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GER MS2 Unit 1 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

alkalating agents

A
  • produce strong electrophiles→ promote cross linking of DNA strands making them prone to breaking
  • Cell Cycle Non-Specific (CCNS)
  • side effects: carcinogenic (leukemia),bone marrow, mucosal toxicity,N/V, toxic effects on reproductive systems
  • 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
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2
Q

Mechlorethamine (Mustargen)

A
  • alkalating agent; nitrogen mustard
  • mechanism: spontaneous conversion to active metabolites in body fluids or enzymatically converted in liver
  • historically used for hodgkin’s disease, topically for treatment of cutaneous T-cell lymphoma
  • don’t use much anymore due to sterility
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3
Q

Cyclophosphamide (Cytoxan)

Ifosfaminde (Ifex)

A
  • alkalating agents; nitrogen mustard
  • produgs converted by hepatic cyt P450→ phosphoramide mustard
  • important side effects: hemorrhagic cystitis due to toxic drug metabolite acrolein (hydration and administration of MESNA minimizes problem)
  • cyclophosphamide: MC used alkylating agent (broad spectrum): ALL, CLL, non-hodgkin’s lymphoma, breast, lung, ovarian cancer
  • ifosfaminde: sarcoma and testicular cancer
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4
Q

Carmustine (Gliadel)

Lomustine (Ceenu)

A
  • alkylating agent; nitrosureas
  • brain tumors (lipophilic→ cross blood-brain barrier)
  • important side effects: renal toxicity, pulmonary fibrosis
  • other side effects: profound myelosuppression, severe N/V
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5
Q

Dacarbazine (DTIC)

Temozolomide (Temodar)

A
  • alkylating agent; triazenes
  • side effects: nausea/vomiting, myelosuppression, flu-like symptoms (fever, fatigue)
  • dacarbazine: prodrug activated by liver cytochromes; part of ABVD for Hodgkin’s disease
  • temozolomide: ​nonenzymatic conversion to methylhydrazine at physiologic pH; treats malignant gliomas
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6
Q

Cisplatin (Platinol)

A
  • alkylating agent; platinum analog (MC used)
  • doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
  • treats: testicular, ovarian, cervical, and bladder cancers
  • important side effects: nephrotoxicity, ototoxicity, peripheral motor and sensory neuropathy at high doses, severe N/V, mild to moderate myelosuppression
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7
Q

Carboplatin (Paraplatin)

A
  • alkylating agent; platinum analog
  • mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
  • treats ovarian cancer
  • side effects: myelosuppression (thrombocytopenia)
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8
Q

Oxaliplatin (Eloxatin)

A
  • alkylating agent; class: platinum analog
  • mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
  • treats: gastric and colorectal cancer
  • important: peripheral sensory neuropathy (cold-induced), neutropenia
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9
Q

Methotrexate (Trexall)

A
  • antimetabolite; folate analog (MC used)
  • inhibits DHFR (converts dietary folate to THF; needed for thymidine and purine synthesis); given orally or intrathecally (meningeal leukemia and metastases)
  • treats: childhood ALL and choriocarcinoma; combination therapy for Burkitt’s lymphoma and carcinomas of breast, ovary, head and neck, and bladder; high-dose for osteosarcoma
  • side effects: renal toxicity (crystallization in urine at high doses), hepatotoxicity (long-term, fibrosis/cirrhosis), reproductive (defective oogenesis or spermatogenesis, abortion)
  • leucovorin: prevents toxic effects of MTX (tumor cells cannot uptake folinic acid)
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10
Q

Pemetrexed (Alimta)

A
  • antimetabolite; folate analog
  • inhibits THF-dependent enzymes (e.g., DHFR, TS); metabolized to polyglutamate forms that inhibit THF-dependent enzymes (e.g., DHFR, thymidylate synthase (TS)
  • treats: mesothelioma, non-small cell lung cancer
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11
Q

5-Fluorouracil (5-FU, Carac)

A
  • antimetabolite; pyramidine analog
  • 5-FU→active metabolites: 5-FdUMP inhibits TS; inhibits DNA synthesis
  • combination therapy for breast, colorectal, gastric, head and neck, cervical and pancreatic cancer; topically for basal cell carcinoma
  • 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
  • leucovorin can potentiate effects of 5-FU
  • must be given IV (GI toxicity and rapid degradation + metabolism in gut and liver)
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12
Q

