Drugs Affecting Gut Motility Flashcards
1
Q
What are the categories of control of gastric motility?
A
- Myogenic
- Neuronal
- Hormonal
2
Q
What causes the stomach to contract rhytmically?
A
Slow waves of depolarisation throughout the smooth muscle
3
Q
What allows the stomach smooth muscle to contract in a coordinated manner?
A
Passive current spread through gap junctions
4
Q
What acts as a pacemaker to drive electrical activity in the stomach?
A
Interstitial cells of Cajal
5
Q
Is neural control of gut motility intrinsic or extrinsic?
A
Elements of both
6
Q
What causes an increase in the force of contraction of the gut?
A
Stimulation of the post-ganglionic cholinergic enteric nerves
7
Q
What inhibits the contraction of the gut?
A
Stimulation of non-adrenergic inhibitory nerves
8
Q
What provides the local nerves to the stomach?
A
Enteric nervous system
9
Q
What is the enteric nervous system?
A
An autonomous collection of nerves within the gut wall
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
11
Q
Where is Auerbach’s plexus found?
A
Between circular and longitudinal muscle layers
12
Q
Where is Meissner’s plexus found?
A
In the submucosa
13
Q
Where is Henle’s plexus found?
A
In circular muscle adjacent to submucosa
14
Q
Where is Cajal’s plexus found?
A
In circular muscle adjacent to longitudinal muscle
15
Q
What gastric reflexes are provided by extrinsic nerves?
A
- Intestino-intestinal inhibitory reflex
- Anointestinal inhibitory reflex
- Gastrocolic and duodenocolic reflexes
16
Q
What is the intestino-intestinal inhibitory reflex?
A
Distention of one intestinal segment causes complete intestinal inhibition
17
Q
What happens in the anointestinal inhibitory reflex?
A
Distention of the anus causes intestinal inhibition
18
Q
What is the purpose of the gastrocolic and duodenocolic reflexes?
A
Stimulates motility after material has entered stomach or duodenum
19
Q
What kind of endocrine hormones are found in the GI tract?
A
Peptide
20
Q
Where are the endocrine hormones effective in the GI tract produced?
A
In endocrine cells of the mucosa
21
Q
What neurotransmitters are found in the GI tract?
A
- Gastrin
- Secretin
- Cholecystokinin
- Motilin
- Paracrine transmitters
22
Q
What is the function of gastin?
A
Promotion of acid secretion
23
Q
Where is secretin found?
A
In the duodenum
24
Q
Where does secretin act?
A
In the duodenum
25
Where does cholecystokinin act?
In the small intestine
26
Where does motilin act?
In the small intestine
27
What paracrine transmitters are important in the GI tract?
* Histamine
* Somatostatin
* Prostaglandins
28
What happens in emesis?
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
29
What can cause vomiting?
* Pregnany
* Medications, toxins, pain, and irradiation
* Smell or touch
* Increased intracranial pressure
* Inflammation or stretching of the stomach
* Rotational movement
30
Where is the vomiting center found?
The chemosensory trigger zone
31
What are the preliminary signs of nausea?
* Nausea
* Dilated pupils
* Increased salivation
* Outbreak of sweat
* Retching
* Paleness
32
What structures are involved in emesis control?
* Vestibular apparatus
* Medullary centre
* Postreme on the floor of the 4th ventricle
33
What receptors are found in the vestibular apparatus?
* Acetyl choline
* Histamine
34
What receptors are found in the medullary centre?
* Acetyl choline
* Histamine
* 5-hydroxytyptamine
35
What receptors are found in the postrema on the floor of the 4th ventricle?
Dopamine
36
What are the categories of anti-emesis drugs?
* Dopamine receptor antagonists
* 5HT3 receptor antagonist
* Anti-muscarinics
* Histamine receptor antagonists
* Cannabinoids
* Benzodiazapines
37
Give three examples of dopamine receptor antagonists
* Domperidone
* Metoclopramide
* Phenothiazines
38
Give two examples of 5-HT3 receptor antagonists
* Ondansteron
* Granisetron
39
Give an example of an anti-muscarinic
Hyoscine
40
Give two examples of histamine receptor antagonists
* Cyclizine
* Promethazine
41
Give an example of a cannabinoid
Nabilone
42
Give an example of a benzodiazapine?
Lorazapam
43
Where does domperidone act?
On the postrema on the floor of the 4th ventricle
44
What is the action of domperidone?
Increases rate of gastric emptying
45
Where is domperidone indicated?
In acute nausea/vomiting, especially if induced by L-dopa or dopamine agonists
46
How is domperidone administered?
Oral or PR
47
Why is domperidone not always effective when given orally?
As the patient has nausea and vomiting, so may not keep it down
48
Is domperidone affected by first pass metabolism?
Yes, extensively
49
Does domperidone cross the blood-brain barrier?
