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Clinical Pharmacology and Therapeutics > Drugs Affecting Gut Motility > Flashcards

Drugs Affecting Gut Motility Flashcards

1
Q

Breifly describe the myogenic control of the gut.

A

Rhythmic contraction co-ordinated by slow waves of depolarisation throughout the smooth muscle. Current spreads passively across gap junctions.

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2
Q

Which cells act as the gut motility pacemakers?

A

Interstitial cells of cajal

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3
Q

Which nerves stimulation increases force of gut contractions?

A

Post-ganglionic cholinergic enteric part of the ANS.

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4
Q

Which nerves inhibit guy contraction?

A

Non-adrenergic inhibitory NS

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5
Q

What is Auerbach’s plexus?

A

Nerve plexus that lies between the circular and longitudinal muscle layers

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6
Q

What is Meissner’s plexus?

A

Nerve plexus that lies within the submucosa

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7
Q

What is Hente’s plexus?

A

Nerve plexus that lies in the circular muscle adjacent to submucosa

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8
Q

What is Cajal’s plexus?

A

Nerve plexus in circular muscle adjacent to longitudinal muscle.

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9
Q

What is the main action of the intestino-interstinal inhibitory reflex?

A

Distension of one part of the intestine causes inhibition of the whole.

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10
Q

What does gastrin promote?

A

Acid secretion

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11
Q

What does cholecytokinin promote?

A

Small intestine - release of bile from gall bladder and enzymes from pancreas

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12
Q

What can we do for nausea and vomiting?

A

Give an anti-emetic

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13
Q

What is emesis?

A

Vomiting!

Gastric contents is propelled through a relaxed oesophagus and cardia due to abdominal wall and diaphragm contraction.

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14
Q

What causes emesis?

A 
Pregnancy
Medications
Toxins
Pain
Irradiation
Smell/touch
RICP
Stomach stretching or inflammation
Rotational movement
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15
Q

What central pathway is important in emesis?

A

Central chemosensory trigger zone (vomiting centre within it).

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16
Q

Which apparatus is involved in emesis?

A

Vestibular apparatus
Medullary centre
4th ventricle

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17
Q

Decribe the inputs to the medulla in the mechanism of emesis.

A

Ach and H1 from vestibular apparatus, and Dopamine from the 4th ventricle -> Medullary centre (ACh, H1, 5HT3)

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18
Q

What broad classes of drug can we use as anti-emetics?

A
  • D2 receptor antagonists
  • 5-HT3 receptor antagonists
  • Antimuscarinics
  • H1 receptor antagonists
  • Other agents
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19
Q

What other agents can be used in anti-emesis?

A

Cannabinoids e.g. nabilone

Benzodiazapines e.g. lorazepam

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20
Q

What D2 antagonists can we use as anti-emetics?

A

Domperidone
Metoclopramide
Phenothiazines

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21
Q

What 5-HT3 antagonists can we use as anti-emetics?

A

Ondansetron

Granisetran

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22
Q

What antimuscarinics can we use as anti-emetics?

A

Hyosine

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23
Q

What H1 antagonists can we use as anti-emetics?

A

Cyclizine

Promethazine

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24
Q

Which antiemetic is indicated for acute N/V?

A

Domperidone

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25
Q

Which antiemetic is indicated firts line for radiation sickness, chemotherapy sickness, or post-operatively?

A

Ondansetron

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26
Q

Which antiemetic is indicated for GI N&V, migraine sickness, or post-op most commonly?

A

Metoclompromide - most commonly prescribed anti-emetic

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27
Q

Which agent is effective for motion sickness as well as an add on in chemotherapy?

A

Hyosine

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28
Q

Which anti-emetic is the second most commonly prescribed? Why?

A

Cyclizine - different mechanism to metoclompromide but v efficacious

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29
Q

Which agent is good for opioid induced N&V?

A

Promethazine

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30
Q

Where does domperidone work?

A

Postrema on the floor of the 4th ventricle and locally in the stomach to increase the rate of gastric emptying

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31
Q

How can domperidone be given?

A

PO or PR

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32
Q

Why is PO administration not ideal in this class of drug?

A

Coz if they’re actively vomiting, how are we going to get it down them??

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33
Q

Does domperidone cross the BBB?

A

No

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34
Q

What are the potential ADRs of domperidone?

A

Galactorrhoea (stimulates prolactin release)

Dystonia (rare)

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35
Q

Where does ondansetron work?

