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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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