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Oncology / Chemotherapy

Oncology / Chemotherapy. NAPLEX. PG 121. What is Cancer?. Group of over 100 different diseases Characterized by uncontrolled cellular growth & proliferation Local tissue invasion Distant metastases As a group, the second-leading cause of death in Americans. PG 121. Cancer Treatments.

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Oncology / Chemotherapy

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  1. Oncology / Chemotherapy NAPLEX PG 121

  2. What is Cancer? • Group of over 100 different diseases • Characterized by uncontrolled cellular growth & proliferation • Local tissue invasion • Distant metastases • As a group, the second-leading cause of death in Americans PG 121

  3. Cancer Treatments • Surgery---local disease • Radiation---local or “regional” disease • Alpha & beta particles, neutrons penetrate cell wall • Chemotherapy- • generally for metastatic disease or suspicion/high probability of micrometastaticdx • can be used before surgery • can cure some cancers (testicular & leukemias) • Hormonal therapy- • use in prostate, breast, uterine cancers; • i.e. Prostrate – delay the progression of androgen-dependent cancer • i.e. Breast – estrogen/progesterone receptor positive tumors • Targeted therapy---most “mab”s (monoclonal antibodies) used alone or combination with chemo, targets a specific bioligic marker on the tumor or enzyme/compont • See table 2-24 and 2-25 PG 121

  4. Angiogenesis • Angiogensis – process of neovascularization – macrophages secrete angiogensis factor • Occurs from existing capillaries • Tumor cannot survive without adequate blood supply • Tumors secretes vascular endothelial growth factor (VEGF) which acts on the endothelial growth factor receptor (EGFR) to “recruit” a blood supply • MAB’s – target VEGF and EGFR • Bevacizumab (VEGF) & Cetuximab (EGFR) target PG 122

  5. Cell CycleSpecificity M (mitosis) G1 phase (Gap 1) G2 (Gap 2) S phase (DNA synthesis) • Phase-specific agents • - Most active during a particular phase • May be active during other phases • Nonphase-specific agents • - May favor a stage • Dose dependent agents SEE TABLE 2-26 PG 122

  6. Cell CycleSpecificity M (mitosis) Vinca alkaloids taxanes G1 phase (Gap 1) G2 (Gap 2) S phase (DNA synthesis) Antimetabolites 5-FU, cytarabine, methotrexate Alkylating Agents: Cisplatin Ifosfamide cyclophosphamide Hormones: Goserelin Tamoxifen Anastrozole Antibiotics: Bleomycin “rubicins” SEE TABLE 2-26 PG 122

  7. Chemo Therapy Classes • Antimetabolites - Interferes with synthesis of pyrimidine bases thus DNA synthesis • Fluorouracil • Folic Acid Analog – interferes with synthesis of pyrimidine bases thus DNA synthesis • Methotrexate • Purine Analogs – interferes with synthesis of purine bases • Fludarabine • Vinca Alkaloids – bind to tubulin to prevent formation of microtubules during mitosis • Vincristine • Podophyllotoxins – bind to tubulin – inhibiting topoisomerase II to cause DNA strand breaks • Etoposide • Taxanes – bind to tubulin – promotes synthesis of nonfunctional microtubules • Paclitaxel • Camptothecins – inhibits topiosomerase I, stabilizing single strand breaks in DNA • Topotecan • Antiandrogens – Inhibit uptake & binding of testosterone and didhydrotestosterone • Flutamide(Eulexin) • Progestins – suppresses release of luteinizing hormone and increase estrogen metabolism • Megestrol (Megace) • Antiestrogen – Bind to estrogen receptor in breast tissue – prevent binding of estrogen • Tamoxifen (Nolvadex) • Gonadotropin-releasing hormone analog – turn off negative-feedback release of FSH & LH, reduces testosterone and estrogen production • Leuprolide (Lupron)

