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JL Gastrointestinal > Physiology and Pharmacology of Nausea and Emesis > Flashcards

Physiology and Pharmacology of Nausea and Emesis Flashcards

1
Q

What is an eversive experience that often precedes/accompanies vomiting, but is not simply the result of low level stimulation that, if stronger, would evoke the vomiting response?

A

Nausea

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2
Q

What can pregnancy-induced nausea and vomiting, during the first trimester be viewed as?

A

An adpative advantage

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3
Q

When vomiting, what are the stomach, oesophagus and associated sphincters doing?

A

Relaxed

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4
Q

What part of the brain co-ordinates vomiting?

A

Vomiting centre in the medulla oblongata of the brain stem

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5
Q

During the vomiting response, what occurs after suspension of intestinal slow wave activity?

A

Retrograde contractions from ileum to stomach

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6
Q

During the vomiting response, what occurs after retrograde contractions from ileum to stomach?

A

Suspension of breathing (closed glottis)

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7
Q

What occurs after suspension of breathing in the vomiting response?

A

Relaxation of LOS - contraction of diaphragm and abdominal muscles compress stomach

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8
Q

What is occurs after profuse salivation, sweating, elevated heart rate and the sensation of nausea?

A

Vomiting

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9
Q

In nausea, what does tension in gastric and oesophageal muscles trigger?

A

Afferent nerve impulses

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10
Q

In induced vomiting, what two things lead to the stimulation of enterochromaffin cells in mucosa?

A
  1. Toxic materials in gut lumen

2. Systemic toxins

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11
Q

Once enterochromaffin cells in the mucosa have been stimulated, what do they release?

A

Mediators 5-HT

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12
Q

In vomiting, what does release of 5-HT from enterochromaffin cells in the mucosa cause?

A

Depolarisation of sensory afferent terminals in mucosa (via HT3 receptors)

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13
Q

In induced vomiting, what happens after depolarisation of sensory afferent terminals in mucosa via HT3 receptors?

A

Action potential discharge in vagal afferents to brainstem (CTZ and NTS)

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14
Q

Where is the chemoreceptor trigger zone found (CTZ)?

A

In the area postrema (AP)

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15
Q

What signals through vestibular nuclei to the CTZ and then to VC in brain to coordinate vomiting?

A

Vestibular system (e.g. motion ickness)

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16
Q

How does stimuli within the CNS (e.g. pain, repulsive sights and odours, fear, anticipation and psychological factors) create vomiting?

A

Signal through cerebral cortex, limbic system, then medulla to coordinate response at VC

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17
Q

What do endogenous toxins and drugs stimulate?

A

CTZ

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18
Q

What does CTZ lack?

A

Blood brain barrier

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19
Q

Where is motor output that coordinates vomiting located in?

A

The brainstem

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20
Q

What is the vomiting centre, and what is it driven by?

A

Group of interconnected neurones within the medulla. Driven by a central pattern generator (CPG) that in turn receives input from the NTS

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21
Q

What do vagal efferents do to the oesophagus, stomach and small intestine?

A

Oesophagus - shortening
Stomach - proximal relaxation
Small intestine - giant retrograde contraction

22
Q

What two functions do the somatic motor neurones facilitate?

A
  1. Anterior abdominal muscle contraction

2. Diaphragm contraction

23
Q

What do autonomic/somatic efferents do to the heart, salivary glands, skin and sphincters of bladder and anus?

A

Heart - increase rate and force
Salivary glands - increase secretion
Skin - pallor, cold sweating
Sphincters - constriction

24
Q

As a result of vomiting, what does loss of gastric protons and chloride cause?

A

Hyperchloraemic metabolic alkalosis

25
Q

What happens to potassium levels during vomiting?

A

Hypokalaemia. Mediated by the kidney, proton loss is accompanied by potassium excretion.

26
Q

What do chemotherapy (cisplatin, doxorubicin) and radiotherapy cause, that brings on vomiting?

A

Release of 5-HT and substance P from enterochromaffin cells in the gut

27
Q

Where are Dopamine D2 receptors prevelant?

A

In the CTZ

28
Q

What is levodopa used in, that can cause vomiting?

A

Parkinsons

29
Q

Name a cardiac glycoside that can cause vomiting?

A

Digoxin

30
Q

What is a major class of anti-emetic drugs?

A

5-HT3 receptor antagonists - ‘setrons’

31
Q

What are ondansetron and palonosetron?

A

5-HT3 receptor antagonists

32
Q

How do 5-HT3 receptor antagonists work?

A

They block peripheral and central 5-HT3 receptors (cation selective channels)

33
Q

During subsequent treatments of 5-HT3 receptor antagonists, what two drugs can be added to improve response?

A

Corticosteroid

Neurokinin (NK1) receptor antagonist

34
Q

What drugs are not effective against motion sickness, or vomiting induced by agents increasing dopaminergic transmission?

A

5-HT3 receptor antagonists

35
Q

What are two side effects of 5-HT3 receptor antagonists?

A

Constipation and headaches

36
Q

What class of drugs are used for the prophylaxis and treatment of motion sickness?

A

Muscarinic acetylcholine receptor antagonists (e.g. hyosine/scopolamine)

37
Q

At what three sites do muscarinic acetylcholine receptor antagonists (e.g. hyosine.scopolamine) block?

A

Vestibular nuclei
NTS
Vomiting centre

38
Q

Give 4 side effects of muscarinic acetylcholine receptor antagonists (e.g. hyosine/scopolamine)?

A
  1. Blurred vision
  2. Urinary retention
  3. Dry mouth
  4. Centrally mediated sedation
39
Q

What class of drugs are used for prophylaxis and treatment of motion sickness and acute labyrinthitis and nausea and vomiting caused by irritants in the stomach?

A

Histamine H1 receptor antagonists (e.g. cyclizine, cinnarizine)

40
Q

Name two histamine H1 receptor antagonists?

A

Cyclizine

Cinnarizine

41
Q

What are the two locations of H1 receptors that histamine H1 receptor antagonists block?

A

Vestibular nuclei

NTS

42
Q

Give a side effect of histamine H1 receptor antagonists?

A

Drowsiness

43
Q

What class of drugs are used for drug-induced vomiting, chemotherapy, treatment of parkinsons disease and GI disorder vomtiing?

A

Dopamine receptor antagonists

44
Q

Name two dopamine receptor antagonists?

A

Domperidone and metoclopramide

45
Q

What structures do dopamine receptor antagonists peripherally exert a prokinetic action on?

A

Oesophagus, stomach and instestine

46
Q

Does domperidone cross the blood brain barrier?

A

No

47
Q

What are phenothiazines used for?

A

Severe nausea nad vomiting

48
Q

Name a NK1 receptor antagonist?

A

Aprepitant

49
Q

What are NK1 receptor antagonists used in combination with?

A

5-HT3 receptor antagonist and dexamethasone

50
Q

Name a cannabindoid (CB1) receptor antagonist?

A

Nabilone

51
Q

What drug is used for treating cytotoxic chemotherapy that is unresponsive to other anti-emetics?

A

Nabilone (cannabinoid CB1 receptor antagonists)

52
Q

What side effects are there of Nabilone?

A

Drowsiness, dizziness, dry mouth, mood changes are commo

JL Gastrointestinal (33 decks)

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