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5: Y5 - ESA 5 - Pharmacology > Drugs Affecting Gut Motility > Flashcards

Drugs Affecting Gut Motility Flashcards

1
Q

What are the categories of control of gastric motility?

A
  • Myogenic
  • Neuronal
  • Hormonal
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2
Q

What causes the stomach to contract rhytmically?

A

Slow waves of depolarisation throughout the smooth muscle

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3
Q

What allows the stomach smooth muscle to contract in a coordinated manner?

A

Passive current spread through gap junctions

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4
Q

What acts as a pacemaker to drive electrical activity in the stomach?

A

Interstitial cells of Cajal

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5
Q

Is neural control of gut motility intrinsic or extrinsic?

A

Elements of both

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6
Q

What causes an increase in the force of contraction of the gut?

A

Stimulation of the post-ganglionic cholinergic enteric nerves

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7
Q

What inhibits the contraction of the gut?

A

Stimulation of non-adrenergic inhibitory nerves

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8
Q

What provides the local nerves to the stomach?

A

Enteric nervous system

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9
Q

What is the enteric nervous system?

A

An autonomous collection of nerves within the gut wall

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10
Q

What plexuses are involved in neuronal control of gastric motility?

A
  • Auerbach’s plexus
  • Meissner’s plexus
  • Henle’s plexus
  • Cajal’s plexus
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11
Q

Where is Auerbach’s plexus found?

A

Between circular and longitudinal muscle layers

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12
Q

Where is Meissner’s plexus found?

A

In the submucosa

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13
Q

Where is Henle’s plexus found?

A

In circular muscle adjacent to submucosa

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14
Q

Where is Cajal’s plexus found?

A

In circular muscle adjacent to longitudinal muscle

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15
Q

What gastric reflexes are provided by extrinsic nerves?

A
  • Intestino-intestinal inhibitory reflex
  • Anointestinal inhibitory reflex
  • Gastrocolic and duodenocolic reflexes
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16
Q

What is the intestino-intestinal inhibitory reflex?

A

Distention of one intestinal segment causes complete intestinal inhibition

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17
Q

What happens in the anointestinal inhibitory reflex?

A

Distention of the anus causes intestinal inhibition

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18
Q

What is the purpose of the gastrocolic and duodenocolic reflexes?

A

Stimulates motility after material has entered stomach or duodenum

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19
Q

What kind of endocrine hormones are found in the GI tract?

A

Peptide

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20
Q

Where are the endocrine hormones effective in the GI tract produced?

A

In endocrine cells of the mucosa

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21
Q

What neurotransmitters are found in the GI tract?

A
  • Gastrin
  • Secretin
  • Cholecystokinin
  • Motilin
  • Paracrine transmitters
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22
Q

What is the function of gastin?

A

Promotion of acid secretion

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23
Q

Where is secretin found?

A

In the duodenum

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24
Q

Where does secretin act?

A

In the duodenum

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25
Q

Where does cholecystokinin act?

A

In the small intestine

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26
Q

Where does motilin act?

A

In the small intestine

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27
Q

What paracrine transmitters are important in the GI tract?

A
  • Histamine
  • Somatostatin
  • Prostaglandins
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28
Q

What happens in emesis?

A
  1. The pyloric sphincter closes while the cardia and oesophagus relax
  2. Gastric contents is propelled by contraction of the abdominal wall and diaphragm
  3. The glottis closes with elevation of the soft palate, preventing entry of vomit into the trachea and nasopharynx
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29
Q

What can cause vomiting?

A
  • Pregnany
  • Medications, toxins, pain, and irradiation
  • Smell or touch
  • Increased intracranial pressure
  • Inflammation or stretching of the stomach
  • Rotational movement
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30
Q

Where is the vomiting center found?

A

The chemosensory trigger zone

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31
Q

What are the preliminary signs of nausea?

A
  • Nausea
  • Dilated pupils
  • Increased salivation
  • Outbreak of sweat
  • Retching
  • Paleness
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32
Q

What structures are involved in emesis control?

A
  • Vestibular apparatus
  • Medullary centre
  • Postreme on the floor of the 4th ventricle
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33
Q

What receptors are found in the vestibular apparatus?

A
  • Acetyl choline
  • Histamine
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34
Q

What receptors are found in the medullary centre?

A
  • Acetyl choline
  • Histamine
  • 5-hydroxytyptamine
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35
Q

What receptors are found in the postrema on the floor of the 4th ventricle?

