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APHON Review
Pharm and Chemo
| Question | Answer |
|---|---|
| In what decade was chemotherapy first used to treat childhood cancer? | 1960's |
| What was the 5 year survival rate for all childhood cancers diagnosed in the 1960's compared to the 1990's? | 1960's: 28% 1990's: 68% (result of incorporating anticancer drugs into treatment regimens that previously relied only on surgery or radiotherapy. |
| Define combination chemotherapy? | multidrug combination regimens |
| Purpose of combination chemotherapy? | 1. overcome drug resistance to individual agents 2. broader range of coverage (single agent: <60% cure rate; combination: >95% cure rate) |
| Define adjuvant chemotherapy? | chemotherapy given to patients without evidence of residual disease after surgery or radiation. |
| Purpose of adjuvant chemotherapy? | prevent metastatic recurrence by eliminating micrometastatic tumor deposits in patients at high risk of relapse. |
| Define dose intensity? | Most anticancer drugs have a steep dose-reponse curve. The higher the dose, the greater the response. Limited by drug toxicity. |
| Purpose of dose intensity? | Maximum tolerated dose at the shortest possible intervals. |
| History of alkylating agents | 1.oldest antineoplastic drugs 2.sulfur mustard gas was used during WWII and soldiers exposed were later found to have very low WBC counts 3. 1940's several pts with advanced lymphomas were given the less toxic form, nitrogen mustard, IV 4. effectivenes |
| Mechanism of action for alkylating agents | convalent bonding of alkyl group to important cellular macromolecules. this leads to a. damage to DNA template; b. inhibition of DNA replication and transcription |
| List alkylating agents | Mechlorethamine (nitrogen mustard), Cyclophosphamide, Ifosfamide, Melphalan, Lomustine, Carmustine, Busulfan, Cisplatin, Carboplatin, Dacarbazine, Procarbazine |
| List toxicities from cyclophosphamide and ifosfamide? | myelosuppression, n/v, alopecia, hemorrhagic cystitis, nephrotoxicity, neurotoxicity, sterility |
| Signs of nephrotoxicity from cyclophosphamide? | renal tubular effect water retention |
| Treatment for toxicity from cyclophosphamide and ifosfamide? | aggressive hydration, frequent bladder emptying, Mesna (2-mercaptoethane sulfonate NA) |
| Signs of nephrotoxicity from ifosfamide? | proximal tubular damage, Fanconi's syndrome (amino aciduria, glucosuria, proteinuria) |
| Prevention for nephrotoxicity from cyclophosphamide and ifosfamide? | hydration monitor renal function |
| Signs of neurotoxicity from ifosfamide (20%)? | somnolence, disorientation, lethargy, seizures attributed to chloracetaldehyde (relative of chloral hydrate) which crosses the blood brain barrier |
| Prevention for neurotoxicity from ifosfamide? | avoid concomitant sedative agents |
| Treatment for neurotoxicity from ifosfamide? | methylene blue - prevents systemic formation of chloracetaldehyde from crossing into CNS |
| Define cyclophosphamide and ifosfamide? | inactive prodrugs that require biotransformation by hepatic enzymes |
| Define Cisplatin and Carboplatin? | Platinum compunds, heavy metal complexes that cause platination of DNA (like alkylation), Intrastrand crosslinks between neighboring guanines |
| Nephrotoxicity from Cisplatin significant or mild? | significant |
| Nephrotoxicity from Carboplatin significant or mild? | mild |
| Ototoxicity (irreversible) from Cisplatin significant or mild? (high range hearing) | mild |
| Ototoxicity (irreversible) from Carboplatin significant or mild? (high range hearing) | significant |
| Peripheral neuropathy from Carboplatin significant or mild? | significant |
| Peripheral neuropathy from Cisplatin significant or mild? | mild |
| N/V from Carboplatin significant or mild? | significant |
| N/V from Cisplatin significant or mild? | mild |
| Myelosuppression from Carboplatin significant or mild? | mild |
| Myelosuppression from Cisplatin significant or mild? | dose-limiting toxicity |
| List antimetabolites? | Methotrexate, Mercaptopurine (6-MP), Thioguanine (6-TG), Cytarabine, Fluorouracil |
| Define antimetabolites? | "Fraudulent substrates", close structural analogs of vital intermediates in the synthesis of nucleic acids and proteins |
| Define Methotrexate? | Most widely used in pediatric oncology Given IV, PO, IM, SC, IT |
