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
1. fosaprepitant (IV)
2. aprepitant (tablet)
3. combination NEPA (palonosetron & netupitant)
4. 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)
olanzapine for N/V
*2nd gen atypical antipsychotic
*blocks many different neurotransmitter receptors (dopamine, serotonin, etc)
*be aware of drug interactions
dopamine receptor antagonists for breakthrough N/V
*phenothiazines (prochlorperazine, promethazine)
*butyrophenones (haloperidol, droperidol)
*substituted benzamide (metoclopramide)
phenothiazines for breakthrough N/V
*phenothiazines are a type of dopamine receptor antagonist
*effective for delayed/breakthrough N/V
*ADEs - akathisia, dystonia, sedation
substituted benzamides (metoclopramide) for breakthrough N/V
*blocks dopamine in the CTZ and peripherally (increases esophageal sphincter tone, gastric emptying, and transit through small bowel)
*ADEs - EPS, restlessness, sedation, fatigue, nausea and diarrhea
benzos for N/V
*examples - lorazepam, diazepam
*possess amnesic, anxiolytic, and sedative properties
*used for ANTICIPATORY NAUSEA
*not effective for preventing emesis and usually given with other antiemetics
cannabinoids for N/V
*example - dronabinol
*ADEs - mood changes, dysphoria, memory loss, hallucinations
*used for anticipatory N/V
anticholinergic (scopolamine) for N/V
*beneficial for nausea associated with movement
*ADEs - anticholinergic side effects (dry mouth, blurred vision, constipation, decreased sweating, etc)
hematopoietic growth factors - functions
- regulate hematopoiesis - proliferation, differentiation, maturation
- effects on mature cells - increase chemotaxis, enhance phagocytosis, increase cytotoxic killing, improve responsiveness to antigens, enhance eosinophil function
commercially available hematopoietic growth factors - categories
- filgrastim - target: G-CSF; cell target: neutrophils & WBCs
- sargramostim - target: GM-CSF; cell target: neutrophils & macrophages
- epoetin - target: erythropoietin stimulating agents; cell target: RBCs
- oprelvekin - target: thrombopoietin agents; cell target: platelets
activity of granulocyte-colony stimulating factor (G-CSF)
*supports proliferation of neutrophils
*stimulates neutrophil function
*no effect on mature eosinophils and macrophages
note - drug name is filgrastim
ADEs of G-CSF (filgrastim)
*BONE PAIN (esp in lumbar, sternal, and pelvic areas)
-common during initiation of therapy and times of rapid growth
-pain responsive to acetaminophen or NSAIDs
-may be prevented with loratidine
activity of granulocyte macrophage colony stimulating factor (GM-CSF)
*stimulates CFU-GM and CFU-GEMM to increase neutrophiles, macrophages, monocytes, and eosinophils
*no clinically significant activity on other cell lines
note - G-CSF is used way more b/c of ADEs of GM-CSF
ADEs of GM-CSF
*constitutional sx: fever, headache, myalgia, arthralgias
*bone pain
*skin reactions
*pleural and pericardial effusions
activity of erythropoietin stimulating agents (ESAs)
*enhance RBC production
*decreases need for RBC transfusions
*pts should have Hb < 10 or Hct < 30%
*monitor iron stores
*requires 2-6 weeks
ADEs of ESAs
*HTN
*headache
*increased tendency to clot vascular access
*iron deficiency anemia
*seizures
*achiness and cold sensation in long bones
*pyrexia
activity of thrombopoiesis stimulating agents
*increases platelets in patients with CHRONIC immune thrombocytopenic purpura (ITP)
*not effective for acute thrombocytopenia
*examples: romiplostim (SQ) or eltrombopag (tablet)
spleen tyrosine kinase (Syk)
*helps to reduce antibody-mediated destruction of platelets in chronic ITP
*example - fostamatinib (oral)
*watch for HTN, diarrhea, neutropenia