  8. Myelosuppression Neutropenia, anemia, thrombocytopenia Nausea/vomiting cisplatin Alopecia Cyclophosphamide Mucositis Peripheral neuropathy Renal dysfunction Rash Infusion reactions Flu-like syndrome MAB’s, docetaxel Hemorrhagic Cystitis cylcophosphamide Common adverse events related to chemotherapy PG 123

  9. Common Adverse Effects Caused by Antineoplastic Drugs ** Information above is embedded in the tables p.125-130 **

  10. Common Adverse Effects Caused by Antineoplastic Drugs ** Information above is embedded in the tables p.125-130 **

  11. Which of the following medications for cancer is associated with causing cardiotoxicity? a. tamoxifen (Nolvadex) b. fluorouracil (5-FU) c. paclitaxel (Taxol) d. doxorubicin (Doxil) e. methotrexate (Rheumatrex)

  12. Which of the following medications for cancer is associated with causing cardiotoxicity? a. tamoxifen (Nolvadex) b. fluorouracil (5-FU) c. paclitaxel (Taxol) d. doxorubicin (Doxil) e. methotrexate (Rheumatrex)

  13. Drug for prevention of adverse events related to chemotherapy PG 135 – Drug Antagonist Chart

  14. Supportive Care – Nausea/Vomiting • 5HT3 inhibitors – mod/high emetogenic regimens, give one dose prechemo and sometimes oral dose for 3 days postchemo • Not for PRN use----can cause HA • Ondansetron (zofran) – inhibits 1A2, 2C9, 2D6 (weak) • Granisetron (Kytril) - less drug interactions • Dolesetron (Anzement)- QTc prolongation - 2D6 (weak) • Palonosetron (Aloxi) - subtrate 1A2, 2D6, 3A4 • NK1 (neurokinin) inhibitor - highly emetogenic regimens only- • Aprepitant (Emend) • Drug interactions – 3A4 inhibitor and inducer • Combination with 5HTs inhibitors • Benzodiazepines – anticipatory N/V • Lorazepem (Ativan) • Dexamethasone – moderately emetogenic regimens or in combo with 5HT3 for delayed N/V PG 123-124

  15. Anemia Hgb < 11 g/dL with symptoms; < 10 without symptoms EPO (Procrit) 40,000 units sq qweek Darbopoetin (Aranesp) 2.25 u/kg sq qweek Don’t forget Iron supplements Neutropenia Nadir occurs 1-2 weeks after chemo Absolute neutrophil count - ANC < 500 Filgrastim (Neupogen) 300 uq sq qd x 5-7 days Pegfilgrastim (Neulasta) 6 mg sq once 24 h post chemo Sargramostim (Leukine) 250 mcg SQ daily x 5-7 days Supportive Care PG 124

  16. Which of the following is a therapeutic substitution for ondansetron? a. Adaptin b. Kytril c. Inderal d. Seroquel e. Neurontin

  17. Which of the following is a therapeutic substitution for ondansetron? a. Adaptin b. Kytril c. Inderal d. Seroquel e. Neurontin

  18. All of the following exhibit antiemetic properties EXCEPT: a. granisetron b. loratadine c. ondansetron d. prochlorperazine e. trimethobenzamide

  19. All of the following exhibit antiemetic properties EXCEPT: a. granisetron b. loratadine c. ondansetron d. prochlorperazine e. trimethobenzamide

  20. Contraception NAPLEX PG 103

  21. Contraception • Mechanism of action: inhibit ovulation via negative feedback on the hypothalmus affecting FSH/LH release. Also alter genital tract, thicken cervical mucus. Hormonal Agents Estrogen - ethinylestradiol, mestranol Progestin - desogestrel, norgestimate, levonorgestrel, norethindrone, norgesterel Types of oral contraceptive products---various doses but estrogen dose is held constant while progestin varies Monophasic - Desogen, Yasmin, etc. Biphasic - Ortho Novum 10/11, etc. Triphasic - Triphasil, tri-Norinyl, Cyclessa, etc. Progestin only - Micronor, Ovrette, Nor-qd Extended/continuous - Seasonale PG 103

