alklators, anthracyclines

Card Set Information

Author:
merazar15
ID:
226904
Filename:
alklators, anthracyclines
Updated:
2013-07-13 22:17:12
Tags:
Pharm hem onc
Folders:

Description:
hem/onc
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user merazar15 on FreezingBlue Flashcards. What would you like to do?


  1. Alklators categories of drugs:
    • Nitrosoureas- can cross the BBB
    • Bis(chlorethyl)amines
    • Aziridines- bladder CA
    • Alkyl Sulfonate
    • others
  2. Nitrosoureas drugs:
    • Carmustine  (BiCNU), (Gliadel)- brain CA- crosses BBB
    • Lomustine (CCeeNU)- brain CA- crosses BBB
    • Semustine – taken off the market
  3. Bis(chlorethyl)amines drugs:
    • Cyclophosphamide (Cytoxan)- most freq used
    • Mechlorethamine  (Mustargen)
    • Chlorambucil (Leukeran)
    • Melphalan (Alkeran)
    • Ifosfamide  (Ifex)
  4. Aziridines (bladder ca) drugs:
    • Thiotepa (Thioplex)
    • Triethylenemelamine
  5. Alkyl sulfonate:
    • Busulfan (Myleran)
    • Treosulfan (Ovastat)
  6. the other guys:
    • Dacarbazine (DTIC)  (DTIC-Dome)
    • Procarbazine (Matulane)
    • Temozolomide (Temodar)
    • Bendamustine  (Treanda) – non hodgkins
  7. which drug is #1 for metastatic brain CA?
    • Temozolomide (Temodar)- #1 for metastatic brain CA- on exam
    • PO, crosses BBB, palliative care,
  8. Alkylator MOA:
    • Gets inside the nuclear membrane
    • Transfer alkyl (chemical)  groups to DNA (adds alkyl group to DNA)
    •      Damages to DNA 
    •      Activate proapoptotic proteins (p53)
    •      Leads to cell death
    • Cell cycle phase nonspecific
    • Cells in G1 and S phases are most susceptible
  9. Additional MOA for Nitrosourease:
    • cross BBB, brain CA
    • Undergo carbamoylation – on exam
    •      Transfer of carbamoyl (NH2CO) groups to an amino group (amino acids)
    •      Lysine residues of proteins
    •      Product of this reaction (carbamoylated protein)
    •         Limits the ability of the CA cell to repair DNA
    •         Limits/lacks cross-resistance btwn nitrosoureas & other members of this class
  10. Alkylators kinetics:
    • Oral dosage forms:  Cyclophosphamide, melphalan, chlorambucil, & busulfan·  
    • Lomustine (PO only)
    • IV & PO: Cyclophosphamide
  11. Nitrosoureas kinetics:
    • Highly lipid soluble
    •     Readily cross the blood-brain barrier
    •       Useful in the treatment of brain tumors 
    • Most have short half-lives
    •     Mechlorethamine 
    •        Half-life: 10 minutes
    •     Exceptions:
    •         Cyclophosphamide (8 hrs)
    •         Ifosfamide (15 hrs)
  12. indications for cyclophosphamide:
    • Lymphomas
    • Leukemias
    •    Increase in WBC, decrease platelets, decrease RBC -> Blasts
    •       WBC eats up everything around it
    • Multiple myeloma
    •    Plasma cell dysplasia (form of B cell)
    •    Sxs- crab ( hypercalcemia, renal dysfunction, anemia, bone pain)
    • Mycosis fungoides
    •     Cutaneous T-cell Lymphoma
    •        Most lymphomas are B cells
    • Neuroblastoma
    • Retinoblastoma
    • Cancers of the lung, breast, ovary
    • Immunosuppression
    •     Lupus, RA, MS
  13. melphalan indication:
    • Multiple myeloma 
    • Ovarian (epithelial) carcinoma
  14. #1 regime for multiple myeloma:
    Velcade + Reulimic (Leuolidamide)
  15. Chlorambucil indication:
    • Chronic lymphocytic leukemia
    • Non-Hodgkin's lymphomas
  16. Procarbazine indication:
    Hodgkins’s disease
  17. Carmustine indication:
    • Malignant lymphomas
    • Multiple myelomas
    • Cancers of the brain, gastrointestinal (GI) tract, skin (melanoma)
  18. Lomustine indication:
    • Hodgkin's disease
    • Cancers of the breast, brain, lung, skin
  19. Bendamustine indication:
    Chronic lymphocytic leukemia (CLL), NHL
  20. Diffuse Large B-cell lymphoma #1 regime:
    R-CHOP(Rituximab, cyclophosphamide, DOXOrubicin, VinCRIStine, Prednisone)
  21. Breast CA-
    gene:
    triple neg breast CA:
    regime:
    drugs:
    • BRCA gene
    • PR, ER, HER2 = triple negative breast CA
    • Regime= surgery, hormonal (Tamofen, HER2- Herceptin), chemotherapy
    • DOXOrubicin/ Cyclophosphamide) q 21 days followed by T (PACLItaxel) weekly + Trastuzumab
  22. Chronic Lymphocytic leukemia (non hodgkins lymphoma) #1 regime:
    • Fludarabine/Cyclophosphamide + Rituximab
    • Aka: FCR
  23. Glioblastoma #1 regime:
    Temozolomide
  24. Hodgkins lymphoma #1 regime:
    ABVD: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine
  25. Acute myeloid leukemia #1 regime:
    High-dose Cytarabine/DAUNOrubicin
  26. CI for alklators:
    • Severe leukopenia, thrombocytopenia (myelosuppression)
    • Cyclophosphamide
    • Pregnancy
    • Lactation
  27. SE for alkylators:
    • N/V
    • Alopecia
    •        Cyclophosphamide – highest grade agent to cause these SE
  28. Serious SE of alkylators:
    • Myelosuppression
    • Pulmonary toxicity
    •     Nitrosoureas and busulfan·         Nephrotoxicity and Bladder toxicity
    •     Cyclophosphamide and ifosfamide
    • Leukemia (rare)·        
    • Hemorrhagic cystitis (which one causes it)
    •     Caused by a metabolite of cyclophosphamide and ifosfamide
    •        Acrolein
  29. management for hemorrhagic cystitis:
    • Increasing fluid intake
    • Administering an agent that binds with acrolein and forms a nontoxic compound
    •    Sulfhydryl donors
    •        N-acetylcysteine (used for tylenol OD
    •        Mesna – (decreases hemo cystitis)
    •            Antioxidant
  30. Which alkylator has the highest potential to cause N/V?
    • carmustine
    • cisplatin
  31. Antiemetic therapy:  given before chemotherapy
    • 5-HT3 (Zofran)
    • Dexamethasone (steroid)
    • NK1 antagonist
    • Lorazepam
    • H2 blocker or PPI
  32. mech of resistance for alkylators:
    • DNA repair
    • Decreased entry of drug into the cell
    • Inactivation of the alkylating agent by glutathione
  33. cross-resistance of alkylators:
    • Common among the alkylating agents
    • Exception of the nitrosoureas (which one lacks cross resistance)
  34. Anthracyclines:
    what is super imp to remember about the Anthracyclines?
    • Cytotoxic anticancer agents
    •    Damage DNA
    •    Generate free radicals
    • Also grouped under a larger class
    •    Antitumor antibiotics
    •    Never used as antibiotics