A

Dopamine

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36
Q

What are the categories of anti-emesis drugs?

A
  • Dopamine receptor antagonists
  • 5HT3 receptor antagonist
  • Anti-muscarinics
  • Histamine receptor antagonists
  • Cannabinoids
  • Benzodiazapines
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37
Q

Give three examples of dopamine receptor antagonists

A
  • Domperidone
  • Metoclopramide
  • Phenothiazines
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38
Q

Give two examples of 5-HT3 receptor antagonists

A
  • Ondansteron
  • Granisetron
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39
Q

Give an example of an anti-muscarinic

A

Hyoscine

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40
Q

Give two examples of histamine receptor antagonists

A
  • Cyclizine
  • Promethazine
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41
Q

Give an example of a cannabinoid

A

Nabilone

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42
Q

Give an example of a benzodiazapine?

A

Lorazapam

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43
Q

Where does domperidone act?

A

On the postrema on the floor of the 4th ventricle

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44
Q

What is the action of domperidone?

A

Increases rate of gastric emptying

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45
Q

Where is domperidone indicated?

A

In acute nausea/vomiting, especially if induced by L-dopa or dopamine agonists

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46
Q

How is domperidone administered?

A

Oral or PR

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47
Q

Why is domperidone not always effective when given orally?

A

As the patient has nausea and vomiting, so may not keep it down

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48
Q

Is domperidone affected by first pass metabolism?

A

Yes, extensively

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49
Q

Does domperidone cross the blood-brain barrier?

A

No

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50
Q

What are the adverse drug reactions of domperidone?

A
  • Stimulates prolactin release, causing galactorrhoea
  • Rarely, dystonia
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51
Q

What happens when 5-HT is released into the gut?

A

It causes vagal stimulation

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52
Q

Where does ondansteron act?

A

On postrema on the floor of the 4th ventricle

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53
Q

How does ondansteron act?

A

It acts against vagal afferent nerves in the GI to reduce release of 5-HT

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54
Q

Where is ondansteron indicated?

A
  • In high doses in radiation sickness and chemotherapy
  • Post-operative
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55
Q

How is ondansteron administered?

A
  • IV
  • IM
  • Orally
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56
Q

What is the dose of ondansteron dependant on?

A

Indication

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57
Q

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

A

By a single dose of corticosteroids

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58
Q

What are the adverse drug reactions of ondansteron?

A
  • Headaches
  • Constipation
  • Flushing
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59
Q

How does metaclopramide achieve its function?

A
  • Anti-cholinergic effects on the GI tract
  • Blocks vagal afferent 5-HT3 receptors in the GI tract
  • Dopamine antagonism acting on the 4th ventricle, causing gastric emptying
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60
Q

What are the indications for metoclopramide?

A
  • GI cause of nausea and vomiting
  • Migraine
  • Post-op
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61
Q

What are the routes of administration for metoclopramide?

A
  • Oral
  • Intramuscular
  • Intravascular
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62
Q

What is the half life of metoclopramide?

A

4 hours

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63
Q

What are the adverse drug reactions of metoclopramide?

A

Extra-pyramidal reactions (such as dystonia)

64
Q

What % of patients get extra-pyramidal reactions with metoclopramide?

A

1%

65
Q

What should be done due to the risk of extra-pyramidal reactions with metoclopramide?

A

Should avoid in Parkinsons disease due to risk of galactorrhoea

66
Q

What is hyoscine also known as?

A

Scopolamine

67
Q

What is the mechanism of action of hyoscine?

A

Direct antagonist of muscarinic cholinergic receptors

68
Q

What are the indications for hyoscine?

A
  • Motion sickness
  • Palliative care
69
Q

How is hyoscine administered?

A
  • Oral
  • Patch
70
Q

How often is hyoscine given orally in motion sickness?

A

30 minutes before motion, and then 6 hourly

71
Q

How long do the effects of hyoscine usually act?

A

2 hours

72
Q

What are the adverse drug reactions of hyoscine?

A

Systemic anti-cholingeric effects, such as bradycardia

73
Q

What tolerance has been reported with hyoscine?

A

Transdermal hyoscine

74
Q

How does cyclizine differ from other histamine antagonists?

A

Has additional anti-muscarinic effects

75
Q

What are the indications for cyclizine?

A

Acute nausea and vomiting

76
Q

How can cyclizine be administered?