  22. Estrogens – 2 Ethinyl Estradiol (EE) Mestranol Progestins – 12 Two Possible Components Synthetic Estrogens Synthetic Progestins

  23. Contraception (cont’d) • - Treatment should be delayed one year post menarche to allow for normal cycle development • - Adverse effects of oral contraceptives Major: • Thromboembolism • Stroke • Myocardial infarction • Endometrial carcinoma • Pregnancy category X • Risk factors - Smoking - Age > 35 PG 103

  24. Contraception (cont’d) Minor: • Weight gain, edema • Breakthrough bleeding - Early BTB: Insufficient estrogen activity; associated with amenorrhea - Late BTB: Insufficient progestin activity • Nausea and vomiting • Mild depression Drug Interactions: • Antimicrobials (griseofulvin, penicillins, tetracyclines) • Enzyme inducer (barbiturates, rifampin, PIs, St.Johns Wart.) PG 104

  25. Drug Interactions with Oral Contraceptives • Anticonvulsants/Sedatives/Hypnotics: Induction of liver enzymes causes rapid metabolism of estrogen and increased binding of progestin and EE to SHBG - Sex hormone-binding globulin. • Not a problem with valproic acid or some newer anticonvulsants such as lamotrigine. • Antibiotics cause enterohepatic circulation disturbance. • Rifampin increases the metabolism of progestins.

  26. Non-Oral Hormonal Contraceptives - Medroxyprogesterone acetate injection (Depo-Provera) – q 3 mths - Estradiol cypionate and medroxyprogesterone acetate (Lunelle) - DC - Intrauterine progesterone contraceptive system (Progestasert) - Levonorgestrel intrauterine system (Mirena) – can last up to 5 years - Ortho Evra patch – apply weekly for 3 weeks, 1 week off. Less effective if > 198 lbs.-------Think about general counseling points about patches - Nuva Ring – intravaginal ring inserted for 3 weeks PG 104

  27. Contraception (cont’d) • Non-Hormonal Methods Copper interuterine devide (ParaGard) – replaced every 10 years Spermicidal foams or suppositories – do not protect from sexual transmitted diseases. Barrier methods - condoms (latex, animal membrane, male versus female); cervical cap; diaphragms Natural family planning - basal body temperature method; symptothermal method; calendar (rhythm) method PG 104

  28. Contraception (cont’d) • Abortion Pill • Mifepristone (Mifeprex-RU486)- generally used with misoprostol (Cytotec); for termination of early pregnancy (<49 days) - Increase for bacterial infections (sepsis), prolonged vaginal bleeding - Only be prescribe by physicians with a “Prescribers Agreement” - Not available in public pharmacies • Emergency Contraceptive First dose within 72 hours of unprotected sex and a second dose 12 hours later - Levonorgestrel (high dose) (Plan B) - 89% effective • Yuzpe Regimen Reduces risk of pregnancy by 75% • Lo/Ovral 30ug EE + 0.3mg norgestrel 4 now and 4 in 12 hrs PG 104

  29. Miscellaneous Hormonal Agents Ovulation stimulants • Estrogen antagonist Clomiphene citrate (Clomid, Serophene). Induces the release of FSH & LH – 6 cycles only • Gonadotropins containing FSH (recombinant DNA technology) Follitropinalfa (Gonal-F) – FSH analogs Follitropin beta (Follistim) Urofollitropin (Fertinex) • Human menopausal gonadotropins Menotropins (Pergonal, Humegon) – mixture of FSH/LH PG 105

  30. Miscellaneous Hormonal Agents (cont’d) Posterior pituitary hormones • Vasopressin (Pitressin) - antidiuretic hormone for diabetes insipidus (injection) • Lypressin (Diapid) - antidiuretic hormone for diabetes insipidus (intranasal) • Desmopressin (DDAVP) - antidiuretic hormone, used to treat primary nocturnal enuresis and diabetes insipidus (nasal spray and tablets) – also useful for hemophilia A • Oxytocin (Pitocin) - uterine stimulant – (injection) PG 105

