Nausea & Vomiting: Choosing Antiemetics. Dr. Robin Love March 2015

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1 Nausea & Vomiting: Choosing Antiemetics Dr. Robin Love March

2 Objectives Learn a practical approach to management of nausea and vomiting in palliative care Practical approach but there is very little science to back this up 2

3 Theoretical Approach 1. Identify the cause 2. Identify the physiological pathway 3. Identify the neurotransmitter 4. Choose the most potent antagonist 5. Choose the best route of administration 6. Titrate the dose carefully, give the dose regularly, review frequently 7. If symptoms persist, change or add additional treatments Oxford Textbook of Palliative Medicine 3

4 Cerebral High CNS Sights, Smells Memories Vestibular Opioids Cerebellar Tumor Increased Intracranial Press Primary or Met. Tumor M Downing Integrative Vomiting Centre (IVC) Chemoreceptor Trigger Zone Toxic Ca Emetogenic Infection Radiation Drugs Chemotherapy Opioids Digoxin, etc Biochemical Uremia Hypercalcemia GI Tract Vagal Distension Over-eating Gastric Stasis Extrinsic Press. Obstruction High, mid, low Constipation Chemical Irritants Blood, drugs 4

5 Cerebral High CNS GABA, cannabinoids Chemoreceptor Trigger Zone D 2, 5HT 3 Vestibular H1, Ach m Integrative Vomiting Centre (IVC) GI Tract Vagal Increased Intracranial Press Ach, H 1, 5HT 2, 5HT 3 cannabinoid D 2, 5HT 3, 5HT 4, 5

6 Cerebral High CNS Benzodiazepines Cannabinoids, Vestibular H1 antagonist Dimenhydrinate Methotrimeprazine Olanzapine Anticholinergic Scopolamine Atropine Increased Intracranial Press Dexamethasone Gravol methotrimeprazine? VP Shunt M Downing (updated feb 2015) Integrative Vomiting Centre (IVC) Anticholinergic Scopolamine Atropine H1 Antagonist Dimenhydrinate Methotrimeprazine 5HT2 Antagonist Olanzapine Methotrimeprazine 5HT3 Antagonist Ondansetron Chemoreceptor Trigger Zone D2 Antagonist Prochlorperazine Haloperidol Methotrimeprazine Chlopromazine Olanzapine Metoclopromide 5HT3 Antagonist Ondansetron GI Tract Vagal D2 Antagonist Gastrokinetics Metoclopromide Domeperidone Phenothiazines Methotrimeprazine 5HT4 Agonist Metoclopromide 5HT3 Antagonist Ondansetron Metoclopramide Octreotide Dexamethasone CB1 cannabinoids 6

7 Cerebral High CNS Benzodiazepines Cannabinoids Vestibular H1 antagonist Dimenhydrinate Methotrimeprazine Olanzapine Anticholinergic Scopolamine Atropine Increased Intracranial Press Dexamethasone Gravol methotrimeprazine? VP Shunt M Downing Integrative Vomiting Centre (IVC) Anticholinergic Scopolamine Atropine H1 Antagonist Dimenhydrinate Methotrimeprazine 5HT2 Antagonist Olanzapine Methotrimeprazine 5HT3 Antagonist Ondansetron Chemoreceptor Trigger Zone D2 Antagonist Prochlorperazine Haloperidol Methotrimeprazine Chlopromazine Olanzapine Metoclopromide 5HT3 Antagonist Ondansetron GI Tract Vagal D2 Antagonist Gastrokinetics Metoclopromide Domeperidone Phenothiazines Methotrimeprazine 5HT4 Agonist Metoclopromide 5HT3 Antagonist Ondansetron Metoclopramide Octreotide Dexamethasone CB1 cannabinoids 7

8 Framework : How do we organize our approach? All textbooks are organized differently. Cause? Receptor? ( these are not consistent in different texts) Drug class? Site of action Chemical type medical class ie antipsychotic, prokinetic Drug we are most familiar with? Random guess? 8

9 Practical Syndrome or Best Etiology Drug 9

10 Antiemetic Drugs Wide variety Several classes Much more complex than Analgesics Some drugs affect more than one receptor Some drugs act in more than one location 10

11 Classes of Antiemetic Drugs: 1. Dopamine Antagonist A. Antipsychotics Drug Haloperidol Principal Action CTZ Prochlorperazine CTZ Chlorpromazine CTZ / IVC? Methotrimeprazine CTZ / IVC / Gut? Olanzapine 5HT2 plus Haloperidol the drug of choice: - most potent at CTZ, most specific Dopamine agent - lower side effects - available tablets, liquid, sc, iv, im - use low doses mg q8h 11

