1. Nausea, Vomiting and Constipation Senior Academic Half Day Final Year Medical Students 4 th March 2011

2. Introductions: WE! Dr Sarah MacLaran, Consultant in Palliative Medicine UHCW - Coventry/Rugby & Coventry Myton Hospice Dr Jo Clerici, ST3 Palliative Medicine Registrar Coventry Myton Hospice Jaime Miks, Palliative Care Pharmacist, UHCW – Coventry and The Myton Hospices (Warwick/Coventry)

3. Introductions: YOU! Final Year Medical Students? Exams are looming...? Your priorities are passing your exams and surviving your House Jobs? You hope that this session will be helpful, memorable and worthwhile?

4. Aims of SAHD Course Integrate understanding of pharmacology & relevant use of commonly used medicines Learn how to prescribe most appropriate drug in context of individual patient’s symptoms Emphasise importance of safe prescribing Demonstrate knowledge of drugs to control common symptoms (benefits & dangers) Be able to use BNF to prescribe safely

5. Objectives for this session Learning how to manage N&V and constipation in order to prepare you for: 1.Your Pharmacology exam 2.Your Written Finals 3.Your Clinical Finals 4.Being a House Officer

6. Nausea and Vomiting

7. Definitions Nausea: Unpleasant feeling of need to vomit accompanied by autonomic symptoms (pallor, cold sweat, salivation, tachycardia, diarrhoea) Retching : Rhythmic laboured spasmodic movements of the diaphragm & abdo muscles (usually occurs with Nausea and results in Vomiting) Vomiting: The forceful propulsion of gastric contents through the mouth

8. Why is Treating N& V so important? Common Affects up to 70% patients with adv Cancer Many conditions Ranked highly distressing

10. Treating Nausea and Vomiting Relies on: Being able to recognise patterns of N&V Identifying likely cause in individual patients Understanding mode of action of commonly used anti-emetics Prescribing most appropriate antiemetic Choosing most appropriate route Negotiating with patient to ensure compliance

11. Asking the right questions Nausea? Retching? Vomiting? When: did it start? Time(s) of day? Constant/not? What: does vomit look like? Amount? Blood? How: did it start? How has it been treated so far? Why: Exacerbating (& relieving) factors

12. Principles of treating N&V Treat reversible causes for N&V Appropriate Drug Appropriate Route Appropriate Prescription: Regularly? Re-evaluate every 24-48 hrs

13. Syringe Drivers CSCI of SC meds over 24hrs If vomiting Not just for terminal care Home/ NH/ Hospital/ Hospice

14. Drugs we will concentrate on today

15. 1.Metoclopramide? 2.Domperidone? 3.Cyclizine? 4.Ondansetron? Receptor Action(s): a.Anti-histamine and Anti-muscarinic b.5HT3-Antagonist c.D2-Antagonist, 5HT4-Agonist: gastric motility agent d.D2-Antagonist gastric motility agent, which does NOT cross the Blood-Brain-Barrier Main Side Effect(s): i.Sedation, dry mouth, slow bowel transit ii.Constipation, headache iii.Few SEs (?rarely GI upset; abdo cramps, incr Prolactin) iv.Extra-pyramidal SEs, abdo cramps, incr Prol.

16. 1.Metoclopramide 2.Domperidone 3.Cyclizine 4.Ondansetron Receptor Action(s): 1.D2-Antagonist, 5HT4-Agonist: gastric motility agent 2.D2-Antagonist gastric motility agent, which does NOT cross the Blood-Brain-Barrier 3.Anti-histamine and Anti-muscarinic 4.5HT3-Antagonist Main Side Effect(s): 1.Extra-pyramidal SEs, abdo cramps, incr Prol. 2.Few SEs (?rarely GI upset; abdo cramps, incr Prolactin) 3.Sedation, dry mouth, slow bowel transit 4.Constipation, headache

