Lec 6 Heme/Onc

  1. What mechanisms are involved in chemotherapy-induced n/v?
    • chemoreceptor trigger zone: chemical stimuli in CSF and blood (chemo)
    • neurotransmitter receptors in GIT & vagus nerve stimulation: chemo & GI compression
  2. What are the patient-related risk factors for CINV?
    • poor control with previous chemo
    • psychosocial (anxiety, depression, etc)
    • age <50
    • alcohol use history (<10 drinks/wk)
    • females
    • hx of motion sickness or morning sickness w/ pregnancy
  3. What are the therapy-related risk factors for CINV?
    • emetogenic potential of chemo regimen
    • dose, route, and administration rate of agent
    • multiple chemotherapy cycles
    • concomitant radiation 
  4. What is acute CINV and what is its MOA?
    • occurs within 1st 24 hours of chemo
    • peaks in 5-6 hrs
    • mechanism: stimulation of dopamine & serotonin receptors 
  5. What is delayed CINV and what is its MOA?
    • occurs > 18-24 hrs after chemo and up to 5 days later
    • peaks at 2-3 days post-chemo
    • mechanism: stimulation of dopamine and serotonin receptors
  6. What is anticipatory CINV and what is its MOA?
    • triggered by sights, smells, sounds
    • often due to poor past control
    • can occur at any time
    • mechanism: conditioned reflex - not d/t nueroreceptor stimulation
  7. What is breakthrough CINV and what is its MOA?
    • occurs despite prophylactic treatment
    • requires the use of rescue therapy
  8. Which drugs have high (>90% of patients) emetogenic risk?
    • cisplatin
    • dacarbazine
  9. Which drugs have moderate (> 30% of patients) emetogenic risk?
    • anthracyclines
    • carboplatin
    • cyclophosphamide
  10. What classes of drugs are used in the prevention and management of CINV?
    • neurokinin-1 antagonists
    • serotonin antagonists
    • corticosteroids
    • benzamide analogs
    • phenothiazines
    • butyrphenones
    • benzodiazepines
    • cannabinoids
    • belladonna alkaloids
  11. Discuss neurokinin-1 antagonists.
    • Emend (aprepitant, fosaprepitant)
    • aprepitant: acute/delayed
    • fosaprepitant: acute
    • approved in combination with other antiemetics for prevention of acute and delayed n/v
    • appropriate for pt receiving moderate emetogenic chemo (anthracycline & cyclophosphamide) & possibly other types of chemo associated w/ delayed CINV
    • substrate of CYP 3A4 
    • 3 days administration: CYP3A4 inhibitor
    • > 14 days administration: CYP3A4/CYP2C9 inducer
    • warning: several case reports of ifosfamide-induced encephalopathy in pt receiving aprepitant
  12. Discuss serotonin antagonists
    • Kytril (granisetron), Zofran (ondansetron), Aloxi (palonosetron) --> acute treatment
    • recognized as the foundation of CINV management
    • most commonly used meds to prevent and treat acute n/v
    • MOA: blocks release of serotonin from enterochromaffin cells in the GIT & blocks release of serotonin from receptors in the medulla
    • AE: h/a, constipation, asthenia, diarrhea, sedation; asymptomatic & transient ECG inteval abnormalities (PR, QT, ST prolongation & QRS widening)
    • studies show these drugs not very effective if used after day 1 of chemo
  13. Whcih serotonin antagonist should be administered with a corticosteroid and be given as a 1 time dose on day 1 only?
  14. Discuss corticosteroids.
    • decadron (dexamethasone): acute and delayed
    • MOA: questionable inhibition of prostaglandin synthesis in cortex, decreased serotonin turnover in CNS, modulation of higher coritcal pathway; synergistic with seronitin antagonists and metoclopramide
    • AE: mood changes, anxiety, insomnia, increased appetite, hyperglycemia, mild fluid retention, perinieal, vaginal, and anal burning (rare- caused by too rapid of IV administration)
