

Answer 69

• non-steroidal synthetic estrogen
• important side effects: increased risk of clear cell adenocarcinoma of vagina & cervix

Question 70

Tamoxifen citrate (Nolvadex)

Answer 70

• non-steroidal anti-estrogen; selective estrogen receptor modifier
• mechanism: blocks estrogen from binding ER and causing growth in ER+ breast cancer
• treats: ER+ breast cancer
• important side effects: pro-estrogenic effect on uterine epithelium (increase risk of endometrial cancer); partial estrogen agonist in bone and endometrium
• notes: anti-estrogenic effect on mammary epithelium; must be used in very high doses

Question 71

Clomiphene citrate (Clomid)

Answer 71

• non-steroidal anti-estrogen
• mechanism: blocks estrogen binding to hypothalamic receptors (no estradiol negative feedback on gonadotropins)→ increased secretion of gonadotropins & LH→ovulation
• used to stimulate ovulation in patients who want to get pregnant
• important side effects: hot flashes, multiple pregnancy
• other side effects: stomach pain, headache, upset stomach, vomit
• notes: sis-isomer (zuclomiphene) is a weak estrogen agonist; trans-isomer (enclomiphene) is a potent estrogen antagonist

Question 72

Micronized progesterone

Answer 72

• natural progesterone
• mechanism: binds to PR; decreased first-pass metabolism & enhanced dissolution due to micronization
• contraception, hormone replacement therapy
• important side effects: fatigue, drowsiness
• notes: contraindicated in thromboembolic disorders or patients with such a history, liver disease (metabolised in the liver), undiagnosed vaginal bleeding, pregnancy (atrophy of endometrium leading to birth defects)

Question 73

Transvaginal progesterone

Answer 73

• natural progesterone
• mechanism: binds to PR; vaginal gel (uterine effects without first pass metabolism and minimal systemic side effects)
• used for contraception, hormone replacement therapy
• important side effects: fatigue, drowsiness
• notes: contraindicated in thromboembolic disorders or patients with such a history, liver disease (metabolised in the liver), undiagnosed vaginal bleeding, pregnancy (atrophy of endometrium leading to birth defects)

Question 74

Medroxyprogesterone

Norethindrone

Norgestrel

Megestrol

Answer 74

• synthetic progesterone
• used for contraception, hormone replacement therapy
• important side effects: Edema, abdominal bloating; less commonly: strong androgenic effects (hirsutism, acne)
• other side effects: Anxiety, irritability, depression, muscular pain; increased risk of thrombus and PE
• notes: contraindicated in thromboembolic disorders or patients with such a history, liver disease (metabolised in the liver), undiagnosed vaginal bleeding, pregnancy (atrophy of endometrium leading to birth defects)

Question 75

Monophasic Ortho-Novum

Answer 75

• combination OCP
• mechanism: constant level of estrogen suppresses FSH, LH surge; progesterone suppresses LH surge, thickens cervical mucus, leads to endometrial atrophy
• same side effects as estrogen and progesterone
• notes: consistent dose of estrogen and progestin (only take 21 days)

Question 76

Biphasic Ortho-Novum

Answer 76

• combination OCP
• mechanism: constant level of estrogen suppresses FSH, LH surge; progesterone suppresses LH surge, thickens cervical mucus, leads to endometrial atrophy
• same side effects as estrogen and progesterone
• notes: fixed estrogen, progestin increased for days 11-21

Question 77

Triphasic Ortho-Novum

Answer 77

• combination OCP
• mechanism: constant level of estrogen suppresses FSH, LH surge; progesterone suppresses LH surge, thickens cervical mucus, leads to endometrial atrophy
• same side effects as estrogen and progesterone
• notes: fixed or variable estrogen, while progestin increases in 3 phases (1-7, 8-14, 15-21)

Question 78

mini-pill

Answer 78

• progestin only OCP
• mechanism is the same as progesterone
• less effective than combination pill for contraception; use when patient has estrogen contraindication; good in lactating women (estrogen reduces milk production)
• important side effects: more likely to produce irregular menstrual cycle (estrogen required to provide stability to endometrium)
• other side effects: suppresses endometrial cancer

Question 79

Levonorgestrel (Plan B)

Answer 79

• synthetic progestogen
• mechanism of action is unknown
• prevents implantation (must be taken within 72 hours of coitus)
• side effects are likely the same as OCPs

Question 80

Mifepristone (RU-486, Korlym)

Answer 80

• anti-progestin; glucocorticoid receptor antagonist
• mechanism: competitively binds to PR (leading to detachment of fetus); glucocorticoid receptor antagonist
• used for abortion; cushing’s syndrome
• notes: must take early in pregnancy (by day 49); PO; must be given by doctor in medical facility prepared for surgery if abortion incomplete

