Objectives

1. Objectives By the end of this module you will • Have a better understanding of how physical and mental factors affect symptomatology • Be able to use this understanding in the treatment of patients suffering from nausea/vomiting and dyspnea • Incorporate skills and knowledge gained into your practice and teaching

2. Non-Pain Symptom Management James Hallenbeck, MD Assistant Professor of Medicine, Stanford School of Medicine Director, Palliative Care Services, VA Palo Alto HCS

3. Definition of a Symptom “A physical or mental phenomenon, circumstance or change of condition arising from accompanying a disorder and constituting evidence for it… specifically a subjective indicator perceptible to the patient and as opposed to an objective one (compare with sign).” The New Shorter Oxford English Dictionary, cited by The Oxford Textbook of Palliative Medicine Symptoms as clues, not experiences, not suffering

4. From the Patient’s Perspective- a Symptom Is What Is Bothersome

5. Disease As a Clue for the Symptom Disease process Symptom Questions to ask… How does the disease give rise to the symptom through local, central effects? What are emotional, cognitive and spiritual components of the patient’s illness?

6. What Symptoms? Constipation Diarrhea Peripheral Edema Nausea, vomiting Pruritus/itching Dyspnea Anxiety Anorexia Sleep disorders Cough Akathisia Dysphagia Anhedonia Death rattle/secretions Drooling Urinary Incontinence Rectal Incontinence Hiccups Flatulence Muscle spasms Confusion Memory Loss Visual problems Hearing loss Dysgeusia Colic Sexual dysfunction Polyuria Polydipsia Dizziness Dyspepsia Xerostomia Dry skin Dysarthria Dysphoria Dysuria Failure to thrive Fatigue Fear Fever Crying Hallucinations Halitosis Impotence Irritability Taste alterations Odor Mucositis Panic attacks Photosensitivity Restlessness Stomatitis Urinary frequency N=53, Oxford Textbook of Palliative Medicine: Index, 1998.

7. Nausea and Vomiting

8. So WHY do we have this disgusting problem?

9. Consider our Hungry Ancestors… What protects this guy from eating something poisonous?

11. Pearl for the Day… Rodents do not vomit!

12. Receptor Affinity Common Antiemetics Drug Dopamine 2 Musc. Chol. Histamine Scopolamine >10,000 .08 >10,000 Promethazine 240 21 2.9 Prochlorperazine 15 2100 100 Chlorpromazine 25 130 28 Metoclopramide 270 >10,000 1,000 Haloperidol 4.2 >10,000 1,600 The lower the number,the stronger this agent is at blocking this receptor Adapted from Perourka, Snyder

13. Causes of Nausea and Vomiting • Vestibular • Obstruction (Opioids) • Mind (Dysmotility) • Infection (irritation) • Toxins (taste and other senses)

14. VVestibular Apparatus • Complaint of nausea with head movement • Mediated by acetylcholine and histamine receptors • DOC(s): • Promethazine (supp) • Scopolomine (patch, injection) • Cyclizine (oral, injection) Most anticholinergic, antihistminic drugs will help!

15. OObstruction • Most common cause: constipation • May be caused by external or internal obstruction • In advanced malignant bowel obstruction external compression most common • May be mediated through both mechano and chemoreceptors • Doc(s) • True bowel obstruction • Controversy as to best drugs • Constipation- anti-constipation meds

16. MMind • Mediates emotional, cognitive aspects of nausea- anxiety, memory, meaning • Can be very powerful • Manipulating taste and other senses often helpful • Doc(s): • Lorazapam (poor solo agent) • Appetite stimulants • Megestrol, steroids, Cannibinoids

17. MDysMotility • Multiple causes • Opioids • Anticholinergic drugs • Stomach/bowel compression, infiltration • Upper intestinal dysmotility-very common, under appreciated • Doc(s): Prokinetics: • Metoclopramide (upper only) • Cisapride (upper and lower gut) • Senna (lower only)

18. IInfection/Irritation • Mediated through chemoreceptors- acetylcholine, histamine, serotonin • Gut and adjacent organ inflammation can trigger • DOC(s): Anticholinergic/antihistaminic agents, such as promethazine

19. TToxins • Most important- drugs we give • Various mechanisms of inducing nausea • Local irritant • NSAIDs • Changing blood levels (via CTZ) • opioids, ? SSRIs • Toxic blood levels • digoxin • Doc(s): depends on mechanism of action

20. Opioid Related Nausea Via two mechanisms: • Gut effect: Dysmotility of upper and lower gut • Doc(s): prokinetics • Effect on CTZ • Mediated through D2 receptor • Related to changing blood levels • Improves with steady state blood level • Doc(s): Haloperidol (po, inj.), Prochlorperizine (supp, po) No good evidence, rationale for using promethazine

21. 5HT3 Antagonists • Useful for certain forms of chemotherapy related nausea • May have other special uses: • In CTZ related nausea, where dopamine blockade contraindicated • ? Other refractory CTZ related causes • ? In certain GI cases • Very expensive currently

22. Dyspnea

23. Dyspnea • Common- 70% of dying patients in last six weeks of life • Traditional care for dyspnea largely palliative, as not curative • Focuses on lung physiology • Less attention to central processes • Pathophysiology of dyspnea poorly understood

24. Treating Dyspnea In addition to what you already know… • Local • Low-dose opioids • Fan, cool breeze • Central • Low-dose opioids • Benzodiazepines for anxiety • Address emotional, cognitive, spiritual factors

25. SUMMARY • Symptoms matter in their own right as expressions of patient suffering • Symptoms have their own “pathophysiology,” • As is true for treatment of disease, treatment of symptoms is tailored to this underlying physiology