A

Postrema on floor of 4th ventricle

Vagal afferent nerves of GI tract

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36
Q

How can ondansetron be given?

A

IV
IM
Orally

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37
Q

What can we give alongside ondansetron to increase its efficacy as an anti-emetic?

A

Single dose of a corticosteroid (prednisolone or hydocortisone).

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38
Q

What are the ADRs of ondansetron?

A

Headaches
Constipation
Flushing if given IV

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39
Q

Aside from its main effect, what other MoA does metoclopramide have?

A

Anti-cholinergic effect and blocks vagal afferent 5-HT3 receptors

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40
Q

How is metoclopramide given?

A

PO
IV
IM

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41
Q

How frequently should metoclompramide be given and why?

A

3 times a day as the t1/2 is roughly 4 hours

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42
Q

What are the ADRs associated with metoclopramide?

A

Extrapyramidal S/Es in 1% of pts

Galactorrhoea

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43
Q

Who should we avoid giving metoclopramide?

A

Parkinson’s pts

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44
Q

How can we administer hyoscine?

A

PO

Patch (transdermal)

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45
Q

How long do the effects of hyoscine usually work?

A

For roughly 2 hours

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46
Q

What ADRs are associated with hyoscine?

A

Systemic anticholinergic effect

Bradycardia

47
Q

Aside from its H1 antagonism, what other effect can cyclizine have?

A

Anti-muscarinic effects

48
Q

How can cyclizine be given?

A

PO
IV
IM

49
Q

Who should avoid cyclizine?

A

Pts with myocardial ischaemia or on medications that prolong QT interval.

50
Q

How does cyclizine have a sedative effect?

A

It crosses the BBB

51
Q

What is the major ADR associated with cyclizine?

A

QT prolongation

52
Q

What kinds of laxative are there?

A 
Non-pharmacologically
Bulk forming
Faecal softeners
Osmotic laxatives
Irritant/stimulant
53
Q

How can we target constipation non-pharmacologically?

A

By looking at the causes and treat this to treat the symptom (constipation)

54
Q

What can cause constipation?

A 
DM
PD
Dehydration
Pregnancy
Mechanical obstruction
Cancer
Drugs
55
Q

Which drugs are the worst offenders for causing constipation?

A

Opioids

56
Q

What interventions can we use to treat constipation conservatively?

A

Increase fluid intake
High fibre diet
Exercise
Stop/reduce opioids

57
Q

Other than opiods, what other drugs can cause constipation?

A 
Anticholinergics
Alluminium antacids
TCAs
SSRIs
Antiepileptics
Antipsychotics
Antispasmodics
Ca2+ supplements
Diuretics via dehydration
Iron supplements
Verapamil
58
Q

Decribe how bulk laxative work.

A

Insoluble and non-absorbable substances that cause gut distension and draw in water to stimulate peristalsis

59
Q

What diet component is most like bulk laxatives?

A

Fibre from plants/cellulose, bran, linseed, etc

60
Q

What are the 2 main bulk laxatives?

A

Fybogel

Ispaghula

61
Q

How long do bulk laxatives take to work?

A

A few days

62
Q

What is important when taking bulk laxatives?

A

Fluid intake must remian normal

Ideally pt should be on a high fibre diet.

63
Q

What is the main ADR associated with bulk laxatives?

A

Flatulance

64
Q

When are bulk laxatives contraindicated?

A

GI adhesions or ulceration

65
Q

Why are bulk laxatives contraindicated in these situations?

A

They may cause intestinal obstruction

66
Q

Enema vs suppository

A

Enema is liquid (or even sometimes gas), suppository is solid like a tablet. Both inserted into the rectum.

67
Q

What are the 2 types of faecal softeners?

A 
Arachis oil (enema)
Glycerol (suppository)
68
Q

Are faecal softeners good?

A

Safe, but not always effective

69
Q

When are faecal softeners indicated?

A

Same as bulk laxative but can also be given in the presence of adhesions, anal fissure, or haemorrhoids.

70
Q

What are the osmotically active laxatives?

A

Mg and Na salts
Lactulose
Macrogols

71
Q

What are Mg and Na salt laxative also known as?

A

Saline purgatives, or phosphate enemas

72
Q

How do saline purgatives work?

A

Cause water retention in bowel to increase peristalsis

73
Q

How quickly do salt purgatives work?

A

Very, and very effectively too.

74
Q

What is lactulose?

