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Pharmacology > Drugs Affecting Gut Motility > Flashcards

Drugs Affecting Gut Motility Flashcards

1
Q

What happens when a wave of depolarisation occurs in myogenic control in the intestines?

A

Causes rhythmic contraction of smooth muscle forming

  • segmenting seen in small intestine
  • haustral shuttling in large intestine
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2
Q

Where does neural control come from?

A

Intrinsically - enteric plexus

Extrinsically

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3
Q

Effect of the sympathetic and parasympathetic nervous system on gut motility?

A

Sympathetic - reduces motility via adrenergic receptors

Parasympathetic - increases motility via cholinergic receptors and vagus nerve

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4
Q

Where does the plexus for intrinsic control lie?

A

Myenteric plexus lies between the circular and longitudinal muscle layers

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5
Q

What is the enteric nervous system? What plexuses is it made up of?

A

An autonomous collection of nerves within the gut wall

Myenteric - between circular and longitudinal muscle layers
Meissner’s - in submucosa
Henle’s
Cajal’s

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6
Q

What are the reflexes allowing extrinsic control of the gut?

A

Intestine-inhibitory reflex: distension of one intestinal segment causes complete intestinal inhibition

Anointestinal inhibitory reflex: distension of the anus causes intestinal inhibition

Gastrocolic and duodenocolic reflexes: stimulates motility after material has entered the stomach/duodenum

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7
Q

What are the hormones involved in the control of the gut and where are they secreted from?

A

Gastric: promotes acid secretion

Secretin: from the duodenum

CCK: from the small intestine

Motilin : from the small intestine

Paracrine: histamine, somatostatin, prostaglandins

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8
Q

Possible causes of constipation?

A 
Diabetes
Parkinson's
Dehydration
Pregnancy
Mechanical obstruction
Cancer
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9
Q

Which types of drugs are given for soft faeces? Examples?

A

Stimulant laxatives eg Senna, bisacodyl, glycerol

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10
Q

Which types of drugs are given for hard faeces in constipation? Examples?

A

Osmotic laxative eg Movicol

Bulk laxative eg Ispaghula

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11
Q

Non-pharmacological interventions for constipation?

A

Increase fluid intake
High fibre diet
Exercise

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12
Q

What can excessive use of laxatives lead to?

A

Hypokalaemia due to excessive enteral loss of potassium

This can then itself cause bowel inertia

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13
Q

How do bulk laxatives work?

A

Insoluble, non-absorbable substances which distend the gut

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14
Q

When can bulk laxatives be used?

A

To restore normal bowel habit in chronic or simple constipation

  • IBS
  • pregnancy
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15
Q

ADRs of bulk laxatives (eg Ispaghula)

A

Flatulence

Adhesions or ulceration that may cause intestinal obstruction

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16
Q

Name some fecal softeners

A

Arachis oil

Glycerol

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17
Q

How do faecal softeners work?

A

Lubricate and soften stools - safe but not always effective

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18
Q

Indications for faecal softeners?

A

Hard stools
Adhesions - no risk of obstruction
Anal fissures
Haemorrhoids

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19
Q

Name some osmotically active laxatives

A

Magnesium and sodium salts
Lactulose
Macrgols

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20
Q

How do magnesium and sodium salts work?

A

Cause way retention in the small and large bowel which increases peristalsis

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21
Q

How long does it take for Ispaghula to work?

A

A couple of days

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22
Q

How long does it take for magnesium and sodium salts to work?

A

Quickly and are severe

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23
Q

How are magnesium and sodium salts normally administered?

A

PR

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24
Q

When are magnsrium and sodium salts normally used?

A

Resistant constipation

If urgent relief is required

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25
Q

Mechanism of action of lactulose?

A

It is a disaccharide (galactose or fructose)
Cannot be hydrolysed by digestive enzymes
Fermented to lactulose by colon bacteria producing acetic and lactic acid
They have an osmotic effect

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26
Q

How long does it take for lactulose to work?

A

48 hours

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27
Q

Indications for lactulose?

A

Liver failure to reduce ammonia production

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28
Q

How do macrogols such as Movicol work?

A

Osmotic laxative

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29
Q

How is macrogol administered?

A

A powder dissolved in fluid

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30
Q

How long does macrogol take to work?

A

Within hours

2-4 days to get full relief

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31
Q

How do irritant/stimulant laxatives work?

A

Excite sensory nerve endings leading to water and electrolyte retention and therefore peristalsis

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32
Q

Indications for irritant/stimulant laxatives?

A

Soft faeces

  • rapid treatment eg in faecal impaction or surgical prep
  • colonic atony
  • hypokalaemia
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33
Q

How long do irritant laxatives take to have an effect and when are they given?

A

6-8 hours
Before bed
Taken orally

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34
Q

Examples of irritant/stimulant laxatives?

A 
Castor oil
Bisacodyl
Anthraquinones 
-danthron 
-Senna
-rhubarb roots
35
Q

Why can anthraquinones not be used in intestinal obstruction?

A

Cause abdominal cramps

36
Q

What is docusate sodium?

A

A faecal softener

-can be combined with danthron to give codanthraner

37
Q

What can abuse of anthraquinones lead to?

A

Melanosis coli

38
Q

Main types of anti-diarrhoeals?

A

Anti-motility
Bulk-forming - fluid absorbents
Fluid adsorbents

39
Q

Name some anti-motility drugs

A

Opiate analgesics eg codeine

Opiate analogues eg loperamide (Imodium)

40
Q

Mechanism of action of anti-motility drugs?

A

Act via opioid receptors in the bowel to

  • reduce bowel motility - increases time for fluid to reabsorption
  • increase anal tone and reduce sensory defacation reflex
41
Q

Indications for anti-motility drugs?

