Management of Management of

Common GIT disordersCommon GIT disorders

October 2005October 2005

NAUSEA & VOMITINGNAUSEA & VOMITING

ANTI-EMETIC AGENTSANTI-EMETIC AGENTS

PathophysiologyPathophysiology

Vomiting center (VC) is situated in the brain Vomiting center (VC) is situated in the brain stemstem

Afferent trigger input fibers to the center come Afferent trigger input fibers to the center come from the chemoreceptor trigger zone (CTZ)from the chemoreceptor trigger zone (CTZ)

CTZ in the floor of the 4CTZ in the floor of the 4thth ventricle (outside BBB). ventricle (outside BBB). CTZ receives chemical stimuli from all over the CTZ receives chemical stimuli from all over the

body e.g. gut, medication, toxins, eyes, ears, body e.g. gut, medication, toxins, eyes, ears, nose, pain, cvs (hypotension) .nose, pain, cvs (hypotension) .

Efferent connections activate the vasomotor, Efferent connections activate the vasomotor, respiratory and salivary center in the medulla.respiratory and salivary center in the medulla.

Mechanism of vomitingMechanism of vomiting

Chemical transmitters includeChemical transmitters include

Histamine (H1)Histamine (H1)

Acetylcholine (muscarinic)Acetylcholine (muscarinic)

Dopamine (D2)Dopamine (D2)

5-hydroxytryptamine (5HT3) 5-hydroxytryptamine (5HT3)

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Emetic drugsEmetic drugs

IpecacuanhaIpecacuanha Local action in stomachLocal action in stomach Alkaloids (emetine; cephaeline)Alkaloids (emetine; cephaeline) Not if impaired consciousnessNot if impaired consciousness Not if corrosive substances Not if corrosive substances

ingestedingested Limited useLimited use

Antiemetic drugsAntiemetic drugs

AntihistaminesAntihistamines AntimuscarinicsAntimuscarinics Dopamine receptor antagonistsDopamine receptor antagonists 5 hydroxytryptamine antagonists5 hydroxytryptamine antagonists CannabinoidsCannabinoids CorticosteroidsCorticosteroids

CautionCaution

Diagnose and treat the underlying Diagnose and treat the underlying cause!cause!

AntihistaminesAntihistamines

Eg promethazine (sedative); Eg promethazine (sedative); cinnarizine (non-sedative)cinnarizine (non-sedative)

H1 receptor antagonistsH1 receptor antagonists Useful for motion sickness; Useful for motion sickness;

vestibularvestibular No effect on CTZNo effect on CTZ S/E drowsinessS/E drowsiness Caution re:driving and alcoholCaution re:driving and alcohol

Important interactionImportant interaction

Terfenadine (antihistamine)Terfenadine (antihistamine) Cyt P450 3ACyt P450 3A Grapefruit juice; macrolide Grapefruit juice; macrolide

antibioticsantibiotics Increased plasma levelsIncreased plasma levels Life threatening arrhythmiasLife threatening arrhythmias

AntimuscarinicAntimuscarinic

Eg hyoscineEg hyoscine Used for motion sickness; pre-opUsed for motion sickness; pre-op Do not act on CTZDo not act on CTZ Oral or patch availableOral or patch available S/E drowsiness; dry mouth; S/E drowsiness; dry mouth;

urinary retention; dizzinessurinary retention; dizziness

Dopamine receptor Dopamine receptor antagonistsantagonists

Phenothiazines & butyrophenonesPhenothiazines & butyrophenones Prochlorperazine (stemetil)Prochlorperazine (stemetil) D2 receptor antagonistsD2 receptor antagonists Some antihistamine and Some antihistamine and

atimuscarinicatimuscarinic Effective on CTZEffective on CTZ S/E sedation; extrapyramidal; S/E sedation; extrapyramidal;

antimuscarinic; raised prolactinantimuscarinic; raised prolactin

Dopamine receptor Dopamine receptor antagonistsantagonists

MetoclopramideMetoclopramide Domperidone (does not cross the Domperidone (does not cross the

BBB)BBB) D2 receptor antagonistsD2 receptor antagonists Effective on CTZEffective on CTZ S/E acute dystonic reactions; S/E acute dystonic reactions;

oculogyric crisis; spasmodic torticollisoculogyric crisis; spasmodic torticollis Especially in youngEspecially in young

5 HT3 antagonists5 HT3 antagonists

Eg ondansetron; dolansetronEg ondansetron; dolansetron Effective on CTZ and gutEffective on CTZ and gut Used in chemo and radiotherapy Used in chemo and radiotherapy

associated nausea & vomitingassociated nausea & vomiting S/E headache; constipation; S/E headache; constipation;

flushing; transient rise LFTsflushing; transient rise LFTs

CannabinoidsCannabinoids

Eg nabiloneEg nabilone Acts on opioid receptorsActs on opioid receptors Effective on CTZEffective on CTZ Used in chemotherapy assoc. Used in chemotherapy assoc.