A

Disaccharide of galactose and fructose that cannot be hydrolysed in digestive enzymes

75
Q

How does lactulose work as a laxative?

A

Lactulose is fermented by gut bacteria to form acetic and lactic acids. These draw in water for an osmotic effect.

76
Q

How long does lactulose take to work?

A

~48 hours

77
Q

Which laxative is good in liver failure and why?

A

Lactulose as it reduced production of ammonia by gut bacteria

78
Q

What is the macrogol ive heard of?

A

Movicol i.e. polyethylene glycol

79
Q

How is movicol given?

A

Orally as a powder with fluid

80
Q

How quickly does movicol work?

A

Initially within a few hours, but full effect takes 2-4 days

81
Q

Which laxative is given most commonly 1st line in hospitals?

A

Lactulose

82
Q

What do we need to be aware of with osmotically active laxatives?

A

Caution is required to prevent intestinal obstruction

83
Q

What are the irritant/stimulant laxatives?

A

Senna
Bisacodyl
Castor oil
Sodium picosulphate

84
Q

How do irritant laxatives work?

A

Excite sensory nerve endings -> water and electoryle retention, and peristalsis

85
Q

When are irritant/stimulant laxatives used most commonly?

A

Alongside an osmotic laxative
In faecal impaction
Surgical prep

86
Q

How quickly do irritant laxatives work?

A

within 6-8 hours, so take them at night for a poop in the morning.

87
Q

What is a problem associated with repeated use of irritant laxatives?

A

Colonic atony -> constipation

Also hypokalaemia

88
Q

Tell me about castor oil.

A

Powerful laxative
Give PO
Works in ~ 3 hours for watery stool.

Obsolete clinically***

89
Q

Which of the irritant laxative are most commonly used?

A

Anthraquinones (including Senna)

90
Q

What can senna cause?

A

Abdominal cramps

91
Q

What can overuse of senna etc cause?

A

Melanosis coli

92
Q

How does senna work?

A

Broken down by gut bacteria to produce anthranol and 1,8 - dihydroxy-anthrone

93
Q

How do we decide which laxative to use?

A

By whether the stool is hard or soft, and any contraindications.

94
Q

How does long term laxative use lead to hypokalaemia?

A

Decreased water and Na uptake from gut, so increased renal retention of water and Na, in exchange for K excretion.

95
Q

What is most diarrhoea like in terms of duration?

A

Self limiting

96
Q

What do we need to keep an eye on with diarrhoea?

A

Dehydration, and electrolyte balance

97
Q

What could diarrhoea be a symptom of, if not infective in nature?

A

Constipation (overflow diarrhoea)

98
Q

What are the 3 type of anti-diarrhoea medication?

A

Antimotility
Bulk forming
Fluid absorbants

99
Q

What are the anti-motility diarrhoea drugs?

A

Opiate analgesics, or opiate alanogues

100
Q

Which opiate analgesic can we use in diarrhoea?

A

Codeine

101
Q

Why are opiate analogues better?

A

Work on opiate receptors in gut much more effectively than morphine, but don’t pass into CNS well.

102
Q

What are anti-motility diarhhoea drugs good for, and bad for?

A

Good for chronic diarrhoea

Bad for IBD (as can cause toxic megacolon)

103
Q

What opiate analogues are there?

A

Loperamide

Imodium

104
Q

Which anti-diarrhoea drugs are good for IBS or those with an ileostomy?

A

Bulk forming ones

105
Q

Why are bulk formers good for IBS pts?

A

Can be used to treat constipation and diarrhoea! Magic…..

106
Q

What is kaolin?

A

A fluid adsorbent

107
Q

Is kaolin used much?

A

No

108
Q

Are there specific drugs for specific causes of diarrhoea?

A

Yes

109
Q

What are the specific causes of diarrhoea that we can target?

A

Bilt salt induced

Pancreatic malabsorption

110
Q

How can we treat bile salt induced diarrhoea?

A

With cholestryamine, a bile acid sequestrant.

111
Q

How can we treat pancreatic insufficency-induced diarrhoea?

A

Pancreatci enzymes

112
Q

How can we treat gut hypermotility?

A

With smooth muscle relaxants such as peppermint oil, alverine, and mebeverine.

113
Q

Tell me about mebeverine.

A

Reserpine derivative.
Relieves spasms of intestinal muscle
Useful alongside a bulk forming agent
No systemic antimuscarinic ADRs

Clinical Pharmacology and Therapeutics (26 decks)

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