Wake Cancer Induced Nausea And Vomiting And Growth Factors

Front 1

Adverse Events of IL-11

Back 1

- Tachycardia (19-30%)
- Atrial arrhythmias (60-75%)
- Peripheral edema (60-75%)
- Headache (41%)
- Dizziness (38%)
- Insomnia (33%)
- Fatigue (30%)
- Fever (35%)
- Rash (25%)
- Dyspnea (48%)

Front 2

IL-11
Oprelvekin
(Neumega)
Activity

Back 2

- Promotes megakaryocyte production
- Prevents severe thrombocytopenia

* This is not really used because you can just give platelet transfusions

Front 3

Adverse Events of EPO

Back 3

- Hypertension (24%)
- Headache (16%)
- increase tendency to clot vascular access
- Iron deficiency anemia
- Seizures
- Achiness and cold sensation in long bones
- Pyrexia (38% of AZT-treated patients)

Front 4

Activity of EPO
Erythropoietin (Procrit/Epogen)

Back 4

Enhances RBC production (inc HCT)
Decreases need for RBC transfusions
Patients should have Hgb < 10 g/dL or HCT < 30%
Monitor iron stores
Requires 2-6 weeks to see response

Front 5

Darbopoietin (AraNesp)

Back 5

- Larger molecule with more carbohydrate groups to allow for slower elimination
- Dose: indicated 2.5 mcg/kg SQ weekly or 500 mcg SQ every 3 weeks
- Should be used in patients receiving CHEMOTHERAPY with NO INTENT FOR CURE
- New FDA guidelines state that all patients should receive medication guide prior to therapy

Front 6

Hematopoietic Growth Factors

Back 6

Regulate hematopoiesis
- Proliferation
- Differentiation
- Maturation
Effects of Colony Stimulating Factors on mature cells
- Increase chemotaxis
- Enhance phagocytosis
- Increase cytotoxic killing
- Improve responsiveness to antigens
- Enhance eosinophil function

Front 7

Activity of G-CSF
Filgrastim (Neupogen)

Back 7

- Supports proliferation of neutrophils
- Stimulates neutrophil function
- No effect on mature eosinophils and macrophages

Front 8

Filgrastim (Neupogen®)
Adverse Events

Back 8

* Bone Pain:
- Occurs in the lumbar, sternal and pelvic areas
- Common during initiation of therapy and times of rapid growth
- May reflect increased bone marrow activity
- Pain responsive to acetaminophen or NSAIDs
- Only attributable adverse event of G-CSF

Front 9

Pegylated Filgrastim
(Neulasta)

Back 9

- larger chemical structure makes clearance slower and therefore allows administration once after chemotherapy
- Cleared by neutrophils, as the white blood cells recover

Front 10

Activity of GM-CSF
Sargramostim (Leukine®)

Back 10

- Stimulates CFU-GM and CFU-GEMM to increase neutrophils, macrophages, monocytes, eosinophils
- No clinically significant activity on other cell lines (RBCs and platelets)

Front 11

Sargramostim (Leukine®)
Adverse Events

Back 11

- Constitutional Symptoms
- Fever, headache, myalgias, arthralgias
- Fever responds well to antipyretics
- May have less fever with SQ administration
- Bone pain
- Skin reactions
- Pleural and pericardial effusions
- First-dose effect

Front 12

Potential Mechanisms of CINV

Back 12

- Stimulation of chemoreceptor trigger zone (CTZ)
- Peripheral mechanisms
- Cortical mechanisms
- Vestibular mechanisms
- Alterations of taste and smell

Front 13

Central Mechanism
Proposed Pathophysiology of CINV

Back 13

- Chemotherapeutic agent activates the CTZ located in the area postrema in the brainstem
- Activated CTZ invokes release of various neurotransmitters, which activates brainstem vomiting center

Front 14

Peripheral mechanism
Proposed Pathophysiology of CINV

Back 14

- Chemotherapeutic agent causes GI irritation and damage to GI mucosa, resulting in release of neurotransmitters (serotonin)
- Activated receptors mediated by vagal afferents send signals to brainstem vomiting center

Front 15

Which Neurotransmitters respond will for acute CINV?

Back 15

- Serotonin
- Substance P

Front 16

Which Neurotransmitters are good for delayed or rescuing N/V?