  15. Discuss benzamide analogs.
    • Reglan (metoclopramide) and Tigan (trimethobenzamide)
    • MOA: blocks dopamine effect at chemoreceptor trigger zone, stimulates cholinergic activity in the gut therefore increasing gut motility, blocks peripheral serotonin receptors in the gut
    • highly emetogenic agents: requires high doses & combo w/ diphenhydramine/lorazepam
    • moderately/milk emetogenic agents: lower doses
    • AE: EPS (dystonia, trismus), akathisia
  16. Discuss phenothiazines.
    • Compazine (prochlorperazine) and Phenergan (promethazine)
    • MOA: blocks dopamine and histamine receptors
    • AE: sedation, hypotension, akathisia, dystonia
    • prochlorperazine has greater efficacy for delayed nausea than serotonin antagonists
    • effective with mild/moderately emetogenic chemo (mostly prn)
    • not very potent antiemetic in cancer pts - breakthrough meds
  17. Discuss butyrphenones.
    • Haloperidol
    • MOA: blocks dopamin receptors in the CTZ
    • at least equally efficacious as phenothiazines (binds differently due to chemical structure; alternative if phenothiazines fail)
    • useful for breakthrough n/v
    • AE: sedation, anticholinergic effects, hypotension (less common than w/ phenothiazines), EPS uncommon, QT prolongation (possibly w/ droperidol)
  18. Discuss benzodiazepines.
    • Lorazepam by itself has minmal to no activity as an antiemetic
    • useful to prevent anticipatory n/v
    • AE: amnesia, sedation, hypotension, hallucinations, urinary incontinence, disinhibition, motor incoordination 
  19. Discuss cannabinoids.
    • Dronabinol, Nabilone
    • MOA: targets CB1 receptor in the CNS to directly block emesis; indirectly inhibits other NTs release in the emesis process
    • Interactions: metabolized by 2C9; may inhibit 3A4
    • AE: drowsiness, euphoria, dysphoria, mood changes, orthostatic hypotension, ataxia, hallucinations, time disorientation , increased appetite
    • Dronabinol: included in the most recent antiemetic guidelines; effective with mild to moderate emetogenic chemo
    • tolerance usually develops to AEs
  20. Discuss belladonna alkaloids.
    • scopolamine patch
    • MOA: blocks ACh receptors in vestibular apparatus
    • AE: dry mouth, sedation, impaired eye accommodation
    • useful in pt whose n/v is positional or due to motion
  21. What are non-pharm therapy for CINV?
    • acupuncture (shows mild improvement in vomiting, not nausea)
    • guided imagery
    • music therapy
    • progressive muscle relaxation
    • psychoeducational support
    • acustimulation with wristband device
    • ginger
    • dietary changes: smaller, more frequent meals; foods w/ reduced aroma; avoid spicy, fatty or salty foods; take anti-emetics prior to meals; eat gentle, comfort foods
  22. What is the acute n/v treatment for Hesketh level of 4 or 5?
    serotonin antagonist (zofran) AND dexamethasone AND (fos)aprepitant
  23. What is the acute n/v treatment for Hesketh level of 3?
    serotonin antagonist AND dexamethasone +/- (fos)aprepitant
  24. What is the acute n/v treatment for Hesketh level of 2?
    prochlorperazine OR dexamethasone OR metoclopramide
  25. What is the acute n/v treatment for Hesketh level of 1?
    no routine prophylaxis
  26. What is the delayed n/v treatment for Hesketh level of 3, 4 or 5?
    dexamethasone +/- aprepitant 
  27. What is the delayed n/v treatment for Hesketh level of 1 or 2?
    no routine prophylaxis
  28. What is the procedure for breakthrough emesis?
    • give drug from different class
    • around the clock - avoid prn
    • IV > PO
    • reassess prior to next cycle
  29. What should be reassessed prior to the next cycle of chemo for breakthrough emesis?
    • add aprepitant?
    • increase dose/frequency of serotonin antagonist? change serotonin antagonist?
    • add anxiolytic?
    • change chemo? (palliation)
    • consider addition of H2 blocker or PPI (dyspepsia)
  30. When are anti-emetics best?
    • when given prophylactically
    • 5-30 minutes prior to chemo
Card Set
Lec 6 Heme/Onc
Lec 6: GI toxicities