GIS24 Drugs Affecting Motility Of GI Tract Flashcards Preview

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Flashcards in GIS24 Drugs Affecting Motility Of GI Tract Deck (11)
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1
Q

6 drugs

A
  1. Antiemetic
  2. Motility stimulants (prokinetics)
  3. Laxatives
  4. Antidiarrhoeal agents
  5. Antispasmodic agents
  6. Drugs for IBS
2
Q

Mechanism of vomiting

A
  1. Pain, repulsive sights and smells, emotional factors
    —> Sensory afferents
    —> ***Higher centres
    —> Vomiting centre —> nerves to somatic and visceral receptors
  2. Motion sickness
    —> Labyrinth (complex structure in inner ear)
    —> Cerebellum (H1 + mACh receptor)
    —> Vomiting centre —> nerves to somatic and visceral receptors
  3. Endogenous toxins, drugs (e.g. chemotherapy)
    —> 1. Blood
    ——> Chemoreceptor trigger zone (CTZ) (D2 + 5HT3 receptor)
    ——> Vomiting centre —> nerves to somatic and visceral receptors
    —> 2. Release of emetogenic agents (5HT, prostanoids, free radicals)
    ——> Visceral afferents / CTZ
  4. Stimulus from pharynx and stomach
    —> Visceral afferents (5HT3)
    —> Nucleus of the solitary tract (5HT3, D2, mACh, H1 receptor) / CTZ
    —> Vomiting centre —> nerves to somatic and visceral receptors
3
Q

Antiemetic

A
  1. H1 receptor antagonist e.g. **Dimenhydrinate
    SE:
    - dizziness, sedation, confusion
    - **
    inhibit muscarinic receptors as well (cause dry mouth, blurred vision, urinary retention, constipation)
  2. Muscarinic receptor antagonist e.g. ***Hyoscine
    SE:
    - drowsiness, dry mouth, blurred vision, urinary retention, constipation, tachycardia
  3. 5HT3 receptor antagonist e.g. ***Ondansetron
    SE:
    - headache, dizziness, constipation
  4. Dopamine receptor antagonist e.g. **Metoclopramide / **Domperidone
    SE:
    - headache, dizziness
    - Metoclopramide blocks dopamine receptors elsewhere in CNS —> ***extrapyramidal symptoms (parkinsonian features, dystonias, tardive dyskinesia)
    - Domperidone does not penetrate BBB (CTZ on blood side of barrier) —> less central SE
4
Q

Control of GI motility

A

Pressure / other stimuli —> ***Enterochromaffin cells (=/ ECL (EC-like)cells!!!!!) —> 5HT

Intrinsic primary afferent nerves (IPAN):
- 5HT1p receptor —> **5HT4 receptor —> ACh, CGRP (calcitonin gene-related peptide) —> ENS neurone —> ACh —> GI muscle wall
- Increase LES tone, stimulation of **
gastric emptying and peristalsis

Extrinsic primary afferent nerves (EPAN):
- **5HT3 receptor —> dorsal root / cranial nerve afferent —> CNS
- **
Nausea, vomiting and abdominal pain
—> Ondansetron (5HT3 antagonist) —> relieve IBS symptoms

5
Q

Motility stimulants (prokinetics)

A

Works via IPAN pathway

  1. 5HT4 receptor agonists e.g. ***Cisapride
    - ↑ release of ACh and CGRP
    —> ↑ LES tone, ↑ gastric emptying and gut motility
    SE:
    - diarrhoea
    - abdominal cramp
    - long QT syndrome —> predisposes to arrhythmia (withdrawn in many countries)
  2. Dopamine D2 receptor antagonists e.g. **Domperidone, Metoclopramide
    - Dopamine an inhibitory neurotransmitter in IPAN
    - **
    ↑ release of ACh from postganglionic cholinergic neurones in GI tract
    —> ↑ LES tone, ↑ gastric emptying and gut motility
6
Q

Motility stimulants (prokinetics) indication

A
  1. Esophageal reflux
    - **incompetence of LES
    - transient LES relaxation
    - **
    delay in gastric emptying
  2. **Gastroparesis (delayed gastric emptying)
    - occurs when **
    vagal nerves are damaged and muscles of stomach and intestines do not work normally

Treatment: Prokinetics (+ gastric acid inhibitor for esophageal reflux)

