Term
2005 Estimated US Cancer Rates
(Dr. Horner) |
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Definition
| Men: Prostate 33%, Lung 13%, Colon and rectum 10%, Urinary bladder 7%; Women: Breast 32%, lung and bronchus 12%, Colon and rectum 11%, uterine corpus 6% |
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Term
2005 Estimated US Cancer Deaths
(Dr. Horner) |
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Definition
| Men: Lung 31%, Prostate 10%, Colon 10% pancreas 5%; Women: lung 27%, breast 15%, colon 10%, ovary 6% |
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Term
Cancer Emergence
(Dr. Horner) |
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Definition
| consequence of step-wise accumulation of genetic defects; vary form tumor-type to tumor-type and patient-patient |
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Term
Problems with Cancer Chemotherapy:
Drug Resistance
(Dr. Horner) |
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Definition
| increased expression of MDR gene/P170; downregulation of activating enzymes;upregulation of catabolic enzymes;mutation of target receptors and enzymes;constitutive inhibition of apoptosis |
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Term
Major Toxicities of Chemotherapeutic Drugs
(Dr. Horner) |
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Definition
| bone marrow suppression: neutropenia, thrombocytopenia, anemia; digestive tract injury, N/V; alopecia; reproductive toxicity; hyperuricemia;local tissue injury via vecicants; carcinogenesis, unique toxicities, dose-limiting toxicities |
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Term
Anticancer Drug Classification
(Dr. Horner) |
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Definition
Cytotoxic drugs: action on DNA- alkylating agents, platinum compounds, antitumor antibiotics, antimetabolites, topoisomerase inhibitors; action on mitotic spindle- microtubule inhibitors
Targeted therapies: hormones and hormone modulators- hormones, modulotors of hormone release and action; receptor and intracellular signalling- growth signal pathway inhibitors, angiogenesis inhibitors |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
hormonal therapy; SERM, selctive estrogen receptor modulator used for breast cancer treatment; metab/excr: highly protein bound/hepatic
MOA: cpmpetitive inhibitor of ER, leading to defective signal transduction and transcription; stimulates secretion of TGF-beta |
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Term
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Definition
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Term
Alkylating agent MOA
(Dr. Horner) |
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Definition
| prodrugs converted in vivo to active metabolites by enzymatic (P450) or spontaneous conversion, conversion= active alkylating form of drug+leaving group, action-covalent bonding via alkyl group of the drug to the nucleophilic group DNA, DNA sites that are prone to alkylation- N7-Guanine, N1&N3-adenine, N3-cytosine, others |
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Term
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Definition
| allows apoptosis to become active |
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Term
| Epidermal growth factor receptor |
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Definition
| EGFR 1 and 2, control proliferation and angiogenesis |
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Term
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Definition
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Term
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Definition
| Platinum drug; tx: testicular CA |
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Term
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Definition
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Term
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Definition
| covalent binding to DNA resulting in cross-linked strands that inhibit synthesis and transcription |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
Platinum Drug toxicities
(Dr. Horner) |
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Definition
| metabolized and excreted by kidney- nephrotoxicity (cisplatin), neurotoxicity (cis and oxali), severe N/V (especially cisplatin, ondansetron 5HT3 antagonist), myelosupression (carb, oxali), carboplatin has less nephrotoxicity, neurotoxicity and severe nausea |
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Term
| Therapeutic consideration for cisplatin |
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Definition
| prevention cis-indused nephrotoxicity with chloride diuresis and amifostine (cycloprotective agent) |
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Term
| Therapeutic consideration for carboplatin |
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Definition
| creatinine clearance <60 ml/min needs dosage adjustment |
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Term
Alkylating Agents: cause of cell death
(Dr. Horner) |
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Definition
DNA cross-linking: miscoding of DNA; base excision and DNA strand breakage
Apoptosis- the p53 gene senses DNA damage and initiates apoptosis in response to DNA alkylation
Outcome: DNA synthesis and cell division disrupted |
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Term
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Definition
| Intercalation of DNA- inhibits DNA synthesis; Inhibition of topoisomerase II- DNA strand breaks; cell membrane altered- fluidity and ion transport; free radical formation- generation of semiquinone free radicals and oxygen free radicals |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| Anthracycline metabolism/excretion |
