Antiemetics & Growth Factors Flashcards

1
Q

central mechanism of chemotherapy-induced nausea & vomiting (CINV)

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

peripheral mechanism of chemotherapy-induced nausea & vomiting (CINV)

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

2 main neurotransmitters that stimulate the vomiting center in the brain

A
  1. serotonin [use 5-HT receptor antagonists]
  2. substance P/NK-1 [use NK-1 receptor antagonists]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

acute phase chemotherapy-induced nausea & vomiting (CINV)

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

delayed phase chemotherapy-induced nausea & vomiting (CINV)

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

anticipatory phase chemotherapy-induced nausea & vomiting (CINV)

A

*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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

breakthrough nausea & vomiting

A

*nausea and vomiting that occurs despite adequate anti-emetics
*often refractory to therapy:
-dopamine antagonists may be effective
-use a different mechanism to treat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

refractory nausea & vomiting

A

*nausea & vomiting that occurs despite adequate anti-emetics, INCLUDING breakthrough meds
*need to add additional therapy for subsequent cycles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

serotonin (5HT3) antagonists - overview

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

serotonin (5HT3) antagonists - adverse effects

A

*headache
*constipation or diarrhea
*EKG changes - concern with underlying arrhythmias or other drugs that prolong QTc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

serotonin (5HT3) antagonists - examples

A

*ondansetron (tablets, oral-dissolving tablets, IV)
*granisetron (tablets, IV, patch, subQ)
*palonosetron (IV or tablets - may be beneficial for acute and delayed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

neurokinin-1 (NK-1) receptor antagonists - overview

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

neurokinin-1 (NK-1) receptor antagonists - examples

A

*fosaprepitant (IV)
*aprepitant (tablet)
*combination NEPA (palonosetron & netupitant)
*rolapitant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

aprepitant - drug interactions & ADEs

A

*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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

corticosteroids for N/V

A

*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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

olanzapine for N/V

A

*2nd gen atypical antipsychotic
*blocks many different neurotransmitter receptors (dopamine, serotonin, etc)
*be aware of drug interactions

17
Q

dopamine receptor antagonists for breakthrough N/V

A

*phenothiazines (prochlorperazine, promethazine)
*butyrophenones (haloperidol, droperidol)
*substituted benzamide (metoclopramide)

18
Q

phenothiazines for breakthrough N/V

A

*phenothiazines are a type of dopamine receptor antagonist
*effective for delayed/breakthrough N/V
*ADEs - akathisia, dystonia, sedation

19
Q

substituted benzamides (metoclopramide) for breakthrough N/V

A

*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

20
Q

benzos for N/V

A

*examples - lorazepam, diazepam
*possess amnesic, anxiolytic, and sedative properties
*used for ANTICIPATORY NAUSEA
*not effective for preventing emesis and usually given with other antiemetics

21
Q

cannabinoids for N/V

A

*example - dronabinol
*ADEs - mood changes, dysphoria, memory loss, hallucinations
*used for anticipatory N/V

22
Q

anticholinergic (scopolamine) for N/V

A

*beneficial for nausea associated with movement
*ADEs - anticholinergic side effects (dry mouth, blurred vision, constipation, decreased sweating, etc)

23
Q

hematopoietic growth factors - functions

A
  1. regulate hematopoiesis - proliferation, differentiation, maturation
  2. effects on mature cells - increase chemotaxis, enhance phagocytosis, increase cytotoxic killing, improve responsiveness to antigens, enhance eosinophil function
24
Q

commercially available hematopoietic growth factors - categories

A
  1. filgrastim - target: G-CSF; cell target: neutrophils & WBCs
  2. sargramostim - target: GM-CSF; cell target: neutrophils & macrophages
  3. epoetin - target: erythropoietin stimulating agents; cell target: RBCs
  4. oprelvekin - target: thrombopoietin agents; cell target: platelets
25
Q

activity of granulocyte-colony stimulating factor (G-CSF)

A

*supports proliferation of neutrophils
*stimulates neutrophil function
*no effect on mature eosinophils and macrophages

note - drug name is filgrastim

26
Q

ADEs of G-CSF (filgrastim)

A

*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

27
Q

activity of granulocyte macrophage colony stimulating factor (GM-CSF)

A

*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

28
Q

ADEs of GM-CSF

A

*constitutional sx: fever, headache, myalgia, arthralgias
*bone pain
*skin reactions
*pleural and pericardial effusions

29
Q

activity of erythropoietin stimulating agents (ESAs)

A

*enhance RBC production
*decreases need for RBC transfusions
*pts should have Hb < 10 or Hct < 30%
*monitor iron stores
*requires 2-6 weeks

30
Q

ADEs of ESAs

A

*HTN
*headache
*increased tendency to clot vascular access
*iron deficiency anemia
*seizures
*achiness and cold sensation in long bones
*pyrexia

31
Q

activity of thrombopoiesis stimulating agents

A

*increases platelets in patients with CHRONIC immune thrombocytopenic purpura (ITP)
*not effective for acute thrombocytopenia
*examples: romiplostim (SQ) or eltrombopag (tablet)

32
Q

spleen tyrosine kinase (Syk)

A

*helps to reduce antibody-mediated destruction of platelets in chronic ITP
*example - fostamatinib (oral)
*watch for HTN, diarrhea, neutropenia