Lecture 18 - Nausea/vomiting Constiption And Diarrhoea Flashcards

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1
Q

What is vomiting/emesis?

A

Invlountary, forceful expulsion of gastric contents through the mouth

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2
Q

Where is the vomiting centre located in the brain?

A

Medulla

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3
Q

What is the very general process of vomiting?

A

Deep breath
Glottis closes
Abdo muscles contract (inc Intra abdominal pressure)
Lower oesophageal sphincter relaxes
Retrograde peristalsis of small bowels

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4
Q

What is regurgitation?

A

Often seen in babies
When some feed gets brought back up

Not the same as vomiting

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5
Q

What are the receptors that are found in the vomiting centres in the medulla?

A

Muscarinic ACh
H1(Histamine receptor)
5HT2 (type of serotonin receptor)
NK1 (Neurokinin 1)

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6
Q

What are some stimuli from the cortical centres that may activate the vomiting centre in the medulla?

A

Pain
Visual stimuli
Smells
Stress

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7
Q

How do we manage vomiting or nausea?

A

Conservative management (avoid stimuli)

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8
Q

What part of the brain is stimulated when motion sickness occurs?

A

Vestibular nuclei receive input from labyrinth

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9
Q

What receptors are located in the vestibular nuclei that when are activate lead to motion sickness?

A

Muscarinic ACh
Histamine 1 receptors

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10
Q

What type of drugs are given to treat motion sickness?

A

Muscuranic receptor antagonists (competitive blockers)

H1 antagonists

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11
Q

What are some examples of anti Muscarinic drugs that can be used to treat motion sickness?

A

Hyoscine hydrobromide (works centrally)

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12
Q

What are the adverse reactions of Muscarinic antagonists like hyoscine hydrobromide? (Given for motion sickness)

A

Sedation
Constipation
Dizziness
Dry mouth
Visual problems
Confusion

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13
Q

What are the contraindications for giving Muscarinic antagonists like hyoscine hydrobromide? (Given for motion sickness)

A

Elderly
Glaucoma

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14
Q

What are some importnat drug drug interactions for Muscarinic antagonists like hyoscine hydrobromide? (Given for motion sickness)

A

Anti psychotics

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15
Q

How do H1 antagonists work to treat motion sickness?

A

Works centrally, Act on vomiting centre and vestibular nuclei
Inhibiting histmainergic signals from vestibular system to the CTZ in the medulla

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16
Q

What are some examples of H1 antagonists that treat motion sickness?

A

Cyclizine
Levomepromazine

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17
Q

What are some adverse reactions of H1 antagonists?

A

Sedation
Anti-muscarinic side effects-dry mouth
Constipation
Urinary retention
Blurred vision

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18
Q

What are some contraindications of H1 antagonists?

A

Epilepsy
Glaucoma
Urinary retention
Children
Elderly

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19
Q

What are some sedating H1 antagonists?

A

Diphenhydramine
Cyclizine
Promethazine

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20
Q

What are some non sedating H1 antagonists?

A

Cetirizine (often given for hay fever/allergic rhinitis)
Fexofenadine
Loratidine

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21
Q

Who is motion sickness most common in?

A

Women. And children
Those who have migraines

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22
Q

What are some conservative managements of motion sickness?

A

Hydration
Pistioion in vehicle
Distraction

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23
Q

What are some drugs given for motion sickness?

A

Anitmuscarinics - hyoscine

Anti histamines - Cyclizine, cinnarizine, prochlorperazine

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24
Q

What are some receptors located in the CTZ?

A

D2 (dopamine)
NK1
5HT3

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25
Q

What is an example of a D2 receptor antagonist?

A

Metoclopramide

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26
Q

What affects do D2 receptor anatogonsists like metoclopramide have?

A

CENTRAL DOPAMINE ANATAGONIST BUT PERIPHERAL CHOLINERGIC AGONIST:
Inc ACh at M receptors in gut promoting gastric emptying
Inc tone at lower oesophageal sphincter ROS it closes
Inc tone and amplitude of gastric contractions
Dec tone of pyloric sphincter
Inc peristalsis

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27
Q

What are some adverse drug reactions of metoclopramide?

A

Depression
Diarrhoea
Drowsiness
Hypotension
Glactorrhoea
Extra pyramidal effects (dystopia)
Parkinsonism

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28
Q

What are some contraindications to metoclopramide?

A

Post GI surgery
Gi obstruction
Gi perforation
GI haemorrhage

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29
Q

What is the D2 receptor antagonist domperidone good for?