Back 16

- Dopamine
- Histamine
- Acetylcholine

Front 17

Serotonin (5HT3) Receptor Antagonists
Activity

Back 17

- 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 minutes prior to administration of chemotherapy (PREVENTATIVE)
- Increase efficacy when given with corticosteroids (administration with steroids increases efficacy from 60% to 90%

Front 18

What is acute CINV?

Back 18

N/V within the 1st 24 hours after chemotherpy

Front 19

5HT3 Receptor Antagonists
Adverse Events

Back 19

- Headache (too little serotonin)
- Constipation
- Diarrhea
- EKG changes – concern only with underlying arrhythmias

Front 20

Postfix = -setron

Back 20

5HT3 Receptor Antagonists
-
- Ondasetron (Zofran)
- Granisetron (Kytril)
- Granisetron (Sancusco)... patch
- Dolasetron (Anzemet)
- Palonosetron (aloxi)

Front 21

Neurokinin-1(NK-1) Receptor Antagonists
Activity

Back 21

- Inhibits Substance P
- Indicated for the prevention of acute and delayed CINV in combination with serotonin antagonists and corticosteroids

Front 22

Aprepitant (Emend)

Back 22

- NK-1 Receptor Antagonists
- this is part of a combination therapy for those at severe risk for acute nausea/vomiting

Front 23

Aprepitant (Emend)
Adverse Events

Back 23

- Asthenia/fatigue (18%)
- Nausea (13%)
- Hiccups (11%)
- Diarrhea (10%)
- Somnolence

Front 24

Drug Interactions with Emend

Back 24

- Decrease steroids by 50% IV, 25% po
- Use with caution when administering agents that are metabolized by CYP3A4 becuase it could increase the concentrations of other drugs

Front 25

Dopamine Receptor Antagonists

Back 25

Phenothiazines
Butyrophenones
Substituted benzamide

Front 26

metoclopramide (Reglan®)
drug class

Back 26

Substituted benzamide

Front 27

droperidol (Inapsine®)
drug class

Back 27

Butyrophenones

Front 28

prochlorperazine (Compazine®)
promethazine (Phenergan®)
drug class

Back 28

Phenothiazines

Front 29

Phenothiazines
Activity

Back 29

Effective for delayed nausea/vomiting

Front 30

Phenothiazines
Adverse Events

Back 30

- akathisia – lorazepam can help
- dystonia – diphenhydramine or benztropine can help
- sedation – more common with promethazine

Front 31

Which is more potent: Prochloperazine or Premethazine?

Back 31

Prochlorperazine is a more potent antiemetic in cancer patients but has a higher incidence of akathisia and dystonia

Front 32

Substituted Benzamides
Action

Back 32

Blocks dopamine in the CTZ and peripherally
- increases esophageal sphincter tone
- improves gastric emptying
- increases transit through small bowel

Front 33

Substituted Benzamides
Adverse Events

Back 33

- Extrapyramidal Side Effects (EPS)
- restlessness
- sedation
- fatigue
- nausea and diarrhea (dexamethasone may decrease diarrhea)

Front 34

Benzodiazepines
Action

Back 34

- Used for anticipatory nausea
- Not effective for preventing emesis and is usually given with other antiemetics

Front 35

Benzodiazepines

Back 35

- retrograde amnesic
- anxiolytic
- sedative

Front 36

Anticholinergics

Back 36

i.e. Scopolamine
- Beneficial for nausea associated with movement
- side effects...no secretions

Front 37

Cannabinoids
Dronabinol (Marinol)

Back 37

- Less effective than metoclopramide but more effective than phenothiazines
- Not effective with highly emetogenicity
- Beneficial with younger patients
- Significantly increases your appetite while decreases N/V

Front 38

Cannabinoids
Dronabinol (Marinol)
Adverse Events

Back 38

- mood changes
- dysphoria
- memory loss
- hallucinations
- blurred vision
- hypotension
- tachycardia

Front 39

Corticosteroids
Adverse events

Back 39

- mood changes
- anxiety
- euphoria
- headache
- metallic taste
- abdominal discomfort

Front 40

Corticosteroids
Dexamethasone

Back 40

- Increases appetite, improve mood and sense of well being
- Immunosuppression
- May increase the differentiation of WBC and therefore is not given in acute myelogenous leukemia (AML)