17. Extra-Pyramidal Side Effects Akathisia Dystonia Tardive Dyskinesia Parkinsonism – Tremor – Rigidity – Bradykinesia = Restlessness = Prolonged muscle contraction = Abnormal unintentional movements, usually after prolonged use of drug

18. Drug combinations to avoid: IV Metoclopramide + IV Ondansetron: may cause serious cardiac arrhythmias Metoclopramide/Domperidone + Cyclizine Metoclopramide/Domperidone are motility agents while Cyclizine slows down GI transit

19. Putting the Theory into practice: Mechanisms of Nausea & Vomiting

20. Diagram of the Pathways of Emesis Higher Centres “Antiemetic” + - Centre enk - Vestib System H 1 Ach m CTZVom Centre D 2 5HT 3 H 1 Ach m Vagus Liver D2 Viscera/Serosa 5HT 3 & 4

21. Practical Exercise

22. Patterns of Nausea & Vomiting 1.Gastric Stasis 2.Other GI or Visceral irritation 3.Chemical or Metabolic 4.Motion Sickness 5.Raised Intra-Cranial Pressure 6.Unknown or Multiple causes

23. 1. Gastric Stasis Symptoms Epigastric fullness Early satiety Large volume vomits (?projectile) Hiccups Regurgitation (also if moving term ill pt) (?Minimal) Nausea quickly relieved by vomiting

24. 1. Gastric Stasis Contributing factors: Stomach emptying problems (eg Autonomic: eg Diabetes, Gastritis, Peptic Ulcer) Compression of gastric outflow (eg Tumour, Hepatomegaly, Ascites) Drug Side-Effects (eg Anti-Cholinergics, Opioids)

25. 1. Treating Gastric Stasis Treatment Reduce volume of oral intake: Little & often Reduce Gastric secretions: PPI (eg Omeprazole) Pro-kinetic agents: Dopamine D2-Antagonists: Metoclopramide (also 5HT4 agonist) Domperidone

26. 2. Other GI or Visceral irritation Symptoms: Due to the GI or Visc irritation (eg Constipation) Constant Nausea Less or variable Vomiting ?‘Fullness’

27. 2. Other GI or Visceral irritation Stimulation of Vagus / Gut 5HT3 receptors Contributing factors: GI or Visceral irritation: Pharyngeal irritation (eg Tumour/ Sputum/ Candida) Stretch receptors of: GI or GU Tract (eg Constipation, Bowel/ Ureteric obstruction) Visceral capsules (eg Hepatomegaly)

28. 2. Treating GI or Visceral N&V Treatment Address cause (eg Constipation) Anti-Cholinergic (vs Vagus) Cyclizine 5HT3-Antagonist Ondansetron

29. 3. Chemical or Metabolic N&V Characteristics: Constant nausea Less or variable vomiting

30. Stimulation of CTZ: D2 and 5HT3 receptors Contributing factors: Chemical: Drugs (many: esp Opioids, Antibiotics, Digoxin, NSAIDs, SSRIs, Chemotherapy) Metabolic (eg Renal / Liver failure, Hypercalcaemia of Malignancy, Hyponatraemia, sepsis) 3. Chemical or Metabolic N&V

31. 3. Treating Chemical/ Metabolic N&V Dopamine D2-Antagonist: Metoclopramide 5HT3-Antagonist Ondansetron

32. 4. Motion Sickness Characteristics: Vomiting on movement Dizziness ?Nystagmus

33. 4. Motion Sickness Stimulation of Vestibular System: H 1 & ACh m receptors Contributing factors: Stimulation of vestibular system Opioids can increase vestibular sensitivity ?Intracerebral cause

34. 4. Treating Motion Sickness Anti-Histamine and Anti-Cholinergic Agents: Cyclizine

35. 5. Raised Intracranial Pressure Characteristics: Symptoms worse in the morning? Headache Nausea Vomiting (?projectile)

36. 5. Raised Intracranial Pressure Stimulation of the Vomiting Centre: H 1 & ACh m receptors Any cause of Raised ICP eg: Intracranial SOL (primary / secondary tumours) Skull Metastases Intracranial Haemorrhage Meningeal infiltration

