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)
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
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
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
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