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

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

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

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

8. Caution Diagnose and treat the underlying cause! Diagnose and treat the underlying cause!

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

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

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

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

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

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

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

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

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

18. Diarrhoea

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

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

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

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

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

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

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

26. CONSTIPATION Definition. Definition. As a passage of less frequent, hard or small amount than the individual own normal habit. As a passage of less frequent, hard or small amount than the individual own normal habit. abd. discomfort, distention, straining and diarrhoea esp. elderly abd. discomfort, distention, straining and diarrhoea esp. elderly Causes Causes 1. Low fibre diet commonest 2. Immobility 3. hypotonic colon due to chronic laxative abuse. 4. Slow gut transit time esp in young females 5. Drugs esp. Opioids, Ca B, Antacids, Antimuscarinics. 6. Disease e.g. myxoedema, ca. colon, hypercalcaemia, Parkinson’s disease

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

28. LAXATIVES 1. Stimulant 2. Bulk-forming 3. Faecal softeners 4. Osmotic 5. Bowel cleansing solutions

29. Stimulant laxatives Senna, Dantron, Bisacodyl Senna, Dantron, Bisacodyl MOA: stimulate myenteric plexus MOA: stimulate myenteric plexus enhancing gut motility enhancing gut motility Ind: terminally ill (dantron); bowel preparation Ind: terminally ill (dantron); bowel preparation C/I: intestinal obstruction C/I: intestinal obstruction S/E: abdominal cramps S/E: abdominal cramps atonic colon atonic colon hypokalaemia hypokalaemia dantron carcinogenic in rodents dantron carcinogenic in rodents Not advisable for long term use 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 Glycerol; Liquid Paraffin Soften stools by increasing the intestinal fluid secretion. Soften stools by increasing the intestinal fluid secretion. Glycerol used as suppository in children 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. 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. Semi synthetic disaccharide of fru.& galac. Fermented by bowel bacteria to lactic & acetic acid which act as Fermented by bowel bacteria to lactic & acetic acid which act as 1. Active osmotic acid 2. Lower intestinal PH 3. Inhibit amonia-proucing bacteria Uses : Uses : in treatment of hepatic encephalopathy. in treatment of hepatic encephalopathy. Regular laxative given once a day Regular laxative given once a day

34. Other agents

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

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

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

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

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