37. 5. Treating N&V due to Raised ICP Anti-Histamine and Anti-Cholinergic Agents: Cyclizine Depends on cause: eg ?SOL: ?Steroids ?Radiotherapy

38. 6. Unknown or Multiple Causes Non-Drug Measures: Address anxiety as a trigger Minimise smells (eg perfume, cooking, fungating tumour) Try cool fizzy drinks (?more palatable than hot still drinks) Acupuncture / Acupressure Ginger Hypnotherapy

39. 6. Treating N&V of Unknown cause Anti-Histamine and Anti-Cholinergic Agents: Cyclizine

40. Prescribing Exercise

41. Rows will do different scenarios (?Fictional) Name, DOB, Hospital ID, Allergies Most appropriate Antiemetic Drug (?cause) Most appropriate Route Correct Dose & Frequency using BNF Appropriate use of ‘Additional instructions’ box Sign & date your prescription! The person in the row behind you will mark your prescription! (Front row will mark Back row!)

42. 1.It’s 5am on a Med Ward. You are the FY1 on duty. You are called to Gladys, a 79 year old woman with lung cancer, who looks distressed, clutching her vomit bowl. She’s waiting to go to Nursing Home as she cannot manage at home. This is not the first morning she has been like this. She also has a headache. 2.Heather is a 70 year old lady with breast cancer with bone metastases. She has arrived in Casualty feeling very nauseated and generally unwell. At times she appears a little confused. She is on a large number of tablets. 3.James is a 64 year old man with advanced pancreatic cancer. He is admitted to hospital having been vomiting for the last week. He is only able to tolerate very small amounts orally and his abdomen feels bloated. He vomits with every meal and occasionally after he has only been drinking. Each time he vomits he brings up large amounts of fluid. He tells you he is often troubled by hiccups.

43. 4.Caroline is a 33 year old lady who is normally fit and well. She has had a mild cold recently. Last night she became much worse with the onset of dizziness. She tried to cope at home by putting herself to bed, but she has become so nauseated and incapacitated that she asked her husband to bring her to Casualty. She vomited several times on the way to Hospital. 5.Thomas is a 63 year old gentleman with prostate cancer which has metastasised to his spine. He developed spinal cord compression 3 weeks ago and now only has limited movement in both his legs. He is now waiting for a package of care to be set up so that he can go home again. He has been feeling nauseated for the last few days and been off his food for the last week. He has had difficulty opening his bowels since he came into hospital particularly in the last week. His abdomen feels bloated and uncomfortable.

44. Marking the Prescribing Exercise! The person in the row behind you will mark your prescription! (Front row will mark the Back row!) /4(?Fictional) Name, DOB, Hospital ID, Allergies /1Most appropriate Antiemetic Drug (?cause) /1Most appropriate Route /2Correct Dose & Frequency using BNF /1Approp use of Additional instructions’ box /1Prescription has been signed & dated 10

45. Accurate Prescription CYCLIZINE 150mg CSCI Dilute in Water for Injections 24hr DrDo-no-wrong 5.3.10 5 6

46. Accurate Prescription METOCLOPRAMIDE 10mg IV Stop if develops abdominal cramps TDS DrDo-no-wrong 5.3.10 5 6

47. 1.Metoclopramide 2.Domperidone 3.Cyclizine 4.Ondansetron Receptor Action(s): 1.D2-Antagonist, 5HT4-Agonist: gastric motility agent 2.D2-Antagonist gastric motility agent, which does NOT cross the Blood-Brain-Barrier 3.Anti-histamine and Anti-muscarinic 4.5HT3-Antagonist Main Side Effect(s): 1.Extra-pyramidal SEs, abdo cramps, incr Prol. 2.Few SEs (?rarely GI upset; abdo cramps, incr Prolactin) 3.Sedation, dry mouth, slow bowel transit 4.Constipation, headache