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Definition
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Term
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Definition
| myelosuppression, CHF- dose dependant, alopecia, vesicant |
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Term
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Definition
| highly reactive chemicals that combine with proteins, DNA, and other cellular components to result in cellular changes immediately after exposure. |
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Term
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Definition
| cardiotoxicity, irreversible, cumulative & dose-dependent; acute- arrhythmias (sinus tachycardia), long term- cardiomyopathy with CHF; dexrazoxane= antidote= iron chelator |
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Term
Microtubule inhibitors
(Dr. Horner) |
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Definition
Taxanes: Paclitaxel, Docetaxel
Vinca alkaloids: Vinblastine, Vinorelbine, Vincristine |
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Term
| Microtubule inhibitors MOA |
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Definition
Vinca alkaloids- (Vinblastine, Vincristine) bind to tubulin and block tubulin polymerization-> dissolution mitotic spindle
Taxanes- (Paclitaxel) bind to tubulin and prevent depolymerization-> continued polymerization= highly stable but dysfunctional microtubules |
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Term
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Definition
Paclitaxel and Docetaxel
MOA: high affinity microtubule binding/inhibition of mitotic spindle function
Metab./Excer: hepatic |
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Term
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Definition
| myelosuppression, alopecia, neurotoxicity (P), hypersensitivity Rxn (P>D), fluid retention (D) |
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Term
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Definition
| all stages of breast cancer, non small cell lung cancer, ovarian cancer, bladder cancer |
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Term
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Definition
prototypes: Vincristine, Vinorelbine
MOA: inhibits tubulin polymerization, disrupting mitotic spindle formation
Metab/Excer: liver metab (P450), biliary excretion. |
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Term
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Definition
| peripheral neuropathy (Vcr), myelosuppression (Vino), vesicant |
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Term
| Vinca alkaloids clinical use |
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Definition
| non-hodgkin lymphoma (Vcr), Hodgkin lymphoma (Vlb), Breast cancer (Vnr), non small cell lung cancer (Vnr) |
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Term
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Definition
| compound that mimic the structure of folic acid, pyrimidines or purines, interrupting DNA/RNA synthesis and function |
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Term
| Antimetabolite prototype drug |
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Definition
| Methotrexate (MTX) now rarely used |
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Term
| Fluorouracil/Capecitabine MOA |
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Definition
inhibition of thymidylate synthase by metabolite FdUMP, metabolites incorporate dinto DNA/RNA, cell-cycle specific
Capecitabine an oral FU prodrug, activated in tumor cells by thymidine phosphorylase |
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Term
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Definition
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Term
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Definition
| structurally imitate purines, incorporated into DNA and RNA and prompty lead to death of cell |
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Term
| Fluorouracil/Capecitabine Toxicities |
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Definition
| myelosupression, mucositis/diarrhea, hand foot syndrome |
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Term
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Definition
| menopausal symptoms, endometrial cancer, DVT |
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Term
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Definition
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Term
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Definition
| inhibition of aromatase, eliminating 95-98% post-menopausal estrogen production |
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Term
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Definition
| antimetabolite. Major SE: mucositis, diarrhea, hand-foot syndrome and flu-like symptoms. |
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Term
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Definition
| topoisonmerase inhibitor. Major SE: acute and chronic diarrhea. |
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Term
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Definition
| taxane. Major SE: allergic hypersensitivity reactions, neurotoxicity and fluid retention. |
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Term
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Definition
| LHRH agonist. used in metastatic prostate CA. suppresses FSH and LH secretion by the pituitary resulting in "chemical castration" no longer do orchidectomy. |
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Term
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Definition