Question 81

Sildenafil citrate (Viagra)

Vardenafil HCl (Levitra)

Tadalafil (Cialis)

Answer 81

• PDE5 inhibitor
• Bind catalytic site of PDE5; inhibits PDE5 breakdown of cGMP→ decreased Ca→ smooth muscle relaxation→ erection
• treats: ED (does not trigger an automatic erection, but improves response to sexual stimulation)
• important side effects: headache, dizziness, change in vision (NAION)
• other side effects: flushing, upset stomach, stuffy or runny nose, UTI, diarrhea
• notes: PO (once/day max); half-life of 4 hours, peak plasma concentration in 1-2 hours; contraindicated if on nitrates or α-blockers (unsafe drop in BP)

Question 82

Indomethacin (Indocin)

Naproxen (Aleve)

Answer 82

• non-selective NSAID
• mechanism: eliminate pain; reduce inflammation (does not slow disease progression)
• treats RA and acute gouty arthritis
• important side effects: gastric and uodenal ulcers

Question 83

COX-2 inhibitors

Answer 83

• selective NSAID
• mechanism: elimates pain; reduce inflammation (does not slow disease progression)
• Superseding conventional NSAIDs for RA
• important side effects: 50% fewer gastric and duodenal ulcers than traditional NSAIDs

Question 84

quinolones

Answer 84

• DMARD (antimalarial)
• mechanism: reduces T-cell activation and chemotaxis
• treats: RA, SLE
• important side effects: retinal damage (chloroquine)
• used for patients who no longer respond to NSAIDS or can’t tolerate other DMARDs

Question 85

glucocorticoids (corticosteroids)

Answer 85

• DMARD
• mechanism: inhibits phospholipase A2 (inhibiting release of arachidonic acid and, thus, formation of prostaglandins) and inhibits cytokine production (which prevents induction of COX-2)
• treats RA; acute gouty arthritis (intraarticular injection for relief of acute monoarticular gout)
• important side effects: cushingoid syndrome
• Started initially (fast acting) before other drugs become effective

Can give orally or intra-articularly

Question 86

Sulfasalazine (Azulfidine)

Answer 86

• DMARD
• mechanism: likely inhibition of IL-1 & TNF-alpha release
• treats RA
• important side effects: N/V, skin rashes, neutropenia (30% of patient discontinue drug)
• other side effects: headaches
• acts quicker than other drugs

Question 87

Methotrexate (Trexall)

Answer 87

• DMARD (immunosuppressive)
• mechanism: inhibition of aminoimidazolecarboxamide (AICAR) transformylase and thymidylate synthetase, with secondary effects on PMN chemotaxis; causes adenosine accumulation, which inhibits inflammation
• treats: RA (gold standard)
• important side effects: nausea, stomatitis, hepatotoxicity (rare)
• takes several weeks to start working

Question 88

Leflunomide (Arava)

Answer 88

• DMARD (immunosuppressive)
• mechanism: inhibits dihydroorotate dehydrogenase (DHODH), which inhibits T-lymphocyte response to stimuli
• treats RA
• important side effects: diarrhea, hepatotoxity
• takes several weeks to start working; oral prodrug

Question 89

Etanercept (Enbrel)

Answer 89

• biological response modifier
• mechanism: blocks binding of TNF to TNF receptors
• treats RA
• 2x weekly subQ injections

Question 90

Infliximab (Remicade)

Answer 90

• biological response modifier
• mechanism: blocks binding of TNF to TNF receptors
• treats RA
• important side effects: antigenic response to murine monoclonal Ab

Question 91

Adalimumab (Humira)

Answer 91

• biological response modifier
• mechanism: blocks binding of TNF to TNF receptors
• treats RA
• 2x monthly injections; fully human so no antigenic response

Question 92

Golimumab

Certolizumab

Answer 92

• biological response modifier
• mechanism: blocks binding of TNF to TNF receptors
• treats RA
• important side effects: risk of serious infection
• certolizumab is conjugated to PEG for stabilization

Question 93

Anakinra (Kineret)

Answer 93

• biological response modifier
• mechanism: IL-1 receptor antagonist
• treats RA
• short (6 hr) plasma half-life; daily treatment with high doses

Question 94

Tocilizumab (Actemra)

Answer 94

• biological response modifier
• mechanism: IL-6 receptor antagonist
• treats RA

Question 95

Rituximab (Rituxan)

Answer 95

• biological response modifier
• mechanism: anti-CD20 mAb, reduces circulating B cells
• treats RA
• important side effects: infections, hypersensitivity reactions
• used for RA refractory to TNF-alpha inhibitors