Cytarabine (AraC, Depocyt)

A
  • antimetabolite; pyramidine analog
  • Ara-C converted by deoxycytidine kinase to Ara-CMP→Ara-CTP; terminates DNA synthesis
  • treats: AML (most effective treatment), ALL and blast phase CML
  • side effects: severe myelosuppression, GI toxicity
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13
Q

Gemcitabine (dFdC, Gemzar)

A
  • antimetabolite; pyramidine analog
  • converted to active metabolites: dFdCDP inhibits ribonucleotide reductase (lowers deoxyribonucleotide); dFdCTP incorporates into DNA
  • pancreatic cancer; solid tumors (more effective than cytarabine); NSCLC, ovarian, bladder, head and neck cancer
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14
Q

antimetabolites

A
  • 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
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15
Q

6-Mercaptopurine (Purinethol)

A
  • antimetabolite; class: purine analog
  • prodrug metabolized by HGPRT→ 6-thioinosinic acid (TIMP) which inhibits de novo purine base synthesis, formation of AMP and xanthinylic acid from inosinic acid, (reducing purine levels); TIMP is converted to thio-guanine ribonucleotides inhibiting DNA and RNA synthesis
  • maintain remission in acute ALL
  • side effects: hepatotoxicity in prolonged use, BMS
  • interacts with allopurinol (inhibits xanthine oxidase), decrease 6-MP dose to avoid toxicities
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16
Q

Dactinomycin (Actinomycin D, Cosmegen)

A
  • DNA intercalating agent
  • intercalates G-C base interfering with DNA-dependant RNA pol
  • treats: pediatric tumors (Wilms’ tumor, rhabdomyosarcoma Ewing’s sarcoma); choriocarcinoma in women
  • side effects: hematopoietic suppression with pancytopenia
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17
Q

anthracycline antibiotics

A
  • DNA intercalating agents that intercalate between DNA base pairs and donate electrons to O2 → superoxide→ H2O2→ cleaved with Fe→ OH radical→ cleaves DNA
  • side effects: irreversible dose-dependent cardiotoxicity (dexrazoxane is cardio-protective)
  • daunorubicin/idarubicin: AML
  • doxorubicin: broad spectrum (sarcomas, breast, lung, malignant lymphomas)
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18
Q

Bleomycin (Blenoxane)

A
  • DNA intercalating
  • acts in G2 phase; binds to DNA, producing ss- and dsDNA breaks (mechanism similar to anthracyclines)
  • treats: combination therapy for testicular tumors or Hodgkin’s disease
  • side effects: pulmonary toxicity (pulmonary fibrosis);
  • minimally myelo- and immunosuppressive (often used in combo therapy)
  • dexrazoxane is cardio-protective
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19
Q

Vinca Alkaloids

A
  • MT inhibitors that blocks tubulin polymerization into MTs
  • resistance
  • vinblastine: treats metastatic testicular tumors (+ bleomycin, cisplatin); component of ABVD for Hodgkin’s disease; BMS
  • vincristine: treats childhood AL (+ glucocorticoids); dose-limiting neurotoxicity (peripheral neuropathy); low BMS
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20
Q

taxanes

A
  • MT inhibitors that block MT depolymerization into tubulin
  • treats: metastatic breast, ovarian, lung, and head and neck cancers
  • side effects: peripheral neuropathy, neutropenia, hypersensitivity reactions
  • paclitaxel: metastatic breast, ovarian, lung, head, neck
  • docetaxel: hormone refractory prostate cancer
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21
Q

epipodophyllotoxinss

A
  • inhibits topoisomerase II (breaks and reseals dsDNA)
  • side effects: dose-limiting myelosuppression (neutropenia), oral mucositis
  • etoposide: broad spectrum (testicular carcinoma, lung cancer, non-Hodgin’s lymphoma)
  • teniposide: ALL
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22
Q

camptothecin analogs

A
  • inhibits topoisomerase I (breaks and reseals ssDNA)
  • side effects: severe neutropenia, severe diarrhea
  • irinotecan: advanced colorectal cancer
  • topotecan: ovarian and SCLC
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23
Q

hormone therapy

A
  • used in the treatment of hormone-dependent neoplasms
  • classes: glucocorticoids, SERMs, SERDs, aromatase inhibitors, GnRH blockers, nonsteroidal androgen receptor blockers
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24
Q

glucocorticoids

A
  • hormone therapy; inhibit mitosis in lymphocytes
  • prednisone: ALL (+ vincristine)
  • dexamethasone: reduces edema in brain and spinal cord tumors with radiation therapy
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25
Q

