Pharmacology Of Gi System Notes

Lecture 5

Pharmacology of GI system

LECTURE 1

• Nausea and vomiting

  • ANTI-EMETICS

    • General

      • Act centrally to inhibit or prevent emesis

      • Include antagonists of

        • D₂ receptor (chemical trigger zone)

        • 5-HT receptor (chemical trigger zone)

        • H1-receptor (NTS)

        • AChM receptor (vomiting centre)

    • Types

      • D₂ Dopamine receptor antagonists

        • Phenothiazines- CHLORPROMAZINE & ACEPROMAZINE

          • General

            • Good at preventing vomiting agents directly stimulating CTZ

            • Sedative action= more useful for motion sickness

            • Also antagonises H1 and AChM receptors (dirty)

          • Side effects

            • Hypotension, platelet dysfunction, ataxia

            • Not recommended for pregnant, affects babies (+500mg)

        • METACLOPRAMIDE

          • General

            • Blocks 5-HT3 receptors= large part of effect

            • Peripheral actions- increased muscle tone in lower oesophageal sphincter (near stomach) to prevent vomiting

          • Side effects

            • As chlorpromazine, Diarrhoea

      • 5-HT receptor antagonists

        • ONDANSETRON

          • Particularly useful in chemo/radiotherapy

          • Side effects: drowsiness & dizziness

        • NABILONE

          • Synthetic cannabinoid (not first choice- addiction)

          • Used in cytotoxic-induced vomiting

          • Side effect: drowsiness & dizziness

      • 5-HT4 receptor agonists

        • CISAPRIDE

          • General

            • Peripherally, increasing gastro-oesophageal sphincter contraction & GI motility

            • Withdrawn= long QT-syndrome (death)

          • Side effects (high dosage)

            • Diarrhoea, abdominal cramp

      • Corticosteroids

        • DEXAMTHASONE

          • Operation or surgically induced vomiting

          • Mechanisms (maybe)

            • CTZ and Visceral afferents antagonist

            • Decreasing prostaglandin activity on brain

            • Increase endorphin release

            • Potentiating effects of other anti-emetics

          • Clinical use

            • Against moderately emetogenic chemo

            • Combo with others (5HT3 antagonists) against highly emetogenic chemo & preventing post operative nausea/vomiting

      • H1 histamine receptor antagonists

        • DIPHENHYDRAMINE, CYCLIZINE, PREMETHAZINE

          • General

            • Purely central action

            • Highly effective for motion sickness & against stimuli acting locally in stomach

            • Dirty- anti-muscarinic activity

          • Side effects

            • Drowsiness, sedation

      • Muscarinic Ach blockers

        • HYOSCINE (SCOPOLAMINE)

          • General

            • Effective against motion sickness

            • Not against substances stimulating CTZ

          • Side effects

            • Anti-muscarinic

            • Drowsiness, blurred vision, dry mouth, urine retention

  • PRO-KINETIC DRUGS

    • General

      • More content out of stomach, faster

      • Decreases pressure in stomach

    • Types

      • D2 antagonists

        • DOMEPERIDONE, METACLOPRAMIDE

          • D2 decreases gastric emptying

          • Drugs inhibit this

      • Motilin agonists

        • ERYTHROMYCIN

          • Motilin increases gastric emptying

          • Drug promotes this

      • 5HT4 agonists

        • CISAPRIDE

          • 5HT4 increases gastric motility

          • Drug promotes this

      • M3+ antagonists

        • BETHANECOL

          • M3+ decreases gastric emptying

          • Drug inhibits this

  • EMETICS

    • IPECACUANHA

      • Active constituents= alkaloids emetine & cephaline

      • Irritant to stomach lining

    • APOMORPHINE

      • D2 dopamine agonist (centrally in CTZ)

    • WASHING SODA (NA2CO3), SALT, MUSTARD

• Diarrhoea

  • Principles of treating

    • Symptomatic

      • Correct fluid/electrolyte loss, food withdrawal

    • Antibiotics

    • Absorbents

      • Charcoal, Kaolin, Pectin, Bismuth salts

      • Absorb micro organisms and toxins

      • Overall value doubtful

    • Drugs

      • CFTR channel blocker: CROFELEMER

        • Entero-toxins cause longer opening and increased Cl- secretion & thus water secretion

        • Drug decreases both Cl- secretion and H2O secretion

      • Motility-modifying drugs

        • ANTI-MUSCARINICS

          • Little use

          • Reduce peristalsis and segmental contractions

          • Might be used in short term for pain relief

          • Can cause constipation & increased H2O absorption

        • OPIODS

          • Reduce peristalsis but increase segmental contractions, direct effect on µ receptor on GI SM

          • Some also increase fluid & water absorption

          • Side effects: Nausea, vomiting, constipation

      • Anti-inflammatories: SULPHASALAZINE

        • Treat IBD and severe UC

      • Corticosteroids: PREDNISOLONE, DEXAMETHAZONE

• Constipation

  • Laxatives

    • Accelerate passage of contents through intestines

      • Lubricants

        • LIQUID PARAFFIN

          • Lubricates contents of tract to promote movement

          • Generally safe

          • Side effects: Could affect absorption of things

      • Bulk-forming drugs

        • STERCULIA, BRAN

          • Increase volume of non absorbable food in colon

          • If constipation caused by blockage=DANGEROUS

          • Side effects: Possible dehydration

      • Intestinal stimulants

        • BISACODYL, DANTRON, PHENOLPHTHALEIN

          • Stimulate contraction of intestine

          • Stimulate cAMP, cholecystokinin & vasoactive intestinal peptide synthesis

    • Reduce water absorption

      • Osmotic laxatives

        • MgSO4, LACTULOSE

          • Poorly absorbed solutes in GI tract, promote water movement into lumen

LECTURE 2

• Gastric Ulceration

  • Regulation of...

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