    cardiotoxic!
  35. anthracycline drugs:
    • Doxorubicin (Adriamycin)
    • Daunorubicin (Cerubidine)- acute leukemias
    • Idarubicin (Indamycin PFS)
    • Epirubicin (Ellence)
    • Aclarubicin
    • Mitoxantrone (Novantrone)
  36. MOA of anthracyclines:
    • Intercalate into and inhibit the DNA-topoisomerase II complex after the nicking phase (prevents resealing, increases fragments, and apoptosis)
    • Produce free radicals (damage cell membranes, proteins, and lipids)
    •    Leads to apoptosis
    • DNA intercalation (attaches right to DNA):  Inhibits transcription and replication
    • Topoisomerase II (Top II)
    •    Plays a key role during DNA synthesis
    •    Nicking and resealing the DNA helix so that it does not become tangled during replication
  37. anthracyclines kinetics:
    Doxorubicin:
    Idarubicin:
    • Doxorubicin is a prodrug
    •    Idarubicin is the active metabolite
    • Doxorubicin (reduces cardiotox)
    •    First anthracycline to be encapsulated in liposomes (Doxil®)
    •    Facilitate targeted delivery of the drug
    •      Avoid cardiotoxicity
    • Eliminated through hepatic metabolism via multiple mechanisms
    •    Patients with significant hepatic impairment
    •       Dose adjustments should be considered
    • Idarubicin
    •    Only anthracycline that can be given orally
  38. indications for Doxorubicin:
    • Hodgkin's disease (ABVD) (criteria: “owl eye cells”)
    • Non-Hodgkin's lymphoma (RCHOP)·   
    • Acute leukemias    
    • Sarcomas·        
    • Cancers of the breast (AC), lung, stomach, thyroid
  39. indication for Daunorubicin:
    Acute leukemia
  40. indication for Idarubicin:
    • Acute leukemia
    • breast CA
  41. indication for Epirubicin:
    • Lymphoma
    • Cancers of the lung, breast, ovary, stomach
  42. indication for Mitoxantrone: 2nd line
    • Prostate cancer
    •     PSA values: >4 bad,  >10 awful  
    • Transrectal bx
    •   Gleeson grading 
    •   If low grade: prostectomy + radiation
    •   If late stage: medical or chemical (desease testosterone) castration, prostectomy + radiation
    •       T level must be < 50
    •       Or give RN analogue (Lupron) ·     
    • Non-Hodgkin's lymphoma·        
    • MS
  43. SE of anthracyclines:
    • Nausea and vomiting
    • Reversible Alopecia
    • Mucositis or stomatitis
    • Soft tissue necrosis
    •     Extravasation (BBW) – doxorubicin, idarubicin, epirubicin, daunorubicin)
    • Myelosuppression
  44. what is Dexrazaoxane? (what it does & its utility)
    Is a tx regime for cytotoxin extravasations
  45. BBW for anthracyclines:
    • cardiotoxicity
    • caused by free radicals generated by anthracyclines
    • Cause peroxidation of the cardiac sarcoplasmic reticulum
    •     Leading to a Ca2+-dependent cardiac necrosis
    • Selective for cardiac tissue Bc it Lacks catalase
    •     Which Neutralize these free radicals
    • Use with caution in patients with cardiac disease
    • Can occur both acutely and chronically·  
    •   Acute toxicity
    •     Characterized by abnormal electrocardiograms (ECGs) and reductions in systolic function·    
    •   Chronic toxicity (Greatest concern)
    •       Cumulative and dose related
    •       Manifests as congestive heart failure
    •       Very high mortality rate
  46. how can you minimize the cardiotoxicity caused by anthracyclines?
    • Limitations on doses used
    • Max. cumulative dose of doxorubicin is 550mg/m2 or 450mg/m2 in patients who are receiving RT
    • Use of liposomal formulations and adjuvant agents·        
    •    Doxil® (pegylated liposomal doxorubicin)
    • Monitoring LVEF
    •     <30 to 40%·        
    •     Therapy should not be instituted
  47. SE of Doxorubicin:
    Red discoloration of saliva, sweat, tears, urine, and feces
  48. what is Dexrazoxane?
    • Used to minimize cardiotoxicity – eats up the free radicals ·        
    •   The generation of free radicals by anthracyclines is iron dependent
    •        Dexrazoxane chelates iron that is bound in anthracycline complexes
    •          Prevents the formation of the free radicals that damage the myocardium·     
    • Considered in adult patients who have received ≥300 mg/m2 of doxorubicin-based therapy·        
    • Does not appear to impair the antitumor activity
  49. unique about Mitoxantrone:
    • Has a chemical structure that is distinct from that of the anthracyclines
    • Believed to be less cardiotoxic than the anthracyclines
    • It does not generate free radicals
  50. DI of antracyclines:
    • Trastuzumab (Herceptin):          
    •      Increases the cardiotoxic effects of anthracyclines
  51. Mech of resistance of anthracyclines:
    • Drug efflux through P-glycoprotein (Pgp-170) or multidrug-resistant (MDR) gene
    • Altered levels or mutations in topoisomerase II
    • Increased glutathione
    • Free radical scavenger
    • Increased glutathione peroxidase activity
    • Decreased concentration of glucose-6-phosphate (G6P) dehydrogenase

What would you like to do?

Home > Flashcards > Print Preview