Nausea, vomiting and diarrhoea Flashcards

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1
Q

What actually happens in vomiting?

A
  • Co-ordinated by the vomiting centre in the medulla
  • Take a deep breath
  • Glottis closes
  • Abdominal muscles contract
  • Lower oesophageal sphincter relaxes
  • Retrograde peristalsis of small bowels
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2
Q

What are the inputs to the vomiting centre?

A
  • Higher cortical centres - pain, repulsive sights and smells, emotional factors
  • CTZ - main site for sensing emetic stimuli (receives input from the vestibular nuclei)
  • Vagal afferents convey signals from gut to brainstem
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3
Q

What do we target to treat motion sickness?

A
  • Muscarinic ACh receptors
  • H1
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4
Q

Give some examples of muscarinic antagonist drugs?

A
  • Hyoscine hydrobromide
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5
Q

What is the mechanism of action of muscarinic antagonists?

A
  • Competitive blockade of muscarinic acetylcholine receptors
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6
Q

What are the adverse side effects of anti-muscarinics?

A
  • Sedation
  • Constipation
  • Dizziness
  • Dry mouth
  • Visual problems
  • Confusion
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7
Q

What are the contraindications of anti-muscarinic drugs?

A
  • Elderly patients
  • Glaucoma
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8
Q

What are the DDIs of anti-muscarinic drugs?

A
  • Anti-psychotic medication
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9
Q

Give some examples of H1 antagonists?

A
  • Cyclizine
  • Levomepromazine
  • Prochlorperazine
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10
Q

How do H1 antagonists work?

A
  • Works centrally
  • Acts on the vomiting centre and vestibular nuclei
  • Inhibits histaminergic signals from the vestibular system to the CTZ in the medulla
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11
Q

What are the adverse side effects of H1 antagonists?

A
  • Sedation
  • Anti-muscarinic side effects e.g. dry mouth, constipation, urinary retention, blurred vision
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12
Q

What are the contraindications of H1 antagonists?

A
  • Epilepsy
  • Glaucoma
  • Urinary retention
  • Children
  • Elderly patients
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13
Q

Which H1 antagonists are sedating?

A
  • Diphenhydramine (Benadryl)
  • Promethazine
  • Chlorphenamine
  • Cinnarizine
  • Cyclizine
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14
Q

Which H1 antagonists are non sedating?

A
  • Cetirizine
  • Fexofenadine
  • Loratidine
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15
Q

Outline the epidemiology of motion sickness?

A
  • Very common
  • Affects women more than men
  • Affects children more than adults
  • People who have migraine
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16
Q

What are the practical methods of motion sickness prevention?

A
  • Hydration
  • Position in the vehicle
  • Distraction
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17
Q

What are the drugs used to treat motion sickness?

A
  • Anti-muscarinics - hyoscine (scopolamine)
  • Anti-histamines - cinnarizine, cyclizine, prochlorperazine
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18
Q

Which drugs can make a patient feel nauseous?

A
  • Chemotherapy
  • Opioids
  • General anaesthetics
  • Digoxin
  • NSAIDs
  • Diuretics
  • Antibiotics
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19
Q

Which metabolites can cause nausea?

A
  • Uraemia
  • DKA
  • Addison’s disease
  • Hyperthyroidism
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20
Q

Which toxins can cause nausea?

A
  • Bacteria
  • Viral
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21
Q

Give some examples of D2 receptor antagonists

A
  • Metoclopramide
  • Domperidone
  • Haloperidol
  • Prochlorperazine
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22
Q

Outline the mechanism of action of metoclopramide

A
  • Central dopamine antagonist
  • Peripheral cholinergic agonist
  • Increases acetylcholine at muscarinic receptors in the gut
  • Promotes gastric emptying
  • Increases tone at lower oesophageal sphincter
  • Increases tone and amplitude of gastric contractions
  • Decreases tone of pylorus so it opens
  • Increases peristalsis
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23
Q

What are the adverse side effects of metoclopramide?

A
  • Depression
  • Diarrhoea
  • Drowsiness
  • Hypotension
  • Galactorrhoea
  • Extra-pyramidal effects e.g. dystonia, parkinsonism
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24
Q

What are the contraindications of metoclopramide?

A
  • Post-GI surgery
  • GI obstruction
  • GI perforation
  • GI haemorrhage
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25
Q

How does domperidone work?