A

Improving lactation in breastfeeding mothers

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30
Q

What are the adverse effects of domperidone?

A

Dry mouth
Long QT and VT (cardiac side effects)
Loss of libido

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31
Q

What are some contraindications of domperidone?

A

Patients over 60 with arrhythmias

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32
Q

What is an example of a D2 receptor antagonist which is an anti-psychotic?

A

Haloperidol

Prochlorperazine, chlorpromazine

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33
Q

What part of the brain does Haloperidol act on?

A

CTZ

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34
Q

What are the adverse drug reactions of haloperidol?

A

Parkinsonism
Movement disorders
Long QT
Arrhythmias
Constipation
Dry mouth

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35
Q

What are the contraindications to Haloperidol?

A

Parkinson’s disease
Cardiovascular disease]]
Diabetes
Myasthenia gravis

36
Q

What are some adverse reactions of prochlorperazine, chlorpromazine or levomepromazine?
Haloperidol is also in this category
What type of drugs are these?

A

D2 receptor antagonists that are. Antipsychotics

Drowsiness
Dry mouth
Movemtn disorders
Parkinsonism
Long QT
Urinary retention

37
Q

What are some contraindications of prochlorperazine, chlorpromazine or levomepromazine?
(D2 receptor antagonists which are antipsychotics) + Haloperidol

A

Elderly patient
Parkinson’s disease
Cardiovascular disease
Diabetes
Myasthenia gravis

38
Q

What is the function of NK-1 (neurokinin) receptor antagonists?

A

Prevents action of substance P at the CTZ and in peripheral nerves

Boosts effects of 5HT3 (serotonin) receptor antagonists

39
Q

When are NK-1 receptor antagonists typically used?

A

Good for chemotherapy particularly for delayed emesis

Also has anxiolytic and antidepressant properties

40
Q

What are some examples of NK-1 receptor antagonists?

A

Aprepitant
Fosaprepitant
Netupitant

41
Q

What are some adverse reactions of NK-1 receptor antagonists?

(Aprepitant)

A

Constipation
Headache
Asthenia (weakness not related to lack of sleep)

42
Q

What is the contrainidaiction for Nk-1 receptor antagonists?

Aprepitant

A

Acute porphyrias (conditions affecting enzymes involved in haem synthesis)

43
Q

What part of the brain do corticosteroids act on?

A

CTZ

But may also have properties of D2 receptor antagonists

44
Q

What types of vomiting are corticosteroids good for?

A

Perioperative nausea and vomiting
Chemotherapy related vomiting
Palliative vomiting

45
Q

What are some examples of corticosteroids used for anti emetics?

A

Dexamethosome
Methylprednisolone

46
Q

What are some adverse effects of corticosteroids? (Dexamethasome and methylprednisolone)

A

Insomnia
Osteoporosis
Inc weight
Inc appetite
Inc blood sugar
Cushing’s syndrome

47
Q

What are some contraindications to using corticosteroids for anti-emetics?

A

Osteoporosis
Diabetes Mellitus
Peptic ulcers

48
Q

Where do cannabinoids act?

A

CTZ

Last line use for chemotherapy

49
Q

What are the adverse drug reactions to cannabinoids?

A

Confusion
Depression
Drowsiness
Dizziness
Movement disorders
Psychosis
Tremor
Visual impairment

50
Q

What are the contraindications to cannabinoids?

A

Elderly patients
Heart disease
Hx of psychiatric disorder

51
Q

what is an example of a cannabinoid?

A

Nabilone

52
Q

What are some metabolic causes of post-operative vomitting?

A

Uraemia
DKA
Hypercalcaemia

53
Q

What are some potential drugs used to treat post-operative vomiting?

A

Metoclopramide
Hyoscine (anti-Muscarinic)

54
Q

What is ileus?

A

Condition caused by lack of movemtn of smooth muscle in the intestine leading to obstructions and blockages

55
Q

What are the first things you do when treating pregnancy induced vomiting? (Hyperemesis gravidarum)

A

Fluids replacement

Anti-histamines (promethazine/cyclizine)
Phenothiazine - prochlorperazine
Ondansetron
Steroids
Metoclopramide

Thiamine replacetn

56
Q

What part of the vomiting pathway is involved in nausea and vomiting involving gut problems?

A

Enterochromaffin cells (toxic chemicals in gut)

Vagal afferents (convery signals from gut to brainstem)

57
Q

What receptors are stimulated with GI problems in the enterochromaffin cells and vagal afferents leading to nausea or vomting?