48. Drug combinations to avoid: IV Metoclopramide + IV Ondansetron: may cause serious cardiac arrhythmias Metoclopramide/Domperidone + Cyclizine Metoclopramide/Domperidone are motility agents while Cyclizine slows down GI transit

49. Specialist Palliative Care Be aware that these other drugs are sometimes used by the SPCT as Antiemetics Haloperidol Levomepromazine Hyoscine hydrobromide Olanzapine

50. Nausea & Vomiting Summary Treat reversible causes for N&V Remember 5 main patterns of N&V Appropriate Drug Appropriate Route Appropriate Prescription: Regularly? Re-evaluate every 24-48 hrs Negotiate with patient to ensure compliance

51. Constipation

52. Reduced frequency/increased difficulty –> B.O. Leads to: Malaise Anorexia Abdo discomfort Colic Faecal overflow (‘Diarrhoea’= overflow) Faecal incontinence Nausea & Vomiting Urinary retention Psychological distress

53. Causes of Constipation Debility (Inactivity, inability to go to toilet at right time) Diet (poor oral intake of fluids or food esp fibre) Drugs (Opioids, Antiemetics, Anticholinergics, Diuretics) Disordered Metabolism (Hypercalcaemia, Hypokalaemia, Hypothyroidism) Disease (Cancer) Disordered Neurology (eg Spinal Cord Compression, autonomic neuropathy)

54. To treat Constipation effectively... you need to ask for the gory details!

56. Types 1 – 2 = Constipation Types 3 – 4 = Ideal Stools Types 5 – 7 = Diarrhoea/urgency

57. Treating Constipation When: did they last have their B.O. ? Flatus? What: are their stools like? Hard or Soft? PR? How: often do they usually go? Ie What is their ‘normal’ bowel habit Why: are they constipated? Ie Treat reversible causes (eg ?contributing drugs)

58. Managing Constipation Avoid if possible If stools Hard – Needs softener If stools Soft – Needs stimulant If impacted (not obstructed) consider Movicol PO Patients on reg opioids need reg stimulant If opioid increased: INCREASE laxative! If opioid decreased: DECREASE laxative!

59. Types of Oral Laxatives Stimulants Increase GI motility NB Use with Opioids *Contraindicated in GI obstruction* SENNA Bisacodyl Sodium Picosulphate [Danthron] (Sodium Docusate) Softeners (SODIUM DOCUSATE) [Liquid Paraffin] Osmotic agents ‘MOVICOL’ (Macrogols) Lactulose Magnesium Hydroxide Magnesium Sulphate

60. Types of Oral Laxatives Combination laxatives: Stimulant + Softener Co-danthramer (Danthron + Poloxamer) Co-danthrusate (Danthron + Docusate) Both potentially carcinogenic Reserved for terminal care Beware colours urine red Beware Severe Danthron burns -> severe excoriation esp if any chance of faecal incontinence

61. Types of Oral Laxatives Bulk-forming agents Increase faecal mass & stimulate peristalsis Use in IBS, Diverticular Disease ‘FYBOGEL’ (Ispaghula Husk) Methylcellulose

62. Rectal preparations Suppositories Stimulants Bisacodyl Glycerol Enemas Softeners (Docusate) Arachis Oil (=Peanut) Osmotic agents Phosphate enema Sodium citrate (‘Microlette’, ‘Microlax’)

63. Constipation Summary Avoid if possible (eg starting/increasing Opioids) Remember reversible causes Ask for the gory details! PR really helpful (NB ?overflow) Use appropriate laxative Negotiate with patient to ensure compliance

64. Thank you for surviving this session...... Enjoy your dinner tonight!

65. References Oxford Textbook of Palliative Medicine, Fourth Edition; Eds Geoffrey Hanks, Nathan I. Cherny, Nicholas A. Christakis, Marie Fallon, Stein Kaasa and Russell K. Portenoy; Oxford University Press, November 2009 BNF, British National Formulary 58, September 2009 PCF3: Palliative Care Formulary, 3rd Ed; Twycross RG, Wilcock A; Oxford: Radcliffe Press, 2008