No
50
What are the adverse drug reactions of domperidone?
* Stimulates prolactin release, causing galactorrhoea
* *Rarely,* dystonia
51
What happens when 5-HT is released into the gut?
It causes vagal stimulation
52
Where does ondansteron act?
On postrema on the floor of the 4th ventricle
53
How does ondansteron act?
It acts against vagal afferent nerves in the GI to reduce release of 5-HT
54
Where is ondansteron indicated?
* In high doses in radiation sickness and chemotherapy
* Post-operative
55
How is ondansteron administered?
* IV
* IM
* Orally
56
What is the dose of ondansteron dependant on?
Indication
57
How can the anti-emetic effect of ondansteron be enhanced?
By a single dose of corticosteroids
58
What are the adverse drug reactions of ondansteron?
* Headaches
* Constipation
* Flushing
59
How does metaclopramide achieve its function?
* 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
60
What are the indications for metoclopramide?
* GI cause of nausea and vomiting
* Migraine
* Post-op
61
What are the routes of administration for metoclopramide?
* Oral
* Intramuscular
* Intravascular
62
What is the half life of metoclopramide?
4 hours
63
What are the adverse drug reactions of metoclopramide?
Extra-pyramidal reactions (such as dystonia)
64
What % of patients get extra-pyramidal reactions with metoclopramide?
1%
65
What should be done due to the risk of extra-pyramidal reactions with metoclopramide?
Should avoid in Parkinsons disease due to risk of galactorrhoea
66
What is hyoscine also known as?
Scopolamine
67
What is the mechanism of action of hyoscine?
Direct antagonist of muscarinic cholinergic receptors
68
What are the indications for hyoscine?
* Motion sickness
* Palliative care
69
How is hyoscine administered?
* Oral
* Patch
70
How often is hyoscine given orally in motion sickness?
30 minutes before motion, and then 6 hourly
71
How long do the effects of hyoscine usually act?
2 hours
72
What are the adverse drug reactions of hyoscine?
Systemic anti-cholingeric effects, *such as bradycardia*
73
What tolerance has been reported with hyoscine?
Transdermal hyoscine
74
How does cyclizine differ from other histamine antagonists?
Has additional anti-muscarinic effects
75
What are the indications for cyclizine?
Acute nausea and vomiting
76
How can cyclizine be administered?
* Oral
* IV
* IM
77
Where is cyclizine contraindicated?
Myocardial ischaemia *and similar conditions*
78
Why is cyclizine contraindicated in myocardial ischaemia?
Because it can cause QT prolongation
79
Does cyclizine cross the blood-brain barrier?
Yes
80
What is the result of cyclizine crossing the blood-brain barrier?
Sedative effect
81
What are the uses for promethazine?
* May suppress nausea following surgery, or gastric irritation/opioid induced nausea
* Useful if sedation required
82
What are the categories of laxatives?
* Non-pharmacological
* Bulk
* Faecal softners
* Osmotic
* Irritant/stimulants
83
Give an example of a bulk laxative
Fybogel
84
Give an example of a faecal softner?
Glycerol
85
Give three examples of osmotic laxatives
* Lactulose
* Macrogols
* Phosphate enemas
86
Give three examples of irritant/stimulant laxatives
* Castor oil
* Senna
* Sodium picosulfate
87
What are the non-pharmacological approaches to constipation?
* Consider underlying medical cause
* Increased fluid intake
* High fibre diet
* Exercise
88
What underlying medical causes could cause constipation?
* Diabetes
* Parkinson's disease
* Dehydration
* Pregnancy
* Mechanical obstruction
* Cancer
89
What are bulk laxatives?
Insoluble and non-absorbable substances which distend the gut
90
How do bulk laxatives work?
They draw water into the gut, which bulks up stool and stimulates peristalsis
91
Give an example of a bulk laxative
Ispaghula
92
What is ispaghula?
A vegetable fibre
93
What is the importance of ispaghula being a fibre?
It means it is resistant to digestive enzymes
94
How long do bulk laxatives take to work?
Few days
95
What do bulk laxatives attempt to do?
Re-establish normal bowel habit
96
Where are bulk laxatives indicated?
Chronic or simple constipation related to IBS, pregnancy etc
97
What is essential for the use of bulk laxatives?
Normal fluid intake
98
What are the ADRs for bulk laxatives?
Flatulence
99
What are the contraindications for bulk laxatives?
Adhesions or ulcerations
100
Why are bulk laxatives contraindicated in adhesions and ulcerations?
May cause intestinal obstruction
101
How are faecal softners administered?
By enemas, or suppositories
102
Give two examples of faecal softners?
* Arachis oil
* Glycerol
103
How do faecal softners work?
They lubricate and soften stool
104
What are the indications for faecal softners?