| LHRH agonist. used in metastatic prostate CA. suppresses FSH and LH secretion by the pituitary resulting in "chemical castration" no longer do orchidectomy. |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| antiemetic. steroid often combined with a selective serotonin 5-HT3 receptor antagonist such as granisetron or ondansetron (Zofran) to prevent or reduce chemotherapy-induced N/V. blocks receptors in the GI tract and vomiting centers in the medulla. |
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Term
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Definition
| Selective serotonin 5-HT3 receptor antagonist. Combined with steroid Dexamethasone to prevent or reduce chemo-induced N/V. |
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Term
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Definition
| Selective serotonin 5-HT3 receptor antagonist. Combined with steroid Dexamethasone to prevent or reduce chemo-induced N/V. |
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Term
| Hematological support of chemotherapy. |
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Definition
| erythropoietin. filgrastim, pegfilgrastin |
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Term
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Definition
| long-acting hematological support, given once per chemoRx cycle. |
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Term
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Definition
| long-acting hematological support, given once per chemoRx cycle. |
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Term
| Normal absorption and distribution of iron (Dr. Reese) |
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Definition
| dietary or therapeutic iron is usually absorbed in the duodenum, proximal jejenum and distal small bowel. Absorbed in the ferrous form (2+) and transported across the intestinal mucosal cell by active transport. Iron (ferric form) is transported in plasma bound to transferrin to liver, spleen or marrow. |
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Term
| Factors involved in iron absorption (Dr. Reese) |
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Definition
| If stores of Fe are high and requirements are low, newly absorbed iro is diverted to ferritin, if stores are low and requirements high, newly absorbed iron is immediately transported form the mucosal cells to the bone marrow for production of Hb. Gastric resections decreased Fe absorption- decrease HCl production, decreased digestion of dietary Fe |
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Term
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Definition
| Iron is stored in macrophage: ferritin: since plasma ferritin is in equilibrium with stoarge ferritin in the RE system, plasma serum ferritin levels can be used to estimate total body stoers. Hemosiderin- aggregates of Ferric core crystals. |
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Term
| safest and least expensive iron deficiency treatment (Dr. Reese) |
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Definition
| Oral route. usual prep: ferrous sulfate but can use ferrous gluconate or ferrous fumarate. maximal absorption in fasting state (1hr before or 2hrs after meal) absorption enhanced by OJ but inhibited by tea and milk. |
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Term
| Iron therapy in children (Dr. Reese) |
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Definition
| effective dosage is 1.5 to 2mg elemental iron per kg three times per day if tolerated. Use elixirs or syrups. |
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Term
| Side effects of oral iron (Dr. Reese) |
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Definition
| GI symptoms; heartburn, nausea, cramps, diarrhea. usually dose related. warn patients that stools may turn black. Iron toxicity. |
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Term
| Acute iron toxicity (Dr. Reese) |
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Definition
| may cause necrotizing gastroenteritis, vomiting, abdominal pin and bloody diarrhea followed by shock, lethargy and dyspnea. May progress to metabolic acidosis, coma and death. Store iron tablets carefully. |
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Term
| Parenteral iron therapy (Dr. Reese) |
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Definition
| seldom indicated in general practice, used in dialysis pateints, concern with uncommon systemic immediate allergic reactions, suggest consult before use. |
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Term
| Preventive Iron therapy in high risk groups (Dr. Reese) |
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Definition
| infants, pregnant women, regular blood donors, women with menorrhagia. |
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Term
| Folate therapy (Dr. Reese) |
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Definition
| the ultimate role of folate is the formation of folate cofactors essential for one-carbon transfer reactions necessary for DNA synthesis. deficiency--> megaloblastic anemia (high MCV) |
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Term
| Folate deficiency causes (Dr. Reese) |
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Definition
| poor diet (rich sources: leafy green vegetables, yeast and animal protein) alcoholics, fad dieters. Drugs: pheytoin, oral contraceptives and INH may interfere with absorption, Trimethoprim and MTX may interefere with metabolism of folate, but less likely to cause anemia. |
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Term
| Folate therapy route/dosage (Dr. Reese) |
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Definition