A

D2 (dopamine)
NK1 (neurokinin 1)
5HT3 (serotonin)

58
Q

What is the main category of drug that is used to treat nausea/vomitng due to GI problems and why?

A

5-HT3 antagonists (serotonin)

Most serotonin receptors are found in the gut

59
Q

When is serotonin produced in the gut and what is its action?

A

Made by enterochromaffin cells in response to parasympathetic stimulation
Serotonin excites enteric neurones increasing gut motility, increasing gut secretions and regulates appetite

60
Q

What is an example of a 5-HT3 antagonist to treatGI vomitting?

A

Ondansetron

61
Q

What are the central and peripheral effects of a 5-HT3 (serotonin) antagonist?

What is an example of this drug?

A

Ondansetron

Peripherally = reduces gut motility and reduces gut secretions

Centrally = Inhibits CTZ

62
Q

What are the adverse reactions of Ondansetron (5-HT3 antagonists)?

A

Constipation
Headache
Elevated liver enzymes
Long QT syndrome
Extra-pyramidal effects (dystonia)
Parkinsonism

63
Q

What are the contraindications of 5-HT3 antagonists (Ondansetron)?

A

Subacute abdominal obstruction
Susceptible to long QT

64
Q

What is the 1st line drug treatment for an anti-emetic when a patient has a bowel obstruction?

A

Cyclizine

65
Q

How do you non pharmacologically treat bowel obstruction?

A

NG tube

66
Q

Go to slide 34 and label the pathway

A
67
Q

What is considered constipation?

A

Change in consistency and reduced frequency of stools

68
Q

How is constipation managed before drugs?

A

Healthy diet (dietary fibre intake)
Fluid intake
Exercise
Toilet routing and positioning

69
Q

What is fecal impaction?

A

When theres a hardened bit of stool blocking the rectum or colon preventing faeces from being passed

70
Q

How do bulk-forming laxatives work?

A

Polysaccharide polymers (acting like fibre) dont get digested

So increases the oncotic pressure in teh gut lumen promoting peristalsis and improving faecal consistency

71
Q

What are some examples of bulk-forming laxatives?

A

Isphagula husk
Methyl cellulose

72
Q

What are some examples of faecal softeners?

A

Sodium docusate
Arachis oil enema
Liquid paraffin

73
Q

What are some examples of osmotic laxatives?

A

Lactulose
Macrogol

74
Q

How do osmotic laxatives work?

A

Laxatives poorly absorbed in the gut so increase oncotic potential in gut drawing water in

75
Q

How do laxative stimulants work?

A

Increasing electrolyte and water secretion by the mucosa and by increasing peristalsis by stimulating enteric nerves

76
Q

What are some examples of laxative stimulants?

A

Bisacodyl
Sodium picosulfate
Senna
Glycerol suppositories

77
Q

What are some drug causes of diarrhoea?

A

Domperidone (increases GI motility)
Metoclopramide (increases gastric emptying and motility)
Naloxegol (Mu opioid antagonist that is similar to Naloxone)

78
Q

What are some causes of diarrhoea?

A

Infection (Cholera)
Toxins/drugs
Radiotherapy
Anxiety

79
Q

How do you treat diarrhoea?

A

Treat the complication:
-oral rehydration
-IV fluids

Treat the cause:
-travellers diarrhoea
-campylobacter
-salmonella

Reduce bowel motility and increase transit time

80
Q

What are some drugs used to treat diarrhoea?

A

Opioids
Loperamide

81
Q

How do opioids work to treat diarrhoea?

A

Agonises Mu opioid and delta receptors

Side effect is constipation (its a secondary action)

82
Q

What are some adverse reactions of opioids?

A

Paralytic ileus
Constipation
Nausea and vomitng
Reduced Respiraoty rate (RESP DEPRESSION)
Sedation
Addiction and withdrawal syndromes

83
Q

What are some contraindications of opioids?

A

Impaired resp function
Adrenocortical insufficiency
Elderly patients

84
Q

How does loperamide work to treat diarrhoea?

A

A type of Mu opioid receptor agonsit
Binds specifically to the Mu opioid receptors in the Myenteric plexus

Decreases tone of longitudinal and circular smooth muscle
Reduces peristalsis but increases segmental contractions
Decreases colonic mass movement by suprresing gastrocolic reflex

85
Q

What are the adverse reactions of loperamide?

A

Headache
Nausea
Drowsiness
Dizziness
Dry mouth

86
Q

What are the contraindications of loperamide?

A

Abdominal pathologies
Children under 12