A
  • Similar mechanism to metoclopramide
  • Good for improving lactation in breastfeeding mothers
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26
Q

Why is domperidone not used as frequently anymore?

A
  • Increased risk of cardiac side effects
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27
Q

What are the adverse side effects of domperidone?

A
  • Dry mouth
  • Long QT interval
  • Ventricular tachycardia
  • Galactorrhoea
  • Loss of libido
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28
Q

What are the contraindications of domperidone?

A
  • Patients >60 years old
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29
Q

What is the mechanism of action of haloperidol?

A
  • Act on the CTZ
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30
Q

What are the adverse side effects of haloperidol?

A
  • Parkinsonism
  • Movement disorder
  • Long QT
  • Arrhythmia
  • Constipation
  • Dry mouth
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31
Q

What are the contraindications of haloperidol?

A
  • Parkinson’s disease
  • Cardiovascular disease
  • Diabetes
  • Myasthenia gravis
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32
Q

What is the mechanism of action of the ‘zines’?

A
  • Act on the CTZ
  • May also block H1 and muscarinic receptors
33
Q

What are the adverse side effects of the ‘zines’?

A
  • Drowsiness
  • Dry mouth
  • Movement disorder
  • Parkinsonism
  • Long QT
  • Urinary retention
34
Q

What are the contraindications of the ‘zines’?

A
  • Elderly patient
  • Parkinson’s disease
  • Cardiovascular disease
  • Diabetes
  • Myasthenia gravis
35
Q

What are some examples of NK-1 receptor antagonists?

A
  • Aprepitant
  • Fosaprepitant
  • Netupitant
36
Q

What is the mechanism of action of NK-1 receptor antagonists?

A
  • Prevent the action of substance P at CTZ and in peripheral nerves
  • Boosts effects of 5HT3 receptor antagonists
  • Anxiolytic and antidepressant properties
  • Good for chemotherapy - particularly for delayed emesis
37
Q

What are the adverse side effects of NK-1 receptor antagonists?

A
  • Constipation
  • Headache
  • Asthenia
38
Q

What are the contraindications of NK-1 receptor antagonists?

A
  • Acute porphyrias
39
Q

What is the mechanism of action of corticosteroids?

A
  • Assumed to act on the CTZ
  • May also have properties of D2 receptor antagonists
40
Q

What are corticosteroids good for treating?

A
  • Perioperative nausea and vomiting
  • Chemotherapy
  • Palliation
41
Q

What are the adverse side effects of corticosteroids?

A
  • Insomnia
  • Osteoporosis
  • Increased weight
  • Increased appetite
  • Increased blood sugar
  • Cushing’s syndrome
42
Q

What are the contraindications of corticosteroids?

A
  • Osteoporosis
  • Diabetes mellitus
  • Peptic ulcer
43
Q

What are some examples of corticosteroids?

A
  • Dexamethasone
  • Methylprednisolone
44
Q

What is the mechanism of action of cannabinoids?

A
  • Assumed to act on the CTZ
  • Good for chemotherapy - used as last line
45
Q

What are the adverse side effects of cannabinoids?

A
  • Confusion
  • Depression
  • Drowsiness
  • Dizziness
  • Movement disorders
  • Psychosis
  • Tremor
  • Visual impairment
46
Q

What are the contraindications of cannabinoids?

A
  • Elderly patients
  • Heart disease
  • History of psychiatric disorder
47
Q

Give an example of a cannabinoid?

A
  • Nabilone
48
Q

What can cause post-operative vomiting?

A
  • Operation itself
  • General anaesthesia/post-operative medications
  • Predisposing factors
  • Metabolic causes - uraemia, diabetic ketoacidosis, hypercalcaemia
  • Ileus
  • Bowel obstruction
49
Q

Which drugs are used to treat post-operative vomiting?

A
  • Metoclopramide
  • Prokinetics
  • Hyoscine (reduces secretions)
50
Q

Which drugs are used to treat pregnancy-induced vomiting?

A
  • Fluid replacement
  • Anti-histamines - promethazine/cyclizine
  • Phenothiazine or prochlorperazine
  • Ondansetron
  • Steroids
  • Metoclopramide and domperidone
  • Thiamine replacement
51
Q

Which drugs are used to treat chemotherapy-induced nausea and vomiting?