  31. Hormones (cont’d) • Estrogens • • Conjugated estrogen (premarin, etc.) - synthetic forms : estradiol, estropipate • Estrogen dosage forms - tablet, cream, ring, transdermal patches, etc. - HRT improves lipid levels, reduces fracture risk, reduces vasomotor symptoms, DOES NOT reduce CV disease (WHI, HERS) - breast cancer risk - small, but there. Long-term use, family hx - Black Cohosh herbal has been touted for treatment of hot flashes, SSRIs, Soy product and clonidine are effective Selective estrogen receptor modulator (SERMs):raloxifene (Evista) - indicated for prevention and treatment of osteoporosis PG 106

  32. When counseling a patient about medroxyprogesterone what are the important factors to discuss? • Weight gain • Osteoporosis • Risk of pulmonary embolism a. I only b. III only c. I and II only d. II and III only e. I, II, and III

  33. When counseling a patient about medroxyprogesterone what are the important factors to discuss? • Weight gain • Osteoporosis • Risk of pulmonary embolism a. I only b. III only c. I and II only d. II and III only e. I, II, and III

  34. Osteoporosis • Low bone mass associated with age, hormone levels and medications. • DEXA • T-score >-1 is normal, -1 to -2.5 is osteopenia, and <2.5 is osteoporosis • Oral calcium and vitamin D requirement • Medications • Oral Bisphosphonates ---1 st line • Raloxifene • Calcitonin • Teriparitide • Zoledronic acid (Reclast)

  35. PG 105-106

  36. The medication Fosamax (alendronate): I. must be taken with a meal II. is used to treat hot flashes III. is available as a once weekly dose a. I only b. III only c. I and II only d. II and III only e. I, II, and III

  37. The medication Fosamax (alendronate): I. must be taken with a meal II. is used to treat hot flashes III. is available as a once weekly dose a. I only b. III only c. I and II only d. II and III only e. I, II, and III

  38. Drugs used in the prevention/treatment of osteoporosis include all of the following EXCEPT: a. Evista b. Actonel c. Calcimar d. Prempro e. Proscar

  39. Drugs used in the prevention/treatment of osteoporosis include all of the following EXCEPT: a. Evista b. Actonel c. Calcimar d. Prempro e. Proscar

  40. Which of the following is an alternative treatment for osteoporosis in patients unable to tolerate oral biphosphonates due to GI upset? I. Zoledronic Acid II. Raloxifene III. Calcium + Vitamin D a. I only b. III only c. I and II only d. II and III only e. I, II, III

  41. Which of the following is an alternative treatment for osteoporosis in patients unable to tolerate oral biphosphonates due to GI upset? I. Zoledronic Acid II. Raloxifene III. Calcium + Vitamin D a. I only b. III only c. I and II only d. II and III only e. I, II, III

  42. Which of the following products is a topical HRT? a. Evamist b. Cenestin c. Premphase d. Provera e. FemHRT

  43. Which of the following products is a topical HRT? a. Evamist b. Cenestin c. Premphase d. Provera e. FemHRT

  44. Thyroid Case Study NAPLEX Page 106 PG 106

  45. A goiter is caused by: a. hypothyroidism b. hyperthyroidism c. deficient TSH d. a thyroid tumor e. a parathyroid dysfunction

  46. A goiter is caused by: a. hypothyroidism b. hyperthyroidism c. deficient TSH d. a thyroid tumor e. a parathyroid dysfunction

  47. L-thyroxine is the same as: a. T4 b. T3 c. liothyronine d. liotrix e. cytomel

  48. L-thyroxine is the same as: a. T4 b. T3 c. liothyronine d. liotrix e. cytomel

  49. Which of the following is used as an antithyroid drug: a. methamine b. fluorouracil c. aspartame d. propylthiouracil e. protamine sulfate

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