| well absorbed even in those with malabsorption syndromes. 1mg/day in adults, preventive therapy in high risk patients (pregnany women, alcoholics, ongoing hemolytic anemias) 0.4mg. IV formulations rarely used unless pt is NPO. |
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Term
| Vitamin B12, cobalamine, deficiency (Dr. Reese) |
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Definition
| arise from poor dietary intake (vegan), defective secretion of IF (pernicious anemia, gastrectomy), poor absorption at distal ileum if diseased (inflammatory bowel disease) or removed surgically. |
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Term
| Enzymatic reactions affected by B12 deficiency. (Dr. Reese) |
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Definition
| folate metabolism and DNA synthesis. formation of succinyl CoA-> abnormal fatty acids, which when incorporated into cell membranes of the CNA may explain CNA abnormalilties of B12 deficiency. |
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Term
| B12 deficiency Replacement therapy (Dr. Reese) |
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Definition
| usually parenteral since malabsoprtion is a common cause. two parenteral IM perps are avialable (cyancobalamin or hydroxycobalamin) |
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Term
| Cyanocobalamin and hydroxycobalamin |
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Definition
| IM parenteral preps of B12 replacement therapy. |
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Term
| Older patient iron deficiency |
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Definition
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Term
| erythropoietin biological role (Dr. Reese) |
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Definition
| glycoprotein normally made mostly in the kidney, small amount in the liver. stimulates erythroid proliferation and differentiation by interacting with specific erythopoietin receptors on erythroid cells in the marrow. |
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Term
| erythropoietin production in anemia (Dr. Reese) |
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Definition
| kidney noramlly produces more to stimulate RBC formation. (Normal levels <20IU/L. In anemia normally levels >100-400IU/L) In chronic renal disease, levels are low since kidney cannot produce erythropoietin. |
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Term
| Erythropoietin therapy indications (Dr. Reese) |
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Definition
| chronic renal failure, cancer, cancer chemotherapy, HIV infection, also for reduction of blood transfusions for certain types of elective surgery in anemia patients, long term ICU patients are being studied. Exclude Fe deciency. |
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Term
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Definition
| recombinant formation of erythropoietin. Given SQ or IV usually 2-3 times per week. starting dose 50-100u/kg TIW but lower doses may work and clinicians tirate its use. see clinical response in 2-6-8 weeks, expensive $9/1000units. |
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Term
| Erythropoietin therapy SE (Dr. Reese) |
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Definition
| rare allergic reactions, hypertension, HA, edema, local skin reactions, uncommon seizures, thrombotic events. |
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Term
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Definition
| long acting erythropoietin, approved in late 2001, T1/2 is 2-3 times longer than epoetin, only give once weekly, as effective as epoetin in renal failure. |
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Term
| Hydroxyurea in sickle cell anemia (Dr. Reese) |
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Definition
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Term
| RBC transfusion risks (Dr. Reese) |
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Definition
| fatal hemolytic reaction (1/500,000), HIV (1/500,000), HCV (1/100,000), HBV (1/63,000), volume overload, bacterial contamination, wrong unit given, nonspecific immunosuppresion |
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Term
| Blood bank stores considerations (Dr. Reese) |
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Definition
| Will bank blood stored typically >20days do what we think/hope it will? decreased levels of 2,3 DPG, RBC become deformed |
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Term
| Heparin types (Dr. Reese) |
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Definition
| unfractionated, low molecular weight |
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Term
| Unfractionated Heparin (Dr. Reese) |
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Definition
| from either bovine lung or porcine intestinal mucosa sources. Introduced into clinical medicine in the 1940s. Heterogenous product. Mean MW= 15,000. |
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Term
| Low Molecular Weight Heparin (Dr. Reese) |
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Definition
| manufacture from unfractionated heparin by controlled depolymerization or enzymatic techniques. MW= 4000-6000. |
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Term
| Unfractionated standard heparin (Dr. Reese) |
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Definition
| anticoagulant. not absorbed after oral administration. must be given by injection, usually IV, SQ especially for prophylaxis. Continuous infusions preferred. Heparin is highly negative charged, can bind to a variety of plasma proteins, proteins secreted by platelets and endothelial cells. dosing is individualized. |
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Term
| Heparin metabolism (Dr. Reese) |