Tamoxifen (Soltamox)

A
  • hormone therapy; SERM (competes with estradiol for binding to ER)
  • treats: ER+ breast cancer and prevention of breast cancer in high-risk patients
  • side effects: hot flushes, hair loss; increased risk of endometrial cancer (weak agonist of ER in endometrium); increased risk of thromboembolic events
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26
Q

Fulvestrant (Faslodex)

A
  • hormone therapy; class: SERD
  • binds with much higher affinity (>100-fold) to ER vs. tamoxifen, inhibiting dimerization, increasing degradation, and reducing overall ER levels
  • treats: posmenopausal women with ER+ metastatic breast cancer
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27
Q

aromatase inhibitors

A
  • hormone therapy; class: aromatase inhibitor
  • ER + breast cancer in postmenopausal women
  • aminoglutethamide: relatively weak, significant side effects (no longer used)
  • anastrazole/letrozole: nonsteroidal AI
  • exemestane: steroidal AI
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28
Q

hormone therapy for prostate cancer

A
  • androgen ablation therapy of GnRH analog + AR blocker
  • leuprolide: GnRH analog (binds GnRH receptor inhibiting FSH and LH but does not inhibit adrenal androgen synthesis)
  • flutamide/bicalutamide: nonsteroidal AR blockers competes with AR for binding
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29
Q

Imatinib (Gleevac)

A
  • tyrosine kinase inhibitor; prevents phosphorylation of Abl-kinase substrate; metabolized by cyt P450
  • first line therapy for CML
  • side effects: N/V, BMS
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30
Q

Gefitinib (Iressa)

Erlotinib (Tarceva)

Afatinib (Gilotrif)

A
  • inhibits EGFR tyrosine kinase
  • treats: non-small cell lung cancer
  • side effects: poddibility of bleeding, interstitial lung disease
  • metabolized by CYP3A4 (ketoconazole interacts); PPIs reduce absorption
  • afatinib: pulmonary toxicity
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31
Q

Rituximab (Rituxan)

A
  • chimeric monoclonal antibody; CD20 B-cell antibody that directly activates apoptosis, complement, or cell-mediated cytotoxicity (e.g., T cells, NK cells)
  • treats: non-Hodgkin’s lymphomas
  • important side effects: infusion reactions, tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML)
  • patients need careful monitoring
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32
Q

Trastuzumab (Herceptin)

A
  • monoclonal antibody; unknown HER2/neu (ErbB2) receptor antibody mechanism (enhanced receptor endocytosis or blocking homo- or heterodimerization)
  • treats: HER2/neu-overexpressing metastatic breast cancer
  • side effects: hypersentivity reaction, ventricular dysfunction, cardiomyopathy, CHF, infusion reactions→ pulmonary toxicity
  • usually combined with taxanes; enhances doxorubicin cardiotoxicity
33
Q

Cetuximab (Erbitux)

A
  • monoclonal antibody that binds to EGFR1 (ErbB1) with similar affinity as EGF or TGF-a
  • treats: EGFR+ metastatic colorectal cancer
34
Q

Ipilimumab (Yervoy)

A
  • human monoclonal antibody
  • mechanism: Cytotoxic T-Lymphocyte Antigen 4 inhibitor; stimulates immune system
  • treats: melanoma
35
Q

Hydroxyurea (Hydrea)

A
  • inhibits ribonucleoside diphosphate reductase (catalyzes ribonucleotides to deoxyribonucleotides)
  • treats: myeloproliferative neoplasms, sickle cell disease (increases Hb-F)
36
Q

Retinoids

A
  • all trans retanoic acid (ATRA) induces terminal differentiation in malignant immature promyelocytes, which subsequently apoptose
  • treats: APL
37
Q

Arsenic Trioxide (Trisenox)