A

Chronic diarrhoea

42
Q

Contra-indications for anti-motility drugs?

A

IBD due to risk of toxic mega colon

43
Q

Mechanism of action of bulk-forming drugs in diarrhoea (eg Ispaghula)

A

Absorb water

44
Q

Indications for bulk-forming agents?

A

Patients with IBS - good for constipation and diarrhoea

Ileostomy

45
Q

Name a fluid adsorbent

A

Kaolin

46
Q

How does cholestyramine work?

A

It is a bike acid sequestration used for bile salt-induced diarrhoea seen in crohn’s or post-vagotomy

47
Q

What are pancreatic enzymes helpful for?

A

Diarrhoea

48
Q

Symptoms of IBS?

A 
Nausea
Vomiting
Belching 
Abdominal discomfort
Frequent bowel actions 
Constipation 
No blood loss
49
Q

What happens in IBS?

A

Chronic, re-lapsing condition where abdominal pain is associated with defacation or change in bowel habit

Abnormal smooth muscle activity or visceral hypersensitivity

50
Q

Treatment of IBS?

A

Mebeverine - anti spasmodic - anti-muscarinic

  • has direct effects on colonic hypermotility
  • relieves spasm of intestinal muscle
51
Q

What is mebeverine normally combined with?

A

A bulk-forming agent - fybogel mebeverine

52
Q

What are some other anti-spasmodics?

A

(Mebeverine)

Hyoscine

53
Q

What happens in emesis?

A

Pyloric sphincter closes while the cardia and oesophagus relax

Gastric contents propelled by contraction of abdominal wall and diaphragm

Glottis closes with elevation of the soft palate to prevent entry of vomit into the trachea or nasopharynx

54
Q

Preliminary signs of vomiting?

A 
Nausea
Dilated pupils
Increased salivation
Sweating
Retching 
Paleness
55
Q

Where is the vomiting centre?

A

In the ependymal cells (postrema) on the floor of the fourth ventricle in the brain

56
Q

What can activate the vomiting centre?

A 
Medications
Pregnancy
Toxins
Pain
Irritation 
Smell
Touch (gag)
Raised ICP
Stomach inflammation 
Rotation
57
Q

Neurotransmitters involved in vomiting?

A

Vestibular apparatus - Ach and histamine (H1)
Medullary centre - Ach, H1, 5-HT
Vomiting centre - dopamine

58
Q

What drugs are used to prevent vomiting

A

Dopamine receptor D2 antagonists - eg metoclopramide or domperidone

5-HT3 receptor antagonists eg ondansteron

Anti-muscarinics

H1 receptor antagonists eg cyclizine, promethazine

Others eg cannabinoids, benzodiazepines

59
Q

Mechanism of action of domperidone?

A

Acts on postrema on floor of fourth ventricle
Acts on stomach to increase gastric emptying

Antagonises dopamine

60
Q

Administration of domperidone?

A

Administered orally

61
Q

Indications for domperidone?

A

Acute nausea and vomiting episode

-especially if induced by L-DOPA or dopamine agonists

62
Q

ADRs of domperidone?

A

Excessive prolactin release causing galactorrhoea

Occasionally dystonia

63
Q

When is 5-HT released into the GI tract and from where?

A

Released when there are poisonous compounds, bacterial toxins, drugs etc
From enterochromaffin cells lining the GI tract

64
Q

Where does the vomiting centre receive signals from?

A

5-HT triggering vagal afferents
Vestibular apparatus which receives input from labyrinth
Medullary centre which senses emetic stimuli
Higher cortical centres - pain, sights, smells, emotional factors

Medullary centre also receives input from those three

65
Q

Mechanism of action of 5-HT antagonists

A

Effective in the postrema of the fourth ventricle, against vagal afferent nerves in the GI, medullary centre

66
Q

Indications for 5-HT antagonists?

A

Radiation therapy

Chemotherapy

67
Q

Administration of 5-HT antagonists?

A

IV
IM
Orally

68
Q

What can enhance the anti-emetic effect of 5-HT antagonists?

A

A single dose corticosteroid

69
Q

ADRs of 5-HT antagonists?

A

Headache
Constipation
Flushing (IV)

70
Q

Mechanism of action of metoclopramide?

A

D2 antagonist via fourth ventricle
Has anticholinergic effects (GI tract)
Blocks vagal afferent 5-HT (GI)

71
Q

Indications for metoclopramide?

A

GI cause of nausea and vomiting
Migraine
Post-op

72
Q

Routes of administration of metoclopramide?

A

Oral
IM
IV

73
Q

Half-life of metoclopramide?

A

4 hours

74
Q

ADRs of metoclopramide?

A

Extra-pyramidal reactions (dystonia) - so avoid in Parkinson’s

Galactorrhoea due to release of prolactin

75
Q

Mechanism of action of hyoscine? (Anti-emetic)

A

Ach antagonist

76
Q

Indications for hyoscine?

A

Prevention and treatment of motion sickness

77
Q

Administration and half life of hyoscine?

A

Oral or latch

2 hours

78
Q

ADRs of hyoscine?

A

Systemic anti-cholinergic effects such as

  • bradycardia
  • dry mouth
79
Q

Mechanism of cyclizine?

A

H1 antagonist

80
Q

Indications for cyclizine?

A

Acute nausea and vomiting

81
Q

Administration of cyclizine?

A

Oral
IV
IM

82
Q

ADRs of cyclizine?

A

Prolonged QT, reducing cardiac index in myocardial ischaemia

Sedative as can cross BBB

83
Q

What are the pacemaker cells of myogenic control of the gut?

A

Interstitial cells of cajal act as pacemakers by producing slow waves of depolarisation which travel thought the smooth muscle across gap junctions

Pharmacology (23 decks)

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