12 Classes of Antiemetic Drugs: 1.Dopamine Antagonist B. Prokinetic Drug Metoclopramide Domperidone Principal Action CTZ / GI GI Metoclopramide the drug of choice: - multiple effects ( CTZ, D 2 in Gut, 5HT 3, 5HT 4 ) - acts centrally and peripherally - tablets, liquid, sc, iv - watch for akathisia - doses (..40) mg qid 12

13 Classes of Antiemetic Drugs: 2. H1 antihistamine Drug Diphenhydramine Dimenhydrinate Promethazine Hydroxyzine Principal Action VC, vestibular VC, vestibular UGI tract, VC UGI tract, VC Drug of Choice? - promethazine sc at lower doses 13

14 Classes of Antiemetic Drugs: 3. Anticholinergic Drug Scopolamine (hyoscine) glycopyrrolate Hydroxyzine Principal Action Vestibular / Vomiting Center/GI tract Periphery/ GI tract Scopolamine available as transdermal or sc, iv, im Glycopyrrolate less CNS side effects 14

15 Classes of Antiemetic Drugs: 4. Steroids Drug Dexamethasone Prednisone Methylprednisolone Principal action??????? - Dexamethasone po, sc - Mechanism of action is not clear - Also often add this in for difficult nausea 15

16 Classes of Antiemetic Drugs: 5. Cannabinoids Drugs Nabilone Many new choices of cannabinoids Principal action VC VC Role is unclear, but can be very helpful in some vomiting cases Lots of receptors still to be sorted out 16

17 Classes of Antiemetic Drugs: 6. 5-HT3 antagonists. Drug Ondansetron Granisetron Principal action UGI tract? CNS Reduces gastric secretions? Other effects Constipating 17

18 Classes of Antiemetic Drugs: 7. Benzodiazepines Drugs Lorazepam Midazolam Principal action adjunctive Little direct antiemetic effect, but they reduce anxiety, akathisia and anticipatory nausea 18

19 Classes of Antiemetic Drugs 8. miscellaneous Drugs Octreotide Omeprazole Ranitidine Antacids Principal action Antisecretory etc Proton pump inhibitor H2 receptor antagonist Propofol? CTZ or VC 19

20 Non Drug Measures Nasogastric tube Gastrostomy tube ( venting) 20

21 Family and Nursing measures Food type Odors Present small portions only of what they want Palliative Diet eat what they feel like eating Educate patient and family about futility of pushing calories 21

22 Common Syndromes of Nausea 22

23 1. Chemically Induced Causes Opioids Digoxin Cancer treatment Anticonvulsants Antibiotics Toxins ( tumor products, ischemic bowel) Metabolic ( Ca, liver or renal failure ) Treatment Haloperidol Prochlorperazine Chlorpromazine Methotrimeprazine Metoclopramide Dexamethasone Lorazepam Ondansetron 23

24 2. Motion Induced Causes Opioids Gastroparesis CNS tumor or metastases Treatment Promethazine (phenergan) Dimenhydrinate (gravol) Scopolamine/Hyoscin e Methotrimeprazine Doxylamine/pyridoxi ne (Diclectin) 24

25 3. Gastric Stasis Causes Opioids Anticholinergic drugs Ascites Autonomic dysfunction Hepatomegaly Gastritis Obstruction/ mechanical Treatment Prokinetics Metoclopramide Domperidone Dopamine antag. Haloperidol etc. Reduce secretions scopolamine Octreotide Omeprazole etc 25

26 4.Vagal Induced - stretch/distortion of viscera Causes Constipation Obstruction Mesenteric metastases Liver metastases Ureteric obstruction Treatment Prokinetics Metoclopramide Domperidone Methotrimeprazine Dimenhydrinate Scopolamine 26

27 5. Increased Intracranial Pressure Causes Tumor Edema Intracranial bleed Infection ( Aids) Treatment Dexamethasone Dimenhydrinate Methotrimeprazine lorazepam 27

28 General Strategy ( if no obvious cause) do you feel full and bloated like you ate too much or is it more of a queasy car sick kind of feeling? metoclopramide haloperidol 28

29 General Strategy ( if no obvious cause) 1. Metoclopramide mg sc q 6h 2. +/ - Haloperidol mg sc q6h 3. + Antihistamine 4. + Dexamethasone 5. + Scopolamine 6. 3 rd line including ondansetron, nabilone, diclectin. 29

30 Intractable Nausea May require sedation Lorazepam, midazolam, chlorpromazine, methotrimeprazine, etc. Propofol may be effective but not practically available Gastrostomy venting tube 30

31 Pearls Optimize the dose depending on side effects Re-evaluate possible cause Add 2 nd line that targets a different receptor (usually add drugs, don t just substitute as there may be additive effects) Continuous medication may be more effective May need multiple drug combinations in high doses Don t forget the practical measures (reduce intake etc.) 31

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