nauseanausea S/E hallucinations; psychotic S/E hallucinations; psychotic

reactions; sleep disturbance; reactions; sleep disturbance; ataxiaataxia

CorticosteroidsCorticosteroids

Eg methylprednisolone; Eg methylprednisolone; dexamethasonedexamethasone

Weak antiemetic effectWeak antiemetic effect Uncertain MOAUncertain MOA Used in combination with 5HT3 Used in combination with 5HT3

antagonistsantagonists Chemotherapy; raised IC pressureChemotherapy; raised IC pressure

Vomiting of pregnancyVomiting of pregnancy

Usually self-limitingUsually self-limiting Promethazine safePromethazine safe Prochlorperazine; Prochlorperazine;

metoclopramidemetoclopramide Hyperemesis requires specialist Hyperemesis requires specialist

referralreferral

DiarrhoeaDiarrhoea

DiarrhoeaDiarrhoea

Frequent passage of liquid faecesFrequent passage of liquid faeces AcuteAcute

- infections (viral;bacterial;parasitic)- infections (viral;bacterial;parasitic)

- drugs (Mg2+;cytotoxics)- drugs (Mg2+;cytotoxics)

- antibiotic associated (c. difficile)- antibiotic associated (c. difficile) ChronicChronic

- usually non - usually non infectious( IBD;IBS;CA;Coeliac)infectious( IBD;IBS;CA;Coeliac)

- need to investigate the cause- need to investigate the cause

Acute diarrhoeaAcute diarrhoea

gut motility gut motility secretions secretions absorptionabsorption

Electrolyte depletion & water lossElectrolyte depletion & water loss Rehydration is priorityRehydration is priority

Maintaining electrolyte Maintaining electrolyte balancebalance

Often Often fluid intake sufficientfluid intake sufficient Na and glucose co-transport in Na and glucose co-transport in

gutgut Glucose enhances absorption of Glucose enhances absorption of

NaNa Eg DioralyteEg Dioralyte

Anti-infective agentsAnti-infective agents

Usually not necessaryUsually not necessary Severe campylobacter – Severe campylobacter –

erythromycin; ciprofloxacinerythromycin; ciprofloxacin Typhoid; amoebic dysentery; Typhoid; amoebic dysentery;

choleracholera Occasionally ciprofloxacin as Occasionally ciprofloxacin as

prophylaxis for traveller’s prophylaxis for traveller’s diarrhoeadiarrhoea

Antibiotic associated Antibiotic associated diarrhoeadiarrhoea

Overgrowth of C. difficileOvergrowth of C. difficile Pseudomembranous colitisPseudomembranous colitis Toxic megacolonToxic megacolon Treat with oral metronidazoleTreat with oral metronidazole Oral vancomycin alternativeOral vancomycin alternative Or IV metronidazoleOr IV metronidazole Sensible use of antibioticsSensible use of antibiotics

Antidiarrhoeal drugsAntidiarrhoeal drugs

Opioids & antimuscarinics Opioids & antimuscarinics Eg codeineEg codeine loperamide;diphenoxylate loperamide;diphenoxylate

(do not pass BBB)(do not pass BBB) Antimotility & antisecretoryAntimotility & antisecretory

CautionsCautions

Young children – perecipitate Young children – perecipitate ileusileus

Bacillic dysentery – prolong Bacillic dysentery – prolong infectioninfection

IBD – precipitate toxic mega colonIBD – precipitate toxic mega colon

CONSTIPATIONCONSTIPATION Definition . Definition . As a passage of less frequent, hard or small As a passage of less frequent, hard or small

amount than the individual own normal habit .amount than the individual own normal habit . abd. discomfort , distention, straining and abd. discomfort , distention, straining and

diarrhoea esp. elderlydiarrhoea esp. elderly

Causes Causes 1.1. Low fibre diet commonest Low fibre diet commonest 2.2. Immobility Immobility 3.3. hypotonic colon due to chronic laxative abuse. hypotonic colon due to chronic laxative abuse. 4.4. Slow gut transit time esp in young femalesSlow gut transit time esp in young females5.5. Drugs esp. Opioids, Ca B, Antacids, Drugs esp. Opioids, Ca B, Antacids,

Antimuscarinics.Antimuscarinics.6.6. Disease e.g. myxoedema, ca. colon, Disease e.g. myxoedema, ca. colon,

hypercalcaemia, Parkinson’s diseasehypercalcaemia, Parkinson’s disease

Before prescribingBefore prescribing

Confirm diagnosis of constipationConfirm diagnosis of constipation

Rule out underlying organic Rule out underlying organic

causescauses

Rule out intestinal obstructionRule out intestinal obstruction

LAXATIVESLAXATIVES

1.1. Stimulant Stimulant

2.2. Bulk-forming Bulk-forming

3.3. Faecal softeners Faecal softeners

4.4. Osmotic Osmotic

5.5. Bowel cleansing solutions Bowel cleansing solutions

Stimulant laxativesStimulant laxatives

Senna, Dantron, BisacodylSenna, Dantron, Bisacodyl MOA: MOA: stimulate myenteric plexus stimulate myenteric plexus

enhancing gut motility enhancing gut motility Ind: terminally ill (dantron); bowel preparationInd: terminally ill (dantron); bowel preparation

