1. TM The EPEC-O Project Education in Palliative and End-of-life Care - Oncology The EPEC TM -O Curriculum is produced by the EPEC TM Project with major funding provided by NCI, with supplemental funding provided by the Lance Armstrong Foundation.

2. EPEC  – Oncology Education in Palliative and End-of-life Care – Oncology Module 3p: Symptoms – Nausea / vomiting Module 3p: Symptoms – Nausea / vomiting

3. Nausea / vomiting... l Definitions o Nausea is an unpleasant subjective sensation of being about to vomit. o Vomiting is the reflex expulsion of gastric contents through the mouth. l Definitions o Nausea is an unpleasant subjective sensation of being about to vomit. o Vomiting is the reflex expulsion of gastric contents through the mouth.

4. ... Nausea / vomiting l Impact very distressing:  Unpleasant awareness of nausea  Inability to keep food or fluids down  Acid and bitter tastes  Unpleasant smells of vomitus l Impact very distressing:  Unpleasant awareness of nausea  Inability to keep food or fluids down  Acid and bitter tastes  Unpleasant smells of vomitus

5. Key points l Pathophysiology l Assessment l Management l Pathophysiology l Assessment l Management

6. Pathophysiology l Nausea o Subjective sensation (easily learned) o Stimulation of:  Gastrointestinal lining  Chemoreceptor Trigger Zone (CTZ)  Vestibular apparatus  Cerebral cortex l Vomiting o Neuromuscular reflex l Nausea o Subjective sensation (easily learned) o Stimulation of:  Gastrointestinal lining  Chemoreceptor Trigger Zone (CTZ)  Vestibular apparatus  Cerebral cortex l Vomiting o Neuromuscular reflex

7. Pathophysiology CortexCortex Vestibular apparatus GI tract Chemoreceptor Trigger Zone (CTZ) Neurotransmitters l Neurokinin l Serotonin l Dopamine l Acetylcholine l Histamine Neurotransmitters l Neurokinin l Serotonin l Dopamine l Acetylcholine l Histamine Vomiting center

8. Causes l Metastases l Meningeal irritation l Movement l Mental anxiety l Medications l Mucosal irritation l Metastases l Meningeal irritation l Movement l Mental anxiety l Medications l Mucosal irritation l Mechanical obstruction l Motility l Metabolic l Microbes l Myocardial

9. Assessment l When do symptoms occur? l Acute versus chronic l Intermittent or constant l Associated with sights or smells l Eating patterns l Bowel patterns l Medications l When do symptoms occur? l Acute versus chronic l Intermittent or constant l Associated with sights or smells l Eating patterns l Bowel patterns l Medications

10. Management l Dopamine antagonists l Antihistamines l Anticholinergics l Serotonin antagonists l Neurokinin antagonists l Dopamine antagonists l Antihistamines l Anticholinergics l Serotonin antagonists l Neurokinin antagonists l Prokinetic agents l Antacids l Cytoprotective agents l Other medications Gralla R, et al. J Clin Oncol. 1999.

11. Chemotherapy nausea l Acute: o Occurs within 24 hours o Chemoreceptor trigger zone o Serotonin release in the gut l Delayed: o Occurs 24 hours to days later o Unclear mechanism l Acute: o Occurs within 24 hours o Chemoreceptor trigger zone o Serotonin release in the gut l Delayed: o Occurs 24 hours to days later o Unclear mechanism

12. Chemotherapy emetogenicity Emetogenic Class Incidence acute vomiting I Minimal (<10%) II Low (10-30%) III Mild (30-60%) IV Moderate (80-90%) V High (>90%)

13. Dopamine antagonists l Haloperidol l Prochlorperazine l Droperidol l Thiethylperazine l Promethazine l Haloperidol l Prochlorperazine l Droperidol l Thiethylperazine l Promethazine l Trimethobenzamide l Metoclopramide l Olanzapine l Perphenazine

14. Histamine antagonists (antihistamines) l Diphenhydramine l Meclizine l Hydroxyzine l Diphenhydramine l Meclizine l Hydroxyzine

15. Acetylcholine antagonists (anticholinergics) l Scopolamine

16. Serotonin antagonists l Ondansetron l Granisetron l Dolasetron l Palonosetron l Ondansetron l Granisetron l Dolasetron l Palonosetron

17. Neurokinin-1 antagonists l Aprepitant

18. Prokinetic agents l Metoclopramide l Domperidone l Macrolide antibiotics, e.g., erythromycin l Metoclopramide l Domperidone l Macrolide antibiotics, e.g., erythromycin

19. Antacids l Antacids l H 2 receptor antagonists o Cimetidine o Famotidine o Ranitidine l Proton pump inhibitors o Omeprazole o Lansoprazole l Antacids l H 2 receptor antagonists o Cimetidine o Famotidine o Ranitidine l Proton pump inhibitors o Omeprazole o Lansoprazole

20. Other medications l Dexamethasone 6 to 20 mg PO daily l Tetrahydrocannabinol 2.5 to 5 mg PO 3 times a day l Lorazepam 0.5 to 2 mg PO every 4 to 6 hours l Octreotide 10 micrograms per hr. via IV or SC infusion or 100 micrograms SC every 8 hrs. for bowel obstruction l Dexamethasone 6 to 20 mg PO daily l Tetrahydrocannabinol 2.5 to 5 mg PO 3 times a day l Lorazepam 0.5 to 2 mg PO every 4 to 6 hours l Octreotide 10 micrograms per hr. via IV or SC infusion or 100 micrograms SC every 8 hrs. for bowel obstruction

21. Summary Use comprehensive assessment and pathophysiology-based therapy to treat the cause and improve the cancer experience.