As per bulk laxatives, but also can be used with adhesions, and anal fissures/haemorrhoids
105
Give three examples of osmotically active laxatives
* Magnesium and sodium salts
* Lactulose
* Macrogols
106
How are magnesium and sodium salts administered?
Saline pugative enema
107
How do magnesium and sodium salts work in constipation?
They cause water retention in the small and large bowel to increase peristalsis
108
Describe the onset of action of magnesium and sodium salts
They act quickly and are severe
109
What are the indications for magneisum and sodium salts?
Usually reserve for 'resistant' constipation, and if urgent relief required
110
What is lactulose?
A disaccharide of glucose and fructose
111
How does lactulose work?
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
How is lactulose administered?
Orally
113
How long does lactulose take to work?
48 hours
114
Why is lactulose given in liver failure?
Because of the reduced production of ammonia
115
Give an example of a macrogol
Movicol (polyethylene glycol)
116
How is movicol administered?
Powder, *hence given orally with fluid*
117
How long does movicol take to work?
* Initial effects within hours
* Takes 2-4 days to get full relief
118
Why is caution required with osmotic laxatives?
To prevent intestinal obstruction
119
How do irritant/stimulant laxatives work?
They excite sensory nerve endings, leading to water and electrolyte retention, and thus peristalsis
120
What are irritant/stimulant laxatives used for?
Rapid treatment, *e.g. faecal impaction or surgical prep*
121
How long do irritant/stimulant laxatives take to act?
6-8 hours orally
122
What is the result of irritant/stimulant laxatives taking 6-8 hours to work?
Bedtime prescription
123
What can repeated use of irritant/stimulant laxatives cause?
* Colonic atony, *thus constipation*
* Hypokalaemia
124
How long does Castor oil take to work?
3 hours
125
Give three examples of anthraquinones
* Danthron
* Senna plant
* Rhubarb roots
126
What is the most frequently used irritant/stimulant laxative?
Anthraquinone group
127
What is codanthramer?
Danthron (an anthraquinone) plus a faecal softener
128
What happens to anthraquinones in the intestines?
Some derivatives are absorbed in the small intestine and excreted into the colon along with those that have escaped absorption
129
What are the adverse drug reactions for anthraquinones?
* Abdominal cramps
* Melanosis coli in abuse
130
What are the contraindications for anthraquinones?
Intestinal obstruction
131
What laxative should be given if the history and/or examination reveals soft faeces?
Stimulant laxatives, *e.g. senna, bisacodyl, glycerol*
132
What laxative should be given if history and digital rectal examination reveals hard faeces?
* Osmotic laxatives, *e.g. Movicol*
* Bulk-forming laxatives, *e.g. ispaghula*
133
What might diarrhoea represent?
Overflow in constipation
134
What is the problem with anti-diarrhoeal drugs?
They treat symptoms, not the cause
135
What is important in diarrhoea?
Appropriate fluid/electrolyte management
136
What are the three key types of anti-diarrhoea drugs?
* Anti-motility
* Bulk forming
* Fluid adsorbents
137
What can act as anti-motility drugs in diarrhoea?
* Opiate analgesics, *such as codeine*
* Opiate analogues, *such as loperamide*
138
What is the advantage of opiate analogues compared to opiate analgesics in diarrhoea?
* They are 40 times more potent than morphine as an anti-diarrhoeal agent
* Penetrates the CNS poorly
139
How do opiates and opiate analogues act in diarrhoea?
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
Where are anti-motility drugs useful?
Chronic diarrhoea
141
Where should the use of anti-motility drugs be avoided?
In IBD
142
Why should anti-motility drugs be avoided in IBD?
Due to the risk of toxic megacolon
143
How much faecal fluid influences its composition?
10-20ml - *relatively small amount*
144
Give an example of a drug that acts in diarrhoea via water absorption
Ispaghula
145
Where are bulk forming agents particularly useful in diarrhoea?
* Patients with IBS
* Those with ileostomy
146
Give an example of a drug that acts in diarrohea via fluid adsorbtion
Kaolin
147
What is the result in the increased fluid adsorbtion caused by kaolin?
Produces a more formed stool
148
What is cholestyramine?
A bile acid sequestrant
149
What is cholestyramine used for?
Bile saly induced diarrhoea (Crohns/post-vagotomy)
150
Where are pancreatic enzymes used in diarrhoea?
When diarrhoea is due to pancreatic malabsorption
151
What drug is used in the treatment of irritable bowel syndrome?
Mebeverine
152
What is mebeverine?
A reserpine derivative
153
How does mebeverine work in irritable bowel syndrome?
It has direct effects on colonic hypermotility, relieving spasms of intestinal muscle
154
Does mebeverine produce anti-muscarinic side effects?
No
155
What can mebeverine be combined with to increase its usefulness?
* Bulk forming agents
* Other smooth muscle relaxants, *e.g. peppermint oil and alverine*