A

heavy metal toxin that treats relapsed APL

38
Q

Thalidomide (Thalomid)

A

treats multiple myeloma and myelodysplastic syndromes

39
Q

Interferons

A

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

40
Q

ABVD

A

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

41
Q

CHOP

A

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

42
Q

MOPP

A

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

43
Q

CMF

A

combination therapy of cyclophosphamide, methotrexate, 5-fluorouracil

44
Q

FEC

A

combination therapy of 5-fluorouracil, epirubicin, cyclophosphamide

45
Q

Diethylstilbestrol (DES)

A
  • non-steroidal synthetic estrogen
  • increased risk of clear cell adenocarcinoma of vagina & cervix
46
Q

Tamoxifen citrate (Nolvadex)

A
  • non-steroidal anti-estrogen; selective estrogen receptor modifier
  • ER competitive antagonist (use in high doses because estrogen has much higher binding affinity)
  • anti-estrogenic effect on mammary epithelium (treats ER+ breast cancer)
  • pro-estrogenic effect on uterine epithelium (increase risk of endometrial cancer), bone, and endometrium
47
Q

Clomiphene citrate (Clomid)

A
  • non-steroidal anti-estrogen
  • ER competative antagonist in hypothalamus (no estradiol negative feedback)→ increased secretion of FSH/LH→ ovulation
  • trans-isomer is a potent estrogen antagonist (dominant isoform), cis-isomer is a weak estrogen agonist
48
Q

Levonorgestrel (Plan B)

A
  • 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
49
Q

Mifepristone (RU-486, Korlym)

A
  • anti-progestin; glucocorticoid receptor antagonist
  • competitively binds to PR (leading to detachment of fetus); glucocorticoid receptor antagonist
  • “the abortion pill”, also sed for cushing’s syndrome
  • must take early (by day 49)
  • PO but must be given in medical facility (surgery if abortion incomplete)
50
Q

erectile dysfunction drugs

A
  • PDE5 inhibitors (inhibits PDE5 breakdown of cGMP→ decreased Ca→ smooth muscle relaxation→ erection)
    • sildenafil citrate, verdenafil* HCl, tada_lafil_*
  • improves response to sexual stimulation (does not trigger erection)
  • important side effects: headache, dizziness, change in vision (NAION due to sudden decreased blood flow to optic nerve)
  • PO (once/day max)
  • contraindicated if on nitrates or α-blockers (unsafe drop in BP)
51
Q

Indomethacin (Indocin)

Naproxen (Aleve)

A
  • non-selective NSAID used as symptomatic treatment of RA and acute gouty arthritis
  • eliminate pains and reduces inflammation but does not slow RA disease progression
  • side effects: ​gastric and duodenal ulcers
52
Q

COX-2 inhibitors

A

selective NSAID that is superceding conventional NSAIDs for symptomatic treatment of RA due to reduced side effects (​50% fewer gastric and duodenal ulcers)

53
Q

glucocorticoids (corticosteroids)

A
  • DMARD for RA and acute gouty arthritis
  • inhibits phospholipase A2 (inhibiting release of arachidonic acid and formation of prostaglandins) and inhibits cytokine production (prevents induction of COX-2)
  • given orally or intraarticular injection; not for long term use
  • started initially (fast acting) before other drugs become effective
54
Q

Methotrexate (Trexall) for RA

A
  • DMARD (immunosuppressive)
  • gold standard for RA; low dose used (vs. cancer treatment; hepatotoxicity is rare)
  • inhibition of AICAR transformylase and thymidylate synthetase which effects PMN chemotaxis; causes adenosine accumulation (inhibits inflammation)
  • takes several weeks to start working
55
Q

Colchicine (Colcrys)

A
  • treats acute gouty arthritis
  • prevents tubulin polymerization→ inibition of leukocyte migration, phagocytosis, and release of cytokines
  • small therapeutic window; N/V/D, long-term use causes peripheral neuropathy & neutropenia
  • works in 12-24 hours
56
Q

Probenecid (Benemid)

A
  • treats chronic tophaceous gout
  • uricosuric agent (competes with urate at anionic transport site of renal tubule to inhibit urate reabsorption→ increased rate of urate excretion, decreased plasma levels)
  • decreased secretion of some weak acids (e.g., penicillin)
  • urate crystal mobilization can lead to acute gouty arthritis; GI irritation
57
Q