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Definition
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Term
| Heparin therapy monitoring (Dr. Reese) |
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Definition
| serial activated partial thromboplastin times (aPTT). sensitive to teh inhibiting affects of heparin on thrombin, Xa and IXa. sometimes monitored by measuring antifactor Xa. |
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Term
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Definition
| LMWH, MOA: inhibits only Xa, give SQ once daily, long T1/2 about 18 hrs, may caused prolonged effect; not reversed with protamine. renal excretion: unclear how to dose in renal failure. does not seem to cause HIT, does not cross placenta: can use in pregnancy. more cost effective than enoxaparin (Levenox) in preventing DVT |
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Term
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Definition
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Term
| Pharmacology of LMWH (Dr. Reese) |
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Definition
| less protein bound; less binding to endothelium; less platelet interaction. Excellent bioavailability, more predictable response, fixed dosing QD or BID, no monitoring so far less thrombocytopenia. |
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Term
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Definition
| inhibits factor Xa more than trombin. |
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Term
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Definition
| vitamin K epoxide reductase is the warfarin-sensitive step; 100% bioavailability; food may delay absorption; crosses placenta can cause hemorrhagic disorder in fetus; metabolized into inactive compounds- excreted in urine and stool; many drug-drug interactions. |
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Term
| Pharmacokinetics and dynamics of warfarin interactions (Dr. Reese) |
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Definition
| synergism, reduced clotting factors in liver disease patients; aspirin- will inhibit platelet function, increasing risk of bleeding; enzyme induction or inhibition and reduced absorption; TMP-SMZ will increase protime by inhibiting warfarin metabolism; Cholestyramine reduces absorption of warfarin. |
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Term
| Complications and contraindications of warfarin treatment (Dr. Reese) |
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Definition
| bleeding, skin necrosis (rare), fetal effects. CI: active bleeding, pt noncompliance, recent CNS or eye surgery, significant liver disease, melanoma in the CNS. |
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Term
| Bacterial meningitis differential from viral (Dr. Reese) |
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Definition
| sicker patients; faster pace of disease; CSF with poly predominance and decrease lucose; increase peripheral WBC and left shift; CSF culture will indicate pathogen (if not on antibiotics) |
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Term
| Viral meningitis differential from bacterial (Dr. Reese) |
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Definition
| patients usually not as ill; CSF with lymphocytic predominance and normal glucose; aspetic formula; PCR helps ID enteroviruses. |
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Term
| When do you do an LP? (Dr. Reese) |
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Definition
| acute presentation with fever, new HA, toxic; subacute HA and fever |
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Term
| Contraindications to LP (Dr. Reese) |
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Definition
| suspect mass lesion or increased intracranial pressure; coagulopathy; severe scoliosis or infected lumbar area |
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Term
| Likely pathogens for adult meningitis (Dr. Reese) |
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Definition
| S. pneumoniae, N. meningitidis. Less likely H flu b. In immunocompromised or eldery: L. monocytogenes |
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Term
| likely pathogens in child meningitis (Dr. Reese) |
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Definition
| S. pneumo, N. menigitidis. depending on vaccination Hx: H. flu |
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Term
| likely pathogens for neonate meningitis (Dr. Reese) |
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Definition
| Strep agalactiae (GBS), gram neg. bacilli: E. coli, Klebsiella |
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Term
| Commonly used empiric abx regimens (Dr. Reese) |
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Definition
| adults and children: IV ceftriaxone, IV vancomycin; neonates: IM ampicillin, IV cefotaxime with or w/o gentamicin; consider covering for listeria |
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Term
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Definition
| steroid; decrease: cerebral edema, ICP, vasculitis, cytokine release. associated with less hearing loss and better pt outcome from meningitis. |
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Term
| PK/PD principles involved in Rx bacterial meningitis (Dr. Reese) |
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Definition
| must penetrate CSF; must use adequate doses of abx; DOC based on EBM |
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Term
|
Definition
| uncommon condition; shares many features of acute meningitis but more likely to see: mental status changes, no pathonomonic presentation. |
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