A
  • 5-HT3 antagonists e.g. ondansetron cover the acute emetic stimulus of chemotherapy administration only
  • Aprepitant can have a positive effect on delayed nausea and vomiting
  • Dopamine antagonists e.g. metoclopramide are more effective for delayed nausea +/- dexamethosone
  • Lorazepam or other anxiolytic treatment can help anticipatory nausea or vomiting
52
Q

Give an example of a 5-HT3 antagonist

A
  • Ondansetron
  • Granisetron
  • Palonosetron
53
Q

What is the mechanism of action of ondansetron?

A
  • Reduces GI motility and secretions
  • Acts to inhibit CTZ
  • Prevents excit
54
Q

What are the adverse side effects of 5-HT3 antagonists?

A
  • Constipation
  • Headache
  • Elevated liver enzymes
  • Long QT syndrome
  • Extra-pyramidal effects
  • Dystonia
  • Parkinsonism
55
Q

What are the contraindications of 5-HT3 antagonists?

A
  • Subacute abdominal obstruction
  • Susceptible to long QT
56
Q

What are the non-pharmacological options for treating bowel obstruction?

A
  • NG tube
57
Q

Which drugs are used to treat bowel obstruction?

A
  • Cyclizine used 1st line
58
Q

How do we treat constipation without medicine?

A
  • Healthy diet - dietary fibre intake
  • Fluid intake
  • Exercise
  • Toilet routine and positioning
59
Q

What are some examples of bulk-forming laxatives?

A
  • Ispaghula husk
  • Methylcellulose
60
Q

What is the mechanism of action of bulk-forming laxatives?

A
  • Polysaccharide polymers that are not digested in the upper part of the GI tract
  • Forms a bulky hydrated mass in the gut lumen promoting peristalsis and improving faecal consistency
61
Q

Give some examples of faecal softeners

A
  • Docusate sodium
  • Arachis oil enema
  • Liquid paraffin
62
Q

What is the mechanism of action of faecal softeners?

A
  • Acts in the GI tract in a manner similar to a detergent and produces softer faeces
  • It is also a weak stimulant laxative
63
Q

Give some examples of osmotic laxatives?

A
  • Lactulose
  • Macrogol
64
Q

What is the mechanism of action of osmotic laxatives?

A
  • Poorly absorbed in the gut
  • Lactulose: semisynthetic disaccharide of fructose and galactose
  • Macrogol: inert ethylene glycol polymers
65
Q

What are the adverse side effects of osmotic laxatives?

A
  • Flatulence
  • Cramps
  • Diarrhoea
  • Electrolyte disturbance
66
Q

Give some examples of stimulant laxatives

A
  • Bisacodyl
  • Sodium picosulfate
  • Senna
  • Glycerol suppositories
67
Q

What are the side effects of stimulant laxatives?

A
  • Abdominal cramps
  • Nausea
  • Rash
68
Q

What are the contraindications of stimulant laxatives?

A
  • Diarrhoea
  • Bowel obstruction
69
Q

What causes diarrhoea?

A
  • Drugs
  • Infection
  • Toxins/drugs
  • Radiotherapy
  • Anxiety
70
Q

Which drugs cause diarrhoea?

A
  • Domperidone (increases GI motility - mechanism unknown)
  • Metoclopramide (increases gastric emptying and motility)
  • Naloxegol - (M opioid receptor antagonist)
71
Q

How do we treat diarrhoea?

A
  • Treat the complication
  • Treat the cause
  • Reduce bowel motility/increase transit time
  • For comfort and prevent incontinence
72
Q

How do we treat the complication of diarrhoea?

A
  • Oral rehydration
  • IV fluids
73
Q

What are some drugs that treat diarrhoea?

A
  • Opioids: codeine, loperamide
  • Muscarinic antagonists
74
Q

What is the mechanism of action of loperamide?

A
  • Decreases tone of longitudinal and circular smooth muscle
  • Reduces peristalsis but increases segmental contractions
  • Decreases colonic mass movement by suppressing gastrocolic reflex
75
Q

What do opioids target?

A
  • M and D receptors?
76
Q

What are the adverse side effects of opioids?

A
  • Paralytic ileus
  • Constipation
  • Nausea and vomiting
  • Reduced respiratory rate
  • Sedation
  • Addiction/withdrawal syndrome
77
Q

What are the contraindications of opioids?

A
  • Impaired respiratory function
  • Adrenocortical insufficiency
  • Elderly patients
78
Q

What are the adverse side effects of loperamide?

A
  • Headache
  • Nausea
  • Drowsiness
  • Dizziness
  • Dry mouth