Allopurinol (Zyloprim)

A
  • treats chronic tophaceous gout
  • reduces uric acid synthesis by inhibiting xanthine oxidase (competitive inhibition)→ alloxanthine (non-competitive inhibitor of xanthine oxidase)
  • mobilization of urate crystals can leads to acute gouty arthritis
58
Q

Pegloticase (Krystexxa)

A
  • recombinant, stabilized uricase
  • mechanism: converts uric acid to allantoin
  • treats: chronic tophaceous gout
59
Q

Ado-trastuzumab emtansine (Kadcyla)

A
  • Ab-drug conjugate: trastuzumab + DMI (MT inhibitor)
  • mechanism: conjugate undergoes receptor-dependent internalization & drug released inside cell
  • treats: HER+ metastatic breast cancer patients with prior treatment history of trastuzumab and/or taxane
  • side effects: ventricular dysfunction, hepatotoxicity
60
Q

Panitumumab (Vectibix)

A
  • fully human monoclonal antibody EGFR (ErbB1)
  • treats: EGFR-expressing metastatic colorectal cancers resistant to fluoropyrimidine, oxaliplatin, and irinotecan regimens
  • side effects: skin toxicities
61
Q

Rheumatoid Arthritis

A
  • chronic, inflammatory autoimmune disease
  • MC systemic inflammatory disease
  • activated macrophages→ TNF-a and IL-1→ activate synovial fibroblasts→ recruitment of other inflammatory cells→ release of metalloproteinases→ bone and cartilage degradation
  • nonbiologic DMARD in early RA with low disease to prevent progression
  • patients with high disease and poor prognostic features may be started on anti-TNF therapy w/or w/out methotrexate
62
Q

DMARDs

A
  • disease modifying anti-rheumatic drugs
  • quinolones: historically used, less efficacious than other DMARDs
  • glucocorticoids (corticosteroids)
  • sulfasalazine: used in europe
  • methotrexate: gold standard immunosuppressive DMARD
  • leflunomide: newer immunosuppressive DMARD prescribed if patient is becoming insensitive to methotrexate
63
Q

biological response modifiers for treatment of RA

A
  • highly specific therapeutics to target cytokines and surface molecules
  • TNF as target: Etanercept, Infliximab, Adalimumab, Golimumab, Certolizumab
  • IL-1 as target: Anakinra
  • IL-6 as target: Tocilizumab
  • T-cell as target: Abatacept
  • B-cell as target: Rituximab
  • JAK as target: Tofacitinib
64
Q

gout

A

acute, often recurrent arthritis mediated by crystallization of uric acid within joints, typically associated with hyperuricemia

65
Q

therapeutic strategies for gout

A
  • acute gouty arthritis: deposits of uric acid in joint, pain subsides after a few days if untreatment; affects big toe (podagra)
    • NSAIDs and lifestyle changes/drug alteration
    • colchicine
    • corticosteroids​ (if NSAIDs, corticosteroids contraindicated)
  • chronic tophaceous gout: deposits of urate (tophi) in tissues that persist and cause destruction
    • lifestyle changes/drug alteration
    • ​uricosuric agent: probenecid
    • reduce uric acid synthesis: allopurinol, febuxostat
66
Q

synthetic estrogens

A
  • absorbed through skin, mucous membranes, GI tract and widely distributed
  • used for contraception, primary hypogonadism, postmenopausal hormone therapy, prevention of osteoporosis
  • contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeding, prenancy, thromboembolic disease, HTN, hepatic disease, FH of breast or uterine cancer
  • steroidal:
    • ​estradiol esters: estradiol valerate/ cypionate
    • conjugated estrogens: estrone/ equilin sulfate
    • alkyl estrogens: ethinyl estradiol, mestranol
  • nonsteroidal: less commonly used (e.g., DES)
67
Q

progestins

A
  • used for contraception, hormone replacement therapy (counter endometrial stimulator effects of estrogen)
    • suppresses LH secretion preventing ovulation, thickens cervical mucus, develops endometrial atrophy
  • contraindicated in thromboembolic disorders, liver disease/dysfunction, undiagnosed vaginal bleeding, pregnancy
  • natural: minimal side effects
    • micronized and transvaginal progesterone
  • synthetic: strong androgenic activity
    • medroxyprogesterone, norethindrone, norgestrel, megestrol
68
Q

