Antiemetics & Growth Factors Flashcards
central mechanism of chemotherapy-induced nausea & vomiting (CINV)
*chemotherapeutic agent activates the chemoreceptor trigger zone (CTZ) located in the area postrema in the brainstem
*activated CTZ invokes release of various neurotransmitters, which activates brainstem vomiting center
peripheral mechanism of chemotherapy-induced nausea & vomiting (CINV)
*chemotherapeutic agent causes GI irritation and damage to GI mucosa, resulting in release of neurotransmitters
*activated receptors mediated by vagal afferents send signals to brainstem vomiting center
2 main neurotransmitters that stimulate the vomiting center in the brain
- serotonin [use 5-HT receptor antagonists]
- substance P/NK-1 [use NK-1 receptor antagonists]
acute phase chemotherapy-induced nausea & vomiting (CINV)
*most common
*begins 1-2 hours, peaks 4-10 hours, resolves within 12-24 hours
*usually associated with high frequency and severity (intense)
*serotonin and neurokinin-1 antagonists are most effective in preventing against this
delayed phase chemotherapy-induced nausea & vomiting (CINV)
*begins 1-5 days after chemotherapy, peaks 48-72 hours
*less severe than acute nausea/vomiting, longer duration
*associated with high-dose cyclophosphamide, mitomycin-C, cisplatin, doxorubicin, and ifosfamide
*dexamethasone, olanzapine, and neurokinin-1 antagonists are most effective in preventing against this
anticipatory phase chemotherapy-induced nausea & vomiting (CINV)
*not associated with a time frame
*conditioned response
*usually prior history of severe N/V
*stimulated from environment
*occurs in up to 25% of patients
*often refractory to therapy (antianxiety meds may be helpful)
breakthrough nausea & vomiting
*nausea and vomiting that occurs despite adequate anti-emetics
*often refractory to therapy:
-dopamine antagonists may be effective
-use a different mechanism to treat
refractory nausea & vomiting
*nausea & vomiting that occurs despite adequate anti-emetics, INCLUDING breakthrough meds
*need to add additional therapy for subsequent cycles
serotonin (5HT3) antagonists - overview
*blocks serotonin both centrally and peripherally
*effective for ACUTE N/V but not any more effective for delayed N/V than other therapies
*most effective when given 30 min prior to administration of chemo
*increase efficacy when given with corticosteroids by adding different mechanism
serotonin (5HT3) antagonists - adverse effects
*headache
*constipation or diarrhea
*EKG changes - concern with underlying arrhythmias or other drugs that prolong QTc
serotonin (5HT3) antagonists - examples
*ondansetron (tablets, oral-dissolving tablets, IV)
*granisetron (tablets, IV, patch, subQ)
*palonosetron (IV or tablets - may be beneficial for acute and delayed)
neurokinin-1 (NK-1) receptor antagonists - overview
*MOA: inhibits substance P
*indicated for prevention of acute AND delayed CINV in combination with serotonin antagonists and corticosteroids
*part of combination regimen with a 5HT3-receptor antagonist + dexamethasone
neurokinin-1 (NK-1) receptor antagonists - examples
*fosaprepitant (IV)
*aprepitant (tablet)
*combination NEPA (palonosetron & netupitant)
*rolapitant
aprepitant - drug interactions & ADEs
*steroids should be decreased when using
*be cautious when using with agents metabolized by CYP3A4
*ADEs - asthenia/fatigue, nausea, hiccups, diarrhea, somnolence
note - aprepitant is a NK-1 receptor antagonist
corticosteroids for N/V
*most effective for delayed CINV
*increases appetite, improve mood and sense of well being
*immunosuppressive properties
*may increase differentiation of WBC and not used in AML
*ADEs: mood changes, anxiety, euphoria, headache, metallic taste
*dexamethasone given IV or PO (1:1)