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17. Clinical Pharmacology and Therapeutics > 24. Drugs Affecting Gut Motility > Flashcards

24. Drugs Affecting Gut Motility Flashcards

1
Q

How is gastric motility controlled?

A

Myogenically, neuronally, and hormonally.

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2
Q

What is meant by myogenic control of gastric motility?

A

Rhythmic contraction (slow waves of depolarisation through smooth muscle), passive currents through gap junctions, driven by interstitial cells of Cajal that act as pacemakers of electrical activity.

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3
Q

What is meant by neural control of gastric motility?

A

Intrinsic and extrinsic control, stimulation of post-ganglionic cholinergic enteric nerves -> increase force of gut contraction vs stimulation of non-adrenergic inhibitory nerves -> inhibits contraction.

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4
Q

What are the networks making up the neuronal supply for gastric motility?

A

Local nerves - enteric nervous system, Auerbach’s plexus - between circular and longitudinal layers of muscles, Meissner’s plexus - in submucosa, Henle’s plexus - in circular muscle adjacent to submucosa, Cajal’s plexus - in circular muscle adjacent to longitudinal muscle.

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5
Q

What is the intestine-intestinal inhibitory reflex?

A

Distension of one intestinal segment causes complete intestinal inhibition.

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6
Q

What is the anointestinal inhibitory reflex?

A

Distension of the anus causes intestinal inhibition.

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7
Q

What are the gastrocolic and duodenocolic reflexes?

A

Stimulation of motility after material has entered the stomach or duodenum.

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8
Q

What happens in emesis to the anatomy of the GI tract?

A

The pyloric sphincter closes while cardia and oesophagus relax, gastric contents are propelled by contraction of abdominal wall and diaphragm, glottis closes with elevation of the soft palate to prevent entry of vomit into trachea and nasopharynx.

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9
Q

What are the control centres and neurotransmitters involved in emesis?

A

Vestibular apparatus - ACh, H1; medullary centre - ACh, H1, 5-hydroxytyptamine (5-HT3); postrema on the floor of the 4th ventricle - dopamine.

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10
Q

Name three dopamine D2 receptor antagonists.

A

Domperidone, metoclopramide, phenothiazines.

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11
Q

Name two 5-HT3-receptor antagonists.

A

Ondansetron and granisteron.

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12
Q

Name an anti-muscarinic.

A

Hyoscine.

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13
Q

Name two histamine H1 receptor antagonists.

A

Cyclizine, promethazine.

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14
Q

Name a cannabinoid used in anti-emesis.

A

Nabilone.

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15
Q

Name a benzodiazapine used in anti-emesis.

A

Lorazepam.

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16
Q

What is the action of domperidone, the D2 antagonist?

A

Acts on postrema on the floor of the 4th ventricle and on stomach to increase rate of gastric emptying.

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17
Q

What are the indications for domperidone use?

A

Acute nausea/vomiting.

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18
Q

What are the ADRs of domperidone?

A

Stimulates prolacting release, rarely dystonia.

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19
Q

What is the route of administration of domperidone?

A

Oral or PR.

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20
Q

What is the action of ondansteron, the 5-HT3 antagonist?

A

5-HT into the gut causes vagal stimulation, 5HT3 antagonists work on the postrema on the floor of the 4th ventricle and against the vagal afferent nerves in GI.

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21
Q

What are the indications for ondansteron use?

A

High doses in radiation sickness and chemotherapy, post-operative.

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22
Q

What is the route of administration for ondansteron?

A

IV, IM, or orally.

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23
Q

How can the anti-emetic effect of ondansteron be enhanced?

A

A single dose of corticosteroid.

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24
Q

What are the ADRs of ondansteron?

A

Headaches, constipation, flushing.

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25
Q

What are the actions of metoclopramide?

A

D2 antagonism acting on 4th ventricle and gastric emptying, anti-cholinergic effects, and blocks vagal afferent 5-HT3R.

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26
Q

What are the indications for use of metoclopramide?

A

GI cause for N&V, migraine, post-op.

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27
Q

What are the routes of administration of metoclopramide?

A

Oral, IM, IV.

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28
Q

What is the half life of metoclopramide?

A

4hrs, short.

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29
Q

What are the ADRs of metoclopramide?

A

Extra-pyramidal reactions (dystonia) in 1%, galactorrhoea.

30
Q

What is the action of hyoscine?

A

ACh antagonists via muscarinic cholinergic receptors.

31
Q

What are the indications of use for hyoscine?

A

Motion sickness.

32
Q

What are the routes of administration of hyoscine?

A

Oral or patch.

33
Q

What are the ADRs of hyoscine?

A

Systemic anti-cholinergic effects, bradycardia.

