Mascara Alkyl Sulfonate

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  1. busulfan chemical workings
    • bifunctional alkylating agent
    • SN2 rxn
  2. busulfan especially toxic to:
    • myeloid cells 
    • hematopoietic stem cells
  3. historic use of busulfan
    chronic oral therapy for chronic myelogenous leukemia
  4. current use of busulfan
    allogenic stem cell transplantation combined with cylophosphamide or fludarabine
  5. busulfan route of admin and why
    • iv preferred over oral
    • dec in risk hepatic veno-occlusive disease (VOD)/sinosoidal obstruction syndrome (SOD)
    • avoid variation in bioavailability
  6. busulfan PK
    • distribution into CSF
    • hepatic metabolism (gluthione conjugation and CYP 3A4
  7. busulfan drug interactions
    • APAP (glutathione depletion
    • metronidazole
  8. busulfan AEs
    • seizures
    • pulmonary fibrosis
    • SOS/VOD
    • myelosuppression
    • secondary malignancies
    • N/V
  9. busulfan seizure prophylaxis
    • phenytoin
    • levetiracetam
    • benzodiazepine
  10. busulfan emetogenicity
  11. nitrosoureas produce ___ and ____ in aqueous solution under physiological conditions
    carbonium ion intermediates that alkylate nucleophiles

    isocyanates that can carbamoylate nucleophiles
  12. what influences the mechanism of decomposition in water
    the substituents on the N atoms
  13. carmustine dosage forms
    IV and intracranial implant
  14. carmutine uses
    • brain tumors
    • slavage regimen in HL an NHL

    less common: melanoma, multiple myeloma
  15. carmustine adverse effects
    • prolonged bone marrow suppresion
    • pulmonary fibrosis
  16. which agent contains a lot of alcohol?
    • carmustine
    • avoid meds that cause disulfiram like rxns
  17. lomustine dosage form
  18. common uses
    primary and metastatic brain tumor
  19. lomustine AEs
    • prolonged myelosuppresion
    • N/V
    • pulmonary toxicity (high accumulative dose)
    • secondary malignancies
    • reversible hepatotoxicity
    • kidney damage (dec in kidney size, azotemia, renal failure with long term use)
  20. lomustine emetogenicity
  21. lomustine clinical pearls
    • only dispense enough for one course at a time
    • monitor CBCs and adjust dose based on previous nadirs
    • give on an empty stomach
    • only repeat course when bone marrow has recovered
  22. triazenes are what type of alkylating agent
    monofunctional pro-drugs
  23. dacarbazine uses
    • common: Hodgkin's lymphoma
    • uncommon:malignant melanoma
  24. dacarbazine AEs
    • myelosuppresion
    • hepatotoxicty
    • anaphylaxis
    • secondary malignancies
    • N/V
    • infusion site pain
    • alopecia
  25. dacarbazine emetogenicity
  26. difference between activation of temozolomide and dacarbazine
    temozolomide activation rxn is spontaneous and non-enzymatic (happens in all physiological tissue)
  27. cytotoxic effects of triazenes manifested by
    alkylation of guaninine in DNA at the O6 and N7 positions
  28. temozolomide uses
    • common: newly diagnosed glioblastoma
    • other: refreactory anaplastic astrocytoma, metastatic melanoma, metastatic CNS lesions
  29. temozolomide route of admin
    typically oral (100% bioavailability)
  30. temozolomide AEs
    • myelosuppression
    • N/V
    • alopecia
    • headache
    • secondary malignancies
  31. temozolomide emetogenicity
  32. temozolomide clinical pearls
    • need prophylaxis for PCP (with concomitant radiation phase)
    • take 1 hr before radiation in initial phase
    • swallow caps on empty stomach
  33. platinum coordination complexes: what is used to prevent nephrotoxicty and why
    • chloride diuresis
    • in plasma, Cl concentration is high and platinum compound is unionized
    • when passes into cell Cl concentration is low and the platinum compound is ionized and toxic
  34. cisplatin uses
    • versatile
    • testicular
    • head/neck
    • ovarian
    • cervical
    • lung
  35. cisplatin AEs
    • N/V
    • nephrotoxicity
    • infertility
    • mild myelosuppresion
  36. cisplatin clinical pearls
    • give taxanes before platinum agents (less neutropenia)
    • use adequate IV hydration ± Mg, K to protect kidneys
    • need aggressive antiemetic regimen
    • always call MD for doses >100 mg/m2
  37. carboplatin compared to cisplatin
    • 10x as soluble in water
    • rate of hydrolysis much slower
    • less nephrotoxic and emetogenic
  38. how to dose carboplatin
    • mg = AUC (GFR + 25)
    • calvert formula
  39. carboplatin common uses
    • ovarian (in combo with paclitaxel or docetaxel)
    • small and non-small cell lung cancer
    • head and neck cancer
  40. carboplatin side effects
    • more myelosuppression than cisplatin
    • neurotoxicity
    • nephrotoxicity
    • dec in K and Mg
    • N/V
    • anaphylactic rxn
  41. oxaliplatin AEs compared to cisplatin
    less nephrotoxic, hematotoxic, and ototoxic than cisplatin
  42. oxaliplatin uses
    • common: colon cancer, metastatic cancer
    • less common: pancreatic cancer
  43. oxaliplatin AEs
    • neurotoxicity
    • hypersensitivity
    • pulmonary fibrosis
    • hepatotoxicity
  44. oxaliplatin clinical pearls
    • dilute with only D5W (not NS)
    • peripheral sensory neuropathy is dose limiting
  45. oxaliplatin neurotoxicity phases
    • acute: reversible, cold-induced; may cause pharyngolaryngeal spasms
    • chronic: improvement may take several mo to yrs
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Mascara Alkyl Sulfonate
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