Question 96

Abatacept (Orencia)

Answer 96

• biologic response modifier
• mechanism: inhibits T-cell activation and induces T-cell apoptosis
• treats: RA
• important side effects: headaches, infections
• used in patients for RA refractory to MTX or TNF-alpha inhibitors

Question 97

Tofacitinib

Answer 97

• biologic response modifier
• mechanism: inhibition of JAK 1 & 3 which inhibits production of inflammatory mediators
• treats: RA
• important side effects: Upper respiratory tract infections; headaches, diarrhea
• other side effects: malignancies

Question 98

cochicine (Colcrys)

Answer 98

• mechanism: prevents tubulin polymerization→ inibition of leukocyte migration, phagocytosis, and release of cytokines
• treats: acute gouty arthritis
• important side effects: long-term use causes peripheral neuropathy & neutropenia
• other side effects: nausea, vomiting, abdominal pain, troublesome diarrhea
• works in 12-24 hours

Question 99

Probenecid (Benemid)

Answer 99

• uricosuric agent
• mechanism: compete with urate at anionic transport site of renal tubule and inhibit urate reabsorption
• treats: chronic tophaceous gout
• important side effects: urate crystal mobilization and acute gouty arthritis
• other side effects: GI irritation
• secretion of some weak acids (e.g., penicillin) is reduced

Question 100

Allopurinol (Zyloprim)

Answer 100

• mechanism: reduces uric acid synthesis by inhibiting xanthine oxidase (competitive inhibition)→ alloxanthine (non-competitive inhibitor of xanthine oxidase)
• treats: chronic tophaceous gout
• important side effects: acute attacks of gouty arthritis early in treatment due to mobilization of urate crystals

Question 101

Febuxostat (Uloric)

Answer 101

• mechanism: non-purine, non-competitive antagonist of xanthine oxidase
• treats: chronic tophaceous gout
• important side effects: nausea, rash, arthralgias
• $$$

Question 102

Pegloticase (Krystexxa)

Answer 102

• recombinant, stabilized uricase
• mechanism: converts uric acid to allantoin
• treats: chronic tophaceous gout

Question 103

Afatinib (Gilotrif)

Answer 103

• tyrosine kinase inhibitor
• mechanism: inhibits EGFR tyrosine kinase
• treats non-small cell lung cancer
• important side effects: diarrhea, vomiting, rash/dermatitis acneiform, stomatitis, paronichia, dry skin, pruritis, decreased appetite
• other side effects: Dyspnea, fatigue, pulmonary toxicity, pneumonia, sepsis
• 1 PO QDay

Question 104

Lapatinib (Tykerb)

Answer 104

• tyrosine kinase inhibitor
• mechanism: inhibits EGFR and ErbB2 (HER2) tyrosine kinase
• treats: HER2+ advanced or metastatic breast cancer; hormone+/HER2+ metastatic breast cancer in post menopausal women
• important side effects: hepatotoxicity, nausea, diarrhea, fatigue, rashes, QT-prolongation
• other side effects: decreased LV function when combined with capecitabine, hypokalemia, hypomagnesemia
• 1 PO QDay

Question 105

Ado-trastuzumab emtansine (Kadcyla)

Answer 105

• Ab-drug conjugate
• mechanism: conjugate undergoes receptor-dependent internalization & drug released inside cel
• treats: HER+ metastatic breast cancer patients with prior treatment history of trastuzumab and/or taxanel
• important side effects: fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, hypokalemia, peripheral neuropathy, ventricular dysfunction, interstitial lung disease
• other side effects: interstitial lung disease, infusion-associated reactions, hepatotoxicity, birth defects

Question 106

Panitumumab (Vectibix)

Answer 106

• fully human monoclonal antibody
• mechanism: EGFR (ErbB1)
• treats: EGFR-expressing metastatic colorectal cancers resistant to fluoropyrimidine, oxaliplatin, and irinotecan regimens
• important side effects: skin toxicities, paronychia, hypomagnesemia, fatigue, abdominal pain, nausea, diarrhea, constipation

Question 107

Nivolumab (Opdivo)

Answer 107

• human monoclona Ab
• mechanism: inhibits programmed cell death protein 1 (PD-1)
• treats: melanoma patients previously treated with ipilimumab, or those harboring the BRAF V600 mutation previously treated with ipilimumab and a BRAF inhibitor; metastatic squamous NSCLC that has progressed after platinum-based chemotherapy
• important side effects: rash, itching, cough, upper respiratory tract infections, edema, fatigue, shortness of breath, musculoskeletal pain, decreased appetite, nausea, constipation
• other side effects: severe immune-mediated side effects on healthy organs (lung, colon, liver, kidneys, hormone-producing glands