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

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

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

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

... 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

Key points 1.Pathophysiology 2.Assessment 3.Management

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

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

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

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

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.

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

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 %

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

Histamine antagonists (antihistamines) Diphenhydramine Diphenhydramine Meclizine Meclizine Hydroxyzine Hydroxyzine

Acetylcholine antagonists (anticholinergics) Scopolamine Scopolamine

Serotonin antagonists Ondansetron Ondansetron Granisetron Granisetron Dolasetron Dolasetron Palonosetron Palonosetron

Neurokinin-1 antagonists Aprepitant Aprepitant

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

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

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

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