contraceptive types

A
  • estrogen-progestin combination: most effective, estrogenic and progestin effects
    • mono/bi/triphasic orthonovum (fixed estrogen, progestin increases in phases)
  • progestin-only: less effective than combination preparations, useful when estrogens are contraindicated; irregular menstrual cycle
    • minipill
  • post-coital: take within 72 hours of coitus
    • levonorgestrel (plan B)
69
Q

clonal evolution vs. cancer stem cell theory

A
  • clonal evolution: all tumors arise from a single transformed clone; new subclones differ from original clone (e.g., become more aggressive, metastatic, and acquire ability to evade host defenses)
  • cancer stem cells: sub-population of cells with ability to self-renew and differentiate; have cancer initiating potential
  • important because conventional therapy targets differentiated cells NOT stem cells so there remains the ability for the tumor to regrow
70
Q

stages of cell cycle

A
  • G1: cell growth before DNA duplication; Cdk4-cyclinD
  • S: DNA synthesis; Cdk2-cyclinA
  • G2: preparation for division; Cdk1-cyclinB
  • M: mitosis; Cdk1-cyclinB
  • G0: postmitotic cells exit cycle and enter into non-proliferative phase
71
Q

resistance to anticancer drugs

A
  • intrinsic: dysregulation of one or both apoptotic pathways; hyperactivity of survival or antiapoptotit genes/proteins; host factors
  • aquired: dysregulation of one/bone apoptotic pathways during chemotherapy; aquired ability to rapidly and efficient repair DNA damage; gene amplification; increased expression of energy-dependent efflux pumps (p-glycoprotein); decrease drug uptake because transporters stop working; dysregulation in drug metabolism
72
Q

log kill hypothesis

A

chemotherapeutic agents follow 1st order kinetics (a given dose of drug kills a constant fraction of cancer cells rather than a constant number of cells)

  • give chemotherapy based on body weight
73
Q

verapamil

A

Ca2+ channel blocker that inhibits p-glycoprotein (efflux transporter in gut that pumps drugs back into the lumen, decreasing their absorption)

74
Q

stages of drug development

A
  • preclinical study
  • investigational new drug application
  • phase I: determine safe and appropriate dose
  • phase II: determine effectiveness and side effects
  • phase III: effectiveness of new drug vs. standard of care
  • new drug application
  • FDA approval
  • phase IV: long-term safety and effectiveness
75
Q

CML and treatment

A
  • clonal hematopoietic stem cell disorder
  • presence of Ph in more thant 90%; t(9:22) fuses BCR with ABL→constituitely active tyrosine kinase
  • treat with tyrosine kinase inhibitors:
    • imatinib (gleevac): prevents phosphorylation of substrate
    • nilotinib/dasatinib/bosutinib: imatinib resistant CML
    • ponatinib: prior CML therapy resistance and patients with T315I mutation
76
Q

melanoma and treatment

A
  • BRAF genes in 45-50 of cutaneous melanomas, more common in those associated with sun-induced damage
  • use the following drugs for unresectable stage III and IV or BRAF+ metastatic melanomas; do not give to melanomas with wt BRAF
  • vemurafenib: inhibits BRAF kinase; long QT and SCC
  • dabrafenib: inhibits BRAF kinase; serious febrile drug reactions, higher risk of developing cutaneous SCC
  • trametinib: inhibits MEK (downstream of BRAF); serious skin toxicities
77
Q

CYP enzymes

A
  • major enzymes inolved in drug metabolism; perform phase 1 redox reactions
    • have central heme that moves electrons
  • interact with >250 drugs
    • known inducers: smoking, st. john’s wart
    • known inhibitors: grapefruit juice, macrolides
78
Q

CYP polymorphism

A
  • based on number of functional alleles
  • 2C9 (warfarin): 1-3% are poor metabolizers
  • 2C19 (clopidogrel, diazepam): 20% AAs and asians are poor metabolizers
    • has the most common loss of function alleles in the US
  • 2D6 (codeine, psych): 5-10% whites are poor metabolizers; 30% ethiopians are ultra metabolizers

GER MS2 Unit 1 (3 decks)

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