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Drugs used in GI disorders
Dr. Khairun Nain
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Learning outcomes
Common causes of constipation &diarrhoea
Drugs that increase GI motility
Drugs that decrease GI motility
Drugs that relieve nausea & vomiting
Mechanisms of action and commonadverse effects
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CONSTIPATION AND
DIARRHOEA
Drugs affecting motility
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GI MOTILITY
Myogenic
Intrinsic rhythmicity
Hormonal Endocrine & paracrine
Hormones released due to nervous stimulation,distention, chemical stimulation
Neuronal
Extrinsic sympathetic and parasympathetic
Intrinsic
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Recap of gut motility
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CONSTIPATION
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Constipation
Infrequent BO/hard stools/difficulty passing General causes:
Inadequate fibre/ high in red meat Dehydration Lack of activity
Specific causes: Drugs opioids, tricyclics, anticonvulsants, CCBs,
excessive laxatives Hormones hypothyroidism, pregnancy etc PathologyCa colon, Hirschsprungs, DM, IBS/IBD
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Drugs for Constipation
Purgatives/Laxatives
Bulk & osmotic laxatives
Faecal softeners
Stimulant laxatives
Drugs than increase motility/Prokinetics
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Bulk Laxatives
Methycellulose, sterculia, agar, bran,ispaghula husk, psylium, polycarbophil
Plant fibres
Undigestible, absorbs water
Stretches and promotes
peristalsis
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Osmotic laxatives
Soluble but unabsorbable increasedstool liquidity
Lactulose, sorbitol nonabsorbable sugars Magnesium oxide, MgOH should be
avoided in poor renal function and
children => hypermagnesaemia Purgatives/bowel prep Mg citrate,
sodium phosphate, PEG
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Faecal softeners
Soften stool by acting as a detergentmixing of lipid and water
Docusate
Glycerin supp
Arachis/mineral oil
Liquid paraffin
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Stimulant laxatives
Mech
Increase electrolyte and water secretion
Direct stimulation of enteric nerves & peristalsis Cramping & dependency
Bisacodyl PO/supp
Glycerol supp
Aloe, senna, cascara, castor oil and dantronplant based stimulants
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Diarrhoea
1.5 million child deaths due to diarrhoea
Rehydrate.org
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Diarrhoea
Frequent passage of liquid faeces Physiology
Increased motility Increased secretion Decreased absorption
Common Causes Infection and toxins Underlying disease IBD/IBS Drugs/radiation Psychological
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Antidiarrhoeals
Antimotility and spasmolytics
Opioid agonists
Colloidal bismuth compounds
Octreotide inhibition of endocrine tumours
Adsorbents
Kaolin & Pectin
Bile salt-binding resins
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Opioids
Well-known constipator
Complex mechanism
CNS penetration &
dependency
Diphenoxylate
Loperamide
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Adsorbents
Kaolin
Hydrated magnesium aluminium silicate
Pectin
Indigestible carbohydrate
Binds bacteria, toxins and possibly coating
intestinal mucosa
Chalk, charcoal, etc
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NAUSEA & VOMITING
ANTI-EMETICS
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Nausea & Vomiting
Forced evacuation of gastric contentsthrough the mouth
Nausea feeling of impending vomiting
Retching repetitive contraction of abdomuscles with or without discharge
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Anti-emetics
Serotonin 5-HT3 antagonists
H1-receptor antagonists
Muscarinic antagonists
D2-receptor antagonists
Cannabinoids
Corticosteroids
Neurokinin-1 antagonists
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Serotonin 5-HT3 antagonists
Blocks serotonin receptors at CTZ and vomitingcentre
Blocks extrinsic vagal and afferent nerves Effective for emesis due to vagal stimulation
post-operative post-chemotherapy post-radiation
Ondansetron, granisetron, dolasetron,palonosetron
Can be given PO/IV
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Serotonin 5-HT3 antagonists
Half life 4-9 hours, palonosetron 40 hrs
Well-tolerated, mild QT-prolongation
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H1-receptor antagonists
Weak anti-emetic but useful in motionsickness
Diphenhydramine,dimenhydrinate,
meclizine
AEs: dizziness, sedation, confusion, dry
mouth, cycloplegia, urinary retention
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Muscarinic antagonists
Hyoscine (scopolamine) is the prototype
Widely used for motion sickness
Anticholinergic effects: dry mouth, blurredvision
Drowsiness
PO or transdermal patch
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Cannabinoids
Nabilone ,Dronabinol Tetrahydrocannabinoids Mech unknown Appetite stimulant AEs: euphoria,dysphoria
sedation,hallucinations
dry mouth Autonomictachycardia,conjunctival
injection,orthostatic hypotension
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Corticosteroids
Dexamethasone PO or IV
Unknown mechanism
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Neurokinin-1 antagonists
Aprepitant
Blockade at CNS area postrema
Used in combination with serotonin 5HT3antagonists and corticosteroids inchemotherapy
Metabolised via CYP3A4 pathwayAEs: fatigue, dizziness, diarrhea
Given PO, bioavailability ~ 65%
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Other anti-emetics
Antipsychotics
Phenothiazines: prochlorperazine,
promethazine, thiethylperazine Droperidol (fatal QT-prolongation)
Benzodiazepines
Lorazepam/diazepam
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