34
Q

What are the actions of cyclizine?

A

H1 antagonism also anti-muscarinic effects.

35
Q

What is the indication of use of cyclizine?

A

Acute nausea and vomiting.

36
Q

What are the routes of administration of cyclizine?

A

Oral, IV, or IM.

37
Q

What are the ADRs of cyclizine?

A

QT prolongation so contraindicated in myocardial ischaemia. Also crosses BBB so sedative effect.

38
Q

What are the five types of laxative?

A

Non-pharmacological, bulk, faecal softeners, osmotic, irritant/stimulants.

39
Q

What are the non-pharmacological approaches to treating constipation?

A

Underlying medical cause, increase fluid intake, high fibre diet, exercise.

40
Q

What are bulk laxatives?

A

Insoluble and non-absorbable substance which distend the gut.

41
Q

How long do bulk laxatives take to work?

A

A few days.

42
Q

What is an ADR of bulk laxatives?

A

Flatulence.

43
Q

What are the CI of bulk laxatives?

A

Adhesions/ulceration as it may cause intestinal obstruction.

44
Q

How do faecal softeners work?

A

Lubricate and soften stool.

45
Q

What are the indications for use of faecal softeners?

A

Constipation, including with adhesions and anal fissures/haemorrhoids.

46
Q

How do magnesium and sodium salt osmotically active laxatives work?

A

Cause water retention in small and large bowel to increase peristalsis.

47
Q

How quickly do magnesium and sodium salt osmotically active laxatives work?

A

Quickly, severe.

48
Q

What is the route of administration of magnesium and sodium salt osmotically active laxatives?

A

PR.

49
Q

What are the indications for use of magnesium and sodium salt osmotically active laxatives?

A

Resistant constipation or if urgent relief is required (can clear bowel for surgery).

50
Q

What is the mechanism of action of lactulose (osmotically active laxative)?

A

Can’t be hydrolysed by digestive enzymes, fermentation of lactulose by colon bacteria leads to acetic and lactic acid which has an osmotic effect.

51
Q

What is the route of administration of lactulose (osmotically active laxative)?

A

Oral.

52
Q

How long does lactulose (osmotically active laxative) take to work?

A

48 hours.

53
Q

What is a contraindication for use of osmotic laxatives?

A

Intestinal obstruction.

54
Q

What is the route of administration of macrogols (osmotically active laxative)?

A

Orally with fluid (powder form).

55
Q

How long does macrogols (osmotically active laxative) take to work?

A

Initial effect within hours but 2-4 days to get full relief.

56
Q

What is the mechanism of action of irritant/stimulant laxatives?

A

Excitation of sensory nerve endings leads to water and electrolyte retention and therefore peristalsis.

57
Q

What is the indication of use of irritant/stimulant laxatives?

A

Rapid treatment for surgical prep or faecal impaction.

58
Q

How long does it take for irritant/stimulant laxatives to work?

A

6-8 hours.

59
Q

What are the risks of repeated use of irritant/stimulant laxatives?

A

Colonic atony, hypokalaemia.

60
Q

What are the groups of irritant/stimulant laxatives and which is used most?

A

Castor oil, bisacodyl, anthraquinones (most used).

61
Q

What is a risk of abuse of anthraquinone group of irritant/stimulant laxatives?

A

Melanosis coli.

62
Q

What type of laxative should be given if the patient has soft faeces?

A

Stimulant laxatives.

63
Q

Which types of laxative should be given if a patient has hard faeces?

A

Osmotic laxatives, bulk-forming laxatives.

64
Q

What are the three key types of diarrhoea?

A

Anti-motility, bulk forming, fluid adsorbents.

65
Q

What is the mechanism of action of anti-motility drugs?

A

Reduce bowel motility - increase time for fluid to reabsorb, increase anal tone and reduce sensory defecation reflex.

66
Q

What is an indication and a contraindication for anti-motility drugs?

A

Indication - chronic diarrhoea, CI - IBD (risk of toxic megacolon).

67
Q

Name two anti-motility drugs and their type.

A

Codeine (opiate analgesic), and loperamide/Imodium (opiate analogue).

68
Q

What are indications for use of bulk forming anti-diarrhoetics?

A

IBS and ileostomy.

69
Q

Name a fluid adsorbent.

A

Kaolin.

70
Q

What is cholestyramine?

A

Bile acid sequestrant.

71
Q

What is the treatment for irritable bowel syndrome?

A

Mebeverine.

72
Q

What is the action of mebeverine in IBS?

A

Affects colonic hypermotility, relieves spasm of intestinal muscle.

17. Clinical Pharmacology and Therapeutics (25 decks)

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