1. Management of Common GIT disorders October 2005

2. NAUSEA & VOMITING ANTI-EMETIC AGENTS

3. Pathophysiology • Vomiting center (VC) is situated in the brain stem • Afferent trigger input fibers to the center come from the chemoreceptor trigger zone (CTZ) • CTZ in the floor of the 4th ventricle (outside BBB). • CTZ receives chemical stimuli from all over the body e.g. gut, medication, toxins, eyes, ears, nose, pain, cvs (hypotension) . • Efferent connections activate the vasomotor, respiratory and salivary center in the medulla.

4. Mechanism of vomiting Chemical transmitters include Histamine (H1) Acetylcholine (muscarinic) Dopamine (D2) 5-hydroxytryptamine (5HT3)

5. Downloaded from: StudentConsult (on 17 October 2005 11:12 AM) © 2005 Elsevier

6. Emetic drugs • Ipecacuanha • Local action in stomach • Alkaloids (emetine; cephaeline) • Not if impaired consciousness • Not if corrosive substances ingested • Limited use

7. Antiemetic drugs • Antihistamines • Antimuscarinics • Dopamine receptor antagonists • 5 hydroxytryptamine antagonists • Cannabinoids • Corticosteroids

8. Caution • Diagnose and treat the underlying cause!

9. Antihistamines • Eg promethazine (sedative); cinnarizine (non-sedative) • H1 receptor antagonists • Useful for motion sickness; vestibular • No effect on CTZ • S/E drowsiness • Caution re:driving and alcohol

10. Important interaction • Terfenadine (antihistamine) • Cyt P450 3A • Grapefruit juice; macrolide antibiotics • Increased plasma levels • Life threatening arrhythmias

11. Antimuscarinic • Eg hyoscine • Used for motion sickness; pre-op • Do not act on CTZ • Oral or patch available • S/E drowsiness; dry mouth; urinary retention; dizziness

12. Dopamine receptor antagonists • Phenothiazines & butyrophenones • Prochlorperazine (stemetil) • D2 receptor antagonists • Some antihistamine and atimuscarinic • Effective on CTZ • S/E sedation; extrapyramidal; antimuscarinic; raised prolactin

13. Dopamine receptor antagonists • Metoclopramide • Domperidone (does not cross the BBB) • D2 receptor antagonists • Effective on CTZ • S/E acute dystonic reactions; oculogyric crisis; spasmodic torticollis • Especially in young

14. 5 HT3 antagonists • Eg ondansetron; dolansetron • Effective on CTZ and gut • Used in chemo and radiotherapy associated nausea & vomiting • S/E headache; constipation; flushing; transient rise LFTs

15. Cannabinoids • Eg nabilone • Acts on opioid receptors • Effective on CTZ • Used in chemotherapy assoc. nausea • S/E hallucinations; psychotic reactions; sleep disturbance; ataxia

16. Corticosteroids • Eg methylprednisolone; dexamethasone • Weak antiemetic effect • Uncertain MOA • Used in combination with 5HT3 antagonists • Chemotherapy; raised IC pressure

17. Vomiting of pregnancy • Usually self-limiting • Promethazine safe • Prochlorperazine; metoclopramide • Hyperemesis requires specialist referral

18. Diarrhoea

19. Diarrhoea • Frequent passage of liquid faeces • Acute - infections (viral;bacterial;parasitic) - drugs (Mg2+;cytotoxics) - antibiotic associated (c. difficile) • Chronic - usually non infectious( IBD;IBS;CA;Coeliac) - need to investigate the cause

20. Acute diarrhoea • gut motility secretions absorption • Electrolyte depletion & water loss • Rehydration is priority

21. Maintaining electrolyte balance • Often fluid intake sufficient • Na and glucose co-transport in gut • Glucose enhances absorption of Na • Eg Dioralyte