| Mechanism of action of Methotrexate? | Structural analog of folic acid, Inhibits dihydrofolate reductase (enzyme responsible for converting folates to active form, tetrahydrofolate), Depletes pools of reduced folate essential for DNA synthesis |
| Med given to help protect kidneys and bladder from metabolite of methotrexate? | Leucovorin (folic acid), Given in high concentrations to out compete methotrexate for carrier proteins |
| Methotrexate levels are drawn why? | to determine if the DOSE and DURATION of leucovorin is adequate |
| Signs of methotrexate toxicities and treatments? | myelosupression (GCSF, neupogen), orointestinal mucositis (pain mgmt, mouth care), nephrotoxicity (vigorous hydration, alkalinization of urine, carboxypeptidase - G2) |
| Define carboxypeptidase - G2? | recombinant bacterial enzyme which catabolizes methotrexate to inactive metabolites |
| Define Mercaptopurine (6-MP)? | first purine analog |
| Define Thioguanine (6-TG)? | amino analog of 6-MP |
| Mechanism of action of (6-MP and 6-TG) | converted to ribonucleotides that inhibit purine biosynthesis |
| Define antitumor antibiotics? | originally isolated from the microbial broth of the soil microorganisms, Streptomyces; bind to DNA by intercalation, producing DNA strand breaks |
| List antitumor antibiotics? | Anthracyclines (Doxorubicin, Daunomycin, Idarubicin); Bleomycin; Dactinomycin |
| Mechanism of action of Anthracyclines (Doxorubicin, Daunomycin, Idarubicin)? | bind tightly to double stranded DNA; intercalate causing toppoisomerase breaks in DNA; undergo chemical reduction yielding reactive free radical intermediates |
| Signs of toxicity from Anthracyclines (Doxorubicin, Daunomycin, Idarubicin)? | myelosuppression, mucositis, radiation recall (potentiate radiation reactions in many tissues), acute and chronic cardiac toxicity |
| Define ACUTE anthracycline cardiac toxicity? | within 24 hrs, arrhythmias, conduction abnormalities, transient |
| Define CHRONIC anthracycline cardiac toxicity? | congestive cardiomyopathy (max cumulative dose 450mg/m2 for doxorubicin; 700mg/m2 for daunomycin); children ,5 y/o greater risk than older children; girls > boys |
| Treatment for CHRONIC anthracycline cardiac toxicity? | dexrazoxane - prevents radical formation; serial EKG and ECHO |
| List plant alkaloids? | Taxanes (Paclitaxel, Docetaxel); Epipodophyllotoxins (Etoposide, Teniposide); Vinca alkaloids (Vincristine, Vinblastine, Vinorelbine) e.g periwinkle |
| Mechanism of action of vinca alkaloids? | bind to tubulin, protein that forms microtubules; inhibits mitotic spindle formation, causing metaphase arrest during mitosis |
| Toxicities of vinca alkaloids? | neurotoxicity - loss of deep tendon reflexes, neuritic pain (muscular cramping, jaw pain), parasthesias, wrist and foot drop, autonomic nerve involvement (constipation, paralytic ileus, urinary retention). ACCIDENTAL INTRATHECAL ADMIN. MAY BE FATAL. |
| Mechanism of action of Etoposide? | strand breakage produced by inhibiting the enzyme topoisomerase II |
| Toxicities of Etoposide? | myelosuppression, secondary leukemias (median time to presentation 30 months, 5-12% risk in children with ALL treated with high cumulative doses on a weekly or twice weekly schedule). |
| List two monoclonal antibodies? | Rituximab (Rituxan) and Gemtuzumab (Mylotarg) |
| Mechanism of action of Rituximab (Rituxan)? | directed against the CD20 antigen on B-lymphocytes; CD20 regulates cell cycle initiation and functions as a calcium channel; binds to the antigen on the cell surface, activating complement-dependent B-cell cytotoxicity; used in NHL (CD 20+ B-cell) |
| Toxicities of Rituximab (Rituxan)? | severe (occationally fatal) infusion-related reactions; usually within 30-120 minutes and may include hypotension, angioedema, bronchospasm, hypoxia, urticaria; SEVERE: pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction. |
| Mechanism of action of Gemtuzumab (Mylotarg)? | antibody to CD33 antigen, which is expressed on leukemic blasts in 80% of AML patients; binds to the CD33 antigen, resulting in internalization of the antibody-antigen complex. |
| Toxicities of Gemtuzumab (Mylotarg)? | infusion related reactions like rituximab; petechiae, rash, hyper/hypotension, hyperkalemia, hyperbilirubinemia, weakness, peripheral edema |
Created by:
nseltzer
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