A
  • Oral
  • IV
  • IM
77
Q

Where is cyclizine contraindicated?

A

Myocardial ischaemia and similar conditions

78
Q

Why is cyclizine contraindicated in myocardial ischaemia?

A

Because it can cause QT prolongation

79
Q

Does cyclizine cross the blood-brain barrier?

A

Yes

80
Q

What is the result of cyclizine crossing the blood-brain barrier?

A

Sedative effect

81
Q

What are the uses for promethazine?

A
  • May suppress nausea following surgery, or gastric irritation/opioid induced nausea
  • Useful if sedation required
82
Q

What are the categories of laxatives?

A
  • Non-pharmacological
  • Bulk
  • Faecal softners
  • Osmotic
  • Irritant/stimulants
83
Q

Give an example of a bulk laxative

A

Fybogel

84
Q

Give an example of a faecal softner?

A

Glycerol

85
Q

Give three examples of osmotic laxatives

A
  • Lactulose
  • Macrogols
  • Phosphate enemas
86
Q

Give three examples of irritant/stimulant laxatives

A
  • Castor oil
  • Senna
  • Sodium picosulfate
87
Q

What are the non-pharmacological approaches to constipation?

A
  • Consider underlying medical cause
  • Increased fluid intake
  • High fibre diet
  • Exercise
88
Q

What underlying medical causes could cause constipation?

A
  • Diabetes
  • Parkinson’s disease
  • Dehydration
  • Pregnancy
  • Mechanical obstruction
  • Cancer
89
Q

What are bulk laxatives?

A

Insoluble and non-absorbable substances which distend the gut

90
Q

How do bulk laxatives work?

A

They draw water into the gut, which bulks up stool and stimulates peristalsis

91
Q

Give an example of a bulk laxative

A

Ispaghula

92
Q

What is ispaghula?

A

A vegetable fibre

93
Q

What is the importance of ispaghula being a fibre?

A

It means it is resistant to digestive enzymes

94
Q

How long do bulk laxatives take to work?

A

Few days

95
Q

What do bulk laxatives attempt to do?

A

Re-establish normal bowel habit

96
Q

Where are bulk laxatives indicated?

A

Chronic or simple constipation related to IBS, pregnancy etc

97
Q

What is essential for the use of bulk laxatives?

A

Normal fluid intake

98
Q

What are the ADRs for bulk laxatives?

A

Flatulence

99
Q

What are the contraindications for bulk laxatives?

A

Adhesions or ulcerations

100
Q

Why are bulk laxatives contraindicated in adhesions and ulcerations?

A

May cause intestinal obstruction

101
Q

How are faecal softners administered?

A

By enemas, or suppositories

102
Q

Give two examples of faecal softners?

A
  • Arachis oil
  • Glycerol
103
Q

How do faecal softners work?

A

They lubricate and soften stool

104
Q

What are the indications for faecal softners?

A

As per bulk laxatives, but also can be used with adhesions, and anal fissures/haemorrhoids

105
Q

Give three examples of osmotically active laxatives

A
  • Magnesium and sodium salts
  • Lactulose
  • Macrogols
106
Q

How are magnesium and sodium salts administered?

A

Saline pugative enema

107
Q

How do magnesium and sodium salts work in constipation?

A

They cause water retention in the small and large bowel to increase peristalsis

108
Q

Describe the onset of action of magnesium and sodium salts

A

They act quickly and are severe

109
Q

What are the indications for magneisum and sodium salts?

A

Usually reserve for ‘resistant’ constipation, and if urgent relief required

110
Q

What is lactulose?

A

A disaccharide of glucose and fructose

111
Q

How does lactulose work?

A

It cannot be hydrolysed by digestive enzymes, so just passes through the bowel. Fermentation of lactulose by colon bacteria leads to acetic and lactic acid, which produces an osmotic effect

112
Q

How is lactulose administered?

A

Orally

113
Q

How long does lactulose take to work?

A

48 hours

114
Q

Why is lactulose given in liver failure?

A

Because of the reduced production of ammonia

115
Q

Give an example of a macrogol

A

Movicol (polyethylene glycol)

116
Q

How is movicol administered?

A

Powder, hence given orally with fluid

117
Q

How long does movicol take to work?

A
  • Initial effects within hours
  • Takes 2-4 days to get full relief
118
Q

Why is caution required with osmotic laxatives?

A

To prevent intestinal obstruction

119
Q

How do irritant/stimulant laxatives work?