22. Anti-infective agents • Usually not necessary • Severe campylobacter – erythromycin; ciprofloxacin • Typhoid; amoebic dysentery; cholera • Occasionally ciprofloxacin as prophylaxis for traveller’s diarrhoea

23. Antibiotic associated diarrhoea • Overgrowth of C. difficile • Pseudomembranous colitis • Toxic megacolon • Treat with oral metronidazole • Oral vancomycin alternative • Or IV metronidazole • Sensible use of antibiotics

24. Antidiarrhoeal drugs • Opioids & antimuscarinics • Eg codeine • loperamide;diphenoxylate (do not pass BBB) • Antimotility & antisecretory

25. Cautions • Young children – perecipitate ileus • Bacillic dysentery – prolong infection • IBD – precipitate toxic mega colon

26. CONSTIPATION • Definition . • As a passage of less frequent, hard or small amount than the individual own normal habit . • abd. discomfort , distention, straining and diarrhoea esp. elderly • Causes • Low fibre diet commonest • Immobility • hypotonic colon due to chronic laxative abuse. • Slow gut transit time esp in young females • Drugs esp. Opioids, Ca B, Antacids, Antimuscarinics. • Disease e.g. myxoedema, ca. colon, hypercalcaemia, Parkinson’s disease

27. Before prescribing • Confirm diagnosis of constipation • Rule out underlying organic causes • Rule out intestinal obstruction

28. LAXATIVES • Stimulant • Bulk-forming • Faecal softeners • Osmotic • Bowel cleansing solutions

29. Stimulant laxatives • Senna, Dantron, Bisacodyl • MOA: stimulate myenteric plexus enhancing gut motility • Ind: terminally ill (dantron); bowel preparation • C/I: intestinal obstruction • S/E: abdominal cramps atonic colon hypokalaemia dantron carcinogenic in rodents • Not advisable for long term use

30. Bulk forming laxatives Bran, Sterculia, Methylcellulose; ispaghula MOA: increase faecal mass stimulating peristalsis Ind: constipation C/I: intestinal obstruction; faecal impaction S/E: intestinal obstruction (ensure adequate fluids) Good for long term treatment provided adequate fluid

31. Faecal Softeners • Glycerol; Liquid Paraffin • Soften stools by increasing the intestinal fluid secretion . • Glycerol used as suppository in children • L. Paraffin orally but rarely used because it prevent absorption of fat s. vitamins & accidental inhalation cause lipoid pneumonia.

32. Osmotic laxatives Lactulose; Macrogols; Magnesium salts; phosphate enema MOA: poorly absorbed causing osmotic increase of luminal intestinal fluid Ind: constipation; hepatic encephalopathy (lactulose) C/I: intestinal obstruction; renal failure (Mg2+ salts) S/E: abdominal cramps; dehydration

33. Lactulose • Semi synthetic disaccharide of fru.& galac. • Fermented by bowel bacteria to lactic & acetic acid which act as • Active osmotic acid • Lower intestinal PH • Inhibit amonia-proucing bacteria Uses : • in treatment of hepatic encephalopathy. • Regular laxative given once a day

34. Other agents

35. Antispasmodics • 1 Muscarinic antagonists • Eg hyoscine (buscopan);propantheline • S/E anticholinergic • 2 Direct relaxants • Eg mebeverine; peppermint oil

36. Motility stimulants • Metoclopramide; domperidone • Speed gastric emptying and small intestinal transit • Used for non-ulcer dyspepsia; gastro-oesophageal reflux

37. Irritable bowel syndrome • High fibre • Reassurance • Laxatives • Antidiarrhoeals (avoid codeine) • Antispasmodics

38. Diverticular disease • High fibre • Bulking agents • Antispasmodics • Antibiotics for acute diverticulitis • Antimotility agents contraindicated

39. Haemorrhoids & anal fissure • Dietary advice • Bulk-forming laxatives • Local anaesthetics eg lignocaine • s/e stinging skin sensitivity • Topical corticosteroids • Sclerosants eg phenol