7
Q

Drugs for treatment of constipation

A
  1. Bulk laxatives
    - ***Methylcellulose
    - increase faecal mass which stimulates peristalsis
    - drink plenty of water so work more efficiently
    - SE: flatulence (bacteria breakdown methylcellulose to produce gas), abdominal distension
  2. Osmotic laxatives
    - ***Lactulose
    - ↑ water in large bowel by drawing fluid from body into bowel / retain fluid administered with
    - SE: flatulence, abdominal distension
  3. Faecal softeners
    - **Docusate sodium, **Glycerol (rectal use), **Liquid paraffin (rectal use)
    - soften stool materials by acting as **
    detergent —> permit water and lipid to penetrate
    - docusate and glycerol also weak stimulant laxative
    - SE: seepage of paraffin, anal irritation after prolonged use
  4. Stimulant laxatives
    - **Bisacodyl, **Senna
    - Bisacodyl: stimulating sensory nerve endings in gut directly
    - Senna: ***anthraquinones released from senna after hydrolysis by bacteria —> anthraquinones stimulate myenteric plexus
    - SE: diarrhoea, abdominal cramp
8
Q

Drugs for treatment of diarrhoea

A
  1. Oral rehydration solution
    - replace electrolyte deficit adequately
    - enhance absorption of water and electrolytes
    - slightly ***hypo-osmolar (<285 mOsm/L) to prevent possible induction of osmotic diarrhoea
    - amount of rehydration depend on size of individual and degree of dehydration
    - generally adequate when person no longer feels thirsty and has normal urine output
    - homemade: 1 teaspoon salt, 8 teaspoon sugar, 1L water
  2. Opioid receptor agonists (anti-diarrhoeal)
    - **Codeine, **Loperamide, **Diphenoxylate
    - stimulate opioid receptor in enteric neurones —> **
    ↓ gut peristalsis —> ↑ colonic transit time —> ↑ faecal water absorption —> ↓ diarrhoea
    - codeine and loperamide have ***antisecretory actions as well
    - SE: drowsiness, dizziness, constipation, paralytic ileus
  3. Kaolin, Pectin (adsorbents)
    - claim to bind toxins and bacteria
    - no good evidence to show effectiveness
9
Q

Drugs for treating bowel spasms (Antispasmodic drugs)

A

Muscarinic receptor antagonist: **Hyoscine
- inhibit muscarinic receptors in intestinal **
smooth muscle cells

  1. inhibit ANS (ACh secreted under basal condition, control ***basal tone + peristalsis)
  2. inhibit Enteric NS (ACh secreted during ***peristalsis)

Overall:
—> relax intestinal smooth muscle (↓ peristalsis + ↓ basal tone)
—> ↓ spasm

SE: constipation, tachycardia, urinary retention, blurred vision, dry mouth, drowsiness

10
Q

Drugs for irritable bowel syndrome

A
  • IBS: idiopathic chronic disorder
  • abdominal discomfort (pain, bloating, distension, nausea)
  • alteration in bowel habits (diarrhoea, constipation, cycle of both)
  • therapies aim at relieving abdominal pain and discomfort
  1. Predominant diarrhoea: opioid agonists (loperamide)
  2. Predominant constipation: bulk laxatives (methylcellulose) / osmotic laxatives (lactulose)
  3. Muscarinic antagonists (hyoscine)
    **4. 5HT3 antagonists (ondansetron)
    - inhibit EPAN —> inhibit **
    unpleasant visceral sensation (nausea, bloating, pain)
11
Q

Summary

A

Antiemetic:
1. H1 receptor antagonist (Dimenhydrinate)
2. mACh receptor antagonist (Hyoscine)
3. 5HT3 receptor antagonist (Ondansetron)
4. Dopamine receptor antagonist (Metoclopramide, Domperidone)

Motility stimulants:
1. 5HT4 receptor agonist (Cisapride)
2. Dopamine receptor antagonist (Domperidone)

Laxatives:
1. Bulk (Methylcellulose)
2. Osmotic (Lactulose)
3. Faecal softener (Docusate sodium, Glycerol, Liquid paraffin)
4. Stimulant (Bisacodyl, Senna)

Antidiarrhoeal:
1. Oral rehydration therapy
2. Opioid receptor agonist (Codeine, Loperamide, Diphenoxylate)
3. Adsorbent (Kaolin, Pectin)

Antispasmodic agents:
1. Muscarinic receptor antagonist (Hyoscine)

Drugs for IBS:
1. 5HT3 receptor antagonist (Ondansetron)