C/I: intestinal obstructionC/I: intestinal obstruction S/E: abdominal crampsS/E: abdominal cramps

atonic colonatonic colon

hypokalaemiahypokalaemia

dantron carcinogenic in rodentsdantron carcinogenic in rodents Not advisable for long term useNot advisable for long term use

Bulk forming laxativesBulk forming laxatives

Bran, Sterculia, Methylcellulose; ispaghulaBran, Sterculia, Methylcellulose; ispaghula

MOA: increase faecal mass stimulating peristalsisMOA: increase faecal mass stimulating peristalsis

Ind: constipationInd: constipation

C/I: intestinal obstruction; faecal impactionC/I: intestinal obstruction; faecal impaction

S/E: intestinal obstruction (ensure adequate S/E: intestinal obstruction (ensure adequate fluids)fluids)

Good for long term treatment provided adequate Good for long term treatment provided adequate fluidfluid

Faecal SoftenersFaecal Softeners

Glycerol; Liquid ParaffinGlycerol; Liquid Paraffin Soften stools by increasing the Soften stools by increasing the

intestinal fluid secretion .intestinal fluid secretion . Glycerol used as suppository in Glycerol used as suppository in

children children L. Paraffin orally but rarely used L. Paraffin orally but rarely used

because it prevent absorption of fat s. because it prevent absorption of fat s. vitamins & accidental inhalation cause vitamins & accidental inhalation cause lipoid pneumonia. lipoid pneumonia.

Osmotic laxativesOsmotic laxatives

Lactulose; Macrogols; Magnesium salts; phosphate Lactulose; Macrogols; Magnesium salts; phosphate enemaenema

MOA: MOA: poorly absorbed causing osmotic increase of luminal poorly absorbed causing osmotic increase of luminal intestinal fluid intestinal fluid

Ind: constipation; hepatic encephalopathy Ind: constipation; hepatic encephalopathy (lactulose)(lactulose)

C/I: intestinal obstruction; renal failure (Mg2+ salts)C/I: intestinal obstruction; renal failure (Mg2+ salts)

S/E: abdominal cramps; dehydrationS/E: abdominal cramps; dehydration

Lactulose Lactulose

Semi synthetic disaccharide of fru.& Semi synthetic disaccharide of fru.& galac. galac.

Fermented by bowel bacteria to lactic & Fermented by bowel bacteria to lactic & acetic acid which act as acetic acid which act as

1.1. Active osmotic acid Active osmotic acid 2.2. Lower intestinal PHLower intestinal PH3.3. Inhibit amonia-proucing bacteria Inhibit amonia-proucing bacteria UsesUses : : in treatment of hepatic encephalopathy.in treatment of hepatic encephalopathy. Regular laxative given once a dayRegular laxative given once a day

Other agentsOther agents

AntispasmodicsAntispasmodics

1 Muscarinic antagonists1 Muscarinic antagonists Eg hyoscine Eg hyoscine

(buscopan);propantheline(buscopan);propantheline S/E anticholinergicS/E anticholinergic 2 Direct relaxants2 Direct relaxants Eg mebeverine; peppermint oilEg mebeverine; peppermint oil

Motility stimulantsMotility stimulants

Metoclopramide; domperidoneMetoclopramide; domperidone Speed gastric emptying and small Speed gastric emptying and small

intestinal transitintestinal transit Used for non-ulcer dyspepsia; Used for non-ulcer dyspepsia;

gastro-oesophageal refluxgastro-oesophageal reflux

Irritable bowel Irritable bowel syndromesyndrome High fibreHigh fibre ReassuranceReassurance LaxativesLaxatives Antidiarrhoeals (avoid codeine)Antidiarrhoeals (avoid codeine) AntispasmodicsAntispasmodics

Diverticular diseaseDiverticular disease

High fibreHigh fibre Bulking agentsBulking agents AntispasmodicsAntispasmodics Antibiotics for acute diverticulitisAntibiotics for acute diverticulitis Antimotility agents Antimotility agents

contraindicatedcontraindicated

Haemorrhoids & anal Haemorrhoids & anal fissurefissure

Dietary adviceDietary advice Bulk-forming laxativesBulk-forming laxatives Local anaesthetics eg lignocaineLocal anaesthetics eg lignocaine s/e stinging skin sensitivitys/e stinging skin sensitivity Topical corticosteroidsTopical corticosteroids Sclerosants eg phenolSclerosants eg phenol