1. Seminar in Palliative Care September 26 – October 02, 2010 Salzburg, Austria in Collaboration with

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

3. Nausea / Vomiting Jamie H. Von Roenn, MD Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

4. Nausea / vomiting... Definition Definition Nausea is an unpleasant subjective sensation of being about to vomit Vomiting is the reflex expulsion of gastric contents through the mouth

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

6. Key points 1.Pathophysiology 2.Assessment 3.Management

7. Pathophysiology Nausea Nausea Subjective sensation (easily learned) Stimulation Gastrointestinal lining, CTZ, vestibular apparatus, cerebral cortex Vomiting Vomiting Neuromuscular reflex

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

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

10. Assessment When When Acute versus chronic Acute versus chronic Intermittent or constant Intermittent or constant Associated with sights or smells Associated with sights or smells Eating patterns Eating patterns Bowel patterns Bowel patterns Medications Medications

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

12. Chemotherapy nausea Acute Acute < 24 hr Chemoreceptor trigger zone Serotonin release in the gut Delayed Delayed 24 hr (may be days) Unclear mechanism

13. 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 %

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

15. Histamine antagonists (antihistamines) Diphenhydramine Diphenhydramine Meclizine Meclizine Hydroxyzine Hydroxyzine

16. Acetylcholine antagonists (anticholinergics) Scopolamine Scopolamine

17. Serotonin antagonists Ondansetron Ondansetron Granisetron Granisetron Dolasetron Dolasetron Palonosetron Palonosetron

18. Neurokinin-1 antagonists Aprepitant Aprepitant

19. Prokinetic agents Metoclopramide Metoclopramide Domperidone Domperidone Macrolide antibiotics, eg, erythromycin Macrolide antibiotics, eg, erythromycin

20. Antacids Antacids Antacids H 2 receptor antagonists H 2 receptor antagonistsCimetidineFamotidineRanitidine Proton pump inhibitors Proton pump inhibitorsOmeprazoleLansoprazole

21. Other medications Dexamethasone 6 – 20 mg PO daily Dexamethasone 6 – 20 mg PO daily Tetrahydrocannabinol 2.5 – 5 mg PO tid Tetrahydrocannabinol 2.5 – 5 mg PO tid Lorazepam 0.5 – 2 mg PO q 4 – 6 h Lorazepam 0.5 – 2 mg PO q 4 – 6 h Octreotide 10  g / hr IV / SC infusion Octreotide 10  g / hr IV / SC infusion or 100  g SC q 8 h for bowel obstruction

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