Lec 6 Heme/Onc
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Lec 6 Heme/Onc
Lec 6: GI toxicities
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
What are the patient-related risk factors for CINV?
poor control with previous chemo
psychosocial (anxiety, depression, etc)
alcohol use history (<10 drinks/wk)
hx of motion sickness or morning sickness w/ pregnancy
What are the therapy-related risk factors for CINV?
emetogenic potential of chemo regimen
dose, route, and administration rate of agent
multiple chemotherapy cycles
What is acute CINV and what is its MOA?
occurs within 1st 24 hours of chemo
peaks in 5-6 hrs
: stimulation of dopamine & serotonin receptors
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
: stimulation of dopamine and serotonin receptors
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
: conditioned reflex - not d/t nueroreceptor stimulation
What is breakthrough CINV and what is its MOA?
occurs despite prophylactic treatment
requires the use of rescue therapy
Which drugs have high (>90% of patients) emetogenic risk?
Which drugs have moderate (> 30% of patients) emetogenic risk?
What classes of drugs are used in the prevention and management of CINV?
Discuss neurokinin-1 antagonists.
Emend (aprepitant, fosaprepitant)
approved in combination with other antiemetics for
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
: several case reports of ifosfamide-induced encephalopathy in pt receiving aprepitant
Discuss serotonin antagonists
Kytril (granisetron), Zofran (ondansetron), Aloxi (palonosetron) --> acute treatment
recognized as the foundation of CINV management
most commonly used meds to
: blocks release of serotonin from enterochromaffin cells in the GIT & blocks release of serotonin from receptors in the medulla
: 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
Whcih serotonin antagonist should be administered with a corticosteroid and be given as a 1 time dose on day 1 only?
: acute and delayed
: questionable inhibition of prostaglandin synthesis in cortex, decreased serotonin turnover in CNS, modulation of higher coritcal pathway; synergistic with seronitin antagonists and metoclopramide
: mood changes, anxiety, insomnia, increased appetite, hyperglycemia, mild fluid retention, perinieal, vaginal, and anal burning (rare- caused by too rapid of IV administration)
Discuss benzamide analogs.
Reglan (metoclopramide) and Tigan (trimethobenzamide)
: 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:
: EPS (dystonia, trismus), akathisia
Compazine (prochlorperazine) and Phenergan (promethazine)
: blocks dopamine and histamine receptors
: sedation, hypotension, akathisia, dystonia
prochlorperazine has greater efficacy for delayed nausea than serotonin antagonists
emetogenic chemo (mostly prn)
not very potent antiemetic in cancer pts -
: 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
: sedation, anticholinergic effects, hypotension (less common than w/ phenothiazines), EPS uncommon, QT prolongation (possibly w/ droperidol)
Lorazepam by itself has minmal to no activity as an antiemetic
: amnesia, sedation, hypotension, hallucinations, urinary incontinence, disinhibition, motor incoordination
: targets CB1 receptor in the CNS to directly block emesis; indirectly inhibits other NTs release in the emesis process
: metabolized by 2C9; may inhibit 3A4
: drowsiness, euphoria, dysphoria, mood changes, orthostatic hypotension, ataxia, hallucinations, time disorientation , increased appetite
: included in the most recent antiemetic guidelines; effective with
mild to moderate
tolerance usually develops to AEs
Discuss belladonna alkaloids.
: blocks ACh receptors in vestibular apparatus
: dry mouth, sedation, impaired eye accommodation
useful in pt whose n/v is
due to motion
What are non-pharm therapy for CINV?
acupuncture (shows mild improvement in vomiting, not nausea)
progressive muscle relaxation
acustimulation with wristband device
: smaller, more frequent meals; foods w/ reduced aroma; avoid spicy, fatty or salty foods; take anti-emetics prior to meals; eat gentle, comfort foods
What is the acute n/v treatment for Hesketh level of 4 or 5?
serotonin antagonist (zofran) AND dexamethasone AND (fos)aprepitant
What is the acute n/v treatment for Hesketh level of 3?
serotonin antagonist AND dexamethasone +/- (fos)aprepitant
What is the acute n/v treatment for Hesketh level of 2?
prochlorperazine OR dexamethasone OR metoclopramide
What is the acute n/v treatment for Hesketh level of 1?
no routine prophylaxis
What is the delayed n/v treatment for Hesketh level of 3, 4 or 5?
dexamethasone +/- aprepitant
What is the delayed n/v treatment for Hesketh level of 1 or 2?
no routine prophylaxis
What is the procedure for breakthrough emesis?
give drug from different class
around the clock - avoid prn
IV > PO
reassess prior to next cycle
What should be reassessed prior to the next cycle of chemo for breakthrough emesis?
increase dose/frequency of serotonin antagonist? change serotonin antagonist?
change chemo? (palliation)
consider addition of H2 blocker or PPI (dyspepsia)
When are anti-emetics best?
when given prophylactically
5-30 minutes prior to chemo