A

They excite sensory nerve endings, leading to water and electrolyte retention, and thus peristalsis

120
Q

What are irritant/stimulant laxatives used for?

A

Rapid treatment, e.g. faecal impaction or surgical prep

121
Q

How long do irritant/stimulant laxatives take to act?

A

6-8 hours orally

122
Q

What is the result of irritant/stimulant laxatives taking 6-8 hours to work?

A

Bedtime prescription

123
Q

What can repeated use of irritant/stimulant laxatives cause?

A
  • Colonic atony, thus constipation
  • Hypokalaemia
124
Q

How long does Castor oil take to work?

A

3 hours

125
Q

Give three examples of anthraquinones

A
  • Danthron
  • Senna plant
  • Rhubarb roots
126
Q

What is the most frequently used irritant/stimulant laxative?

A

Anthraquinone group

127
Q

What is codanthramer?

A

Danthron (an anthraquinone) plus a faecal softener

128
Q

What happens to anthraquinones in the intestines?

A

Some derivatives are absorbed in the small intestine and excreted into the colon along with those that have escaped absorption

129
Q

What are the adverse drug reactions for anthraquinones?

A
  • Abdominal cramps
  • Melanosis coli in abuse
130
Q

What are the contraindications for anthraquinones?

A

Intestinal obstruction

131
Q

What laxative should be given if the history and/or examination reveals soft faeces?

A

Stimulant laxatives, e.g. senna, bisacodyl, glycerol

132
Q

What laxative should be given if history and digital rectal examination reveals hard faeces?

A
  • Osmotic laxatives, e.g. Movicol
  • Bulk-forming laxatives, e.g. ispaghula
133
Q

What might diarrhoea represent?

A

Overflow in constipation

134
Q

What is the problem with anti-diarrhoeal drugs?

A

They treat symptoms, not the cause

135
Q

What is important in diarrhoea?

A

Appropriate fluid/electrolyte management

136
Q

What are the three key types of anti-diarrhoea drugs?

A
  • Anti-motility
  • Bulk forming
  • Fluid adsorbents
137
Q

What can act as anti-motility drugs in diarrhoea?

A
  • Opiate analgesics, such as codeine
  • Opiate analogues, such as loperamide
138
Q

What is the advantage of opiate analogues compared to opiate analgesics in diarrhoea?

A
  • They are 40 times more potent than morphine as an anti-diarrhoeal agent
  • Penetrates the CNS poorly
139
Q

How do opiates and opiate analogues act in diarrhoea?

A

They act via opioid receptors in the bowel to reduce bowel motility, which increases time for fluid to reabsorb, and by increasing anal tone and reduce sensory defecation reflex

140
Q

Where are anti-motility drugs useful?

A

Chronic diarrhoea

141
Q

Where should the use of anti-motility drugs be avoided?

A

In IBD

142
Q

Why should anti-motility drugs be avoided in IBD?

A

Due to the risk of toxic megacolon

143
Q

How much faecal fluid influences its composition?

A

10-20ml - relatively small amount

144
Q

Give an example of a drug that acts in diarrhoea via water absorption

A

Ispaghula

145
Q

Where are bulk forming agents particularly useful in diarrhoea?

A
  • Patients with IBS
  • Those with ileostomy
146
Q

Give an example of a drug that acts in diarrohea via fluid adsorbtion

A

Kaolin

147
Q

What is the result in the increased fluid adsorbtion caused by kaolin?

A

Produces a more formed stool

148
Q

What is cholestyramine?

A

A bile acid sequestrant

149
Q

What is cholestyramine used for?

A

Bile saly induced diarrhoea (Crohns/post-vagotomy)

150
Q

Where are pancreatic enzymes used in diarrhoea?

A

When diarrhoea is due to pancreatic malabsorption

151
Q

What drug is used in the treatment of irritable bowel syndrome?

A

Mebeverine

152
Q

What is mebeverine?

A

A reserpine derivative

153
Q

How does mebeverine work in irritable bowel syndrome?

A

It has direct effects on colonic hypermotility, relieving spasms of intestinal muscle

154
Q

Does mebeverine produce anti-muscarinic side effects?

A

No

155
Q

What can mebeverine be combined with to increase its usefulness?

A
  • Bulk forming agents
  • Other smooth muscle relaxants, e.g. peppermint oil and alverine

5: Y5 - ESA 5 - Pharmacology (28 decks)

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