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LC Gastroenterology Week 3 > Physiology and Pharmacology of nausea and vomiting > Flashcards

Physiology and Pharmacology of nausea and vomiting Flashcards

1
Q

What is nausea?

A

The unpleasant urge to vomit- not the actual act of vomiting

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2
Q

What is vomiting/emesis?

A

The forceful expulsion of stomach contents through the mouth/nose by contraction of the abdominal muscles and diaphragm

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3
Q

What is retching?

A

repetitive reverse peristalsis of the stomach and oesophagus without vomiting. (usually follows vomiting)

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4
Q

What is regurgitation?

A

is the effortless movement of swallowed food contents/ stomach acid back into the mouth (not associated with nausea or retching, no vomiting).

Effortless reflux of the gastric contents

Patients - might label it as vomiting

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5
Q

What is vomiting co-ordianted by?

A

The vommitting centre in the medulla oblongata of the brain stem

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6
Q

The contraction of what muscles cause vomiting?

A

Contraction of the abdominal muscles and diaphragm

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7
Q

Is vomiting due to stomach contraction?

A

No both the stomach and oesophagus and associated sphincters are relaxed

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8
Q

What is vomiting frequently preceded by?

A

Profuse salivation, sweating (cold), elevated HR and sensation of nausea

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9
Q

What are some of the consequences of severe (repeated) vomiting?

A

Dehydration

Loss of gastric protons and chloride - causes hypochloraemic metabolic alkalosis

Hypokalaemia (reflux potassium excretion by kidneys)

Mallory-Weiss tear (due to profuse committing that tears the inner mucosal walls of the oesophagus

Aspiration of the vomitus into the air passage and lungs (sometimes glottis closure is incomplete)

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10
Q

Describe the different places in the brain that help to control vomiting?

A

Chemoreceptor trigger zone (CTZ) - drugs (chemoradiation), opioids

Nucleus tractus solitarius (NTS)

Vomiting centre (VC) - smell, thought, sight

Vestibular nuclei - motion sickness

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11
Q

What are the different types of drug types that can be used to target nausea and vomiting?

A

D2 receptor antagonists
H1 receptor antagonists
5-HT3 receptor antagonists
Muscarinic Ach receptor antagonists

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12
Q

What is the vomiting centre?

A

Main sight of neural control of vomiting

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13
Q

What is the CTZ?

A

The chemoreceptor trigger zone
Senses blood borne chemical stimuli that induces vomiting like morphine
Also stimulates the VC to induce vomiting

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14
Q

What is the vestibulocochlear/vestibular nuclei?

A

It plays a role in motion sickness and diseases of the ear, it sends signals to the VC to induce vomiting

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15
Q

Why do heart rate, sweating and salivation increase when you vomit?

A

Because the autonomic centres regulating those things are close to the VC and they are stimulated in the surge of neuronal activity that company vomiting

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16
Q

What can prolonged or profuse vomiting deplete?

A

Fluid and electrolytes - leading to dehydration and changes in the blood chemistry

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17
Q

What is the mechanism of muscarinic ACh receptor antagonists? (Anticholinergics)

A

Block muscarinic receptors in the vestibular nuclei, NTS and VC

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18
Q

What are muscarinic ACh receptor antagonists used in?

A

Motion sickness mostly

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19
Q

What are the side effects of muscarinic ACh receptor antagonists?

A

Blurred vision
Urinary retention
Dry mouth

All due to blockage of the parasympathetic ANS

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20
Q

How might you administer muscarinic ACh receptor antagonists?

A

Transdermal patch, Oral, IM

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21
Q

What are adjuvant antiemetics?

A

They are given with standard emetics to enhance their effect

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22
Q

What are some examples of adjuvant antiemetics?

A

Corticosteroids
Benzodiazepines - can cause a sedative affect preventing vomiting etc
Cannabinoids
NK1 receptor antagonists

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23
Q

Describe the treatment of chemotherapy-induced Nausea and vomiting (CINV)

A

Triple drug therapy

  • 5HT3 receptor antagonist
  • dexamethasone - corticosteroid
  • aprepitant - NK1 receptor antagonists
24
Q

Describe the mechanism of Histamine H1 receptor antagonists?

A

blockade of H1 receptors in vestibular nuclei and NTS

Some may also block muscarinic receptors - contributing to their effectiveness

25
Q

What are H1 receptor antagonists used for?

A

Motion sickness
Vomiting and nausea - esp related to irritants within the stomach
morning sickness
Post op nausea and vomiting

Less effective against substances that act directly on the CTZ

26
Q

What are some of the side effects of H1 receptor antagonists

A

Depression
Drowsiness
Sedation

27
Q

Describe the mechanism of Dopamine D2 receptor antagonists?

A

Centrally block dopamine D2 (and D3) receptors in the CTZ

Peripherally exert a pro kinetic (enhances gastric motility) action on the oesophagus, stomach and intestine - some

28
Q

What are Dopamine D2 receptor antagonists used in?

A

Drug induced vomiting
Vomiting in GI disorders

Not effective against motion sickness

29
Q

What are some examples of H1 receptor antagonists?

A

Cyclizine Cinnarazine Promethazine

30
Q

What are some examples of D2 receptor antagonists?

A

domperidone

metoclopramide

31
Q

Why might domperidone be more beneficial that metoclopramide?

A

It cannot cross the BBB and thus wont produce the same side effects as metoclopramide such as disorders of movement

32
Q

Describe the mechanism of action of 5-HT3 receptor antagonists?

A

Block peripheral and central 5-HT3 receptors (in the GI Tract as well as the CNS)

33
Q

What are some examples of 5-HT3 receptor antagonists?

A

Ondansetron
Palonosetron
Granisetron

34
Q

Describe when you would use 5-HT3 receptor antagonists?

A

Used to suppress chemotherapy- and radiation-induced emesis and post-operative nausea and vomiting

35
Q

What is associated with the VC?

A

Sight, smell and thought

36
Q

What is associated with the CTZ?

A

Cancer chemotherapy

Opioids

37
Q

What is associated with the vestibular nuclei?

A

Motion sickness

38
Q

What drugs will work on the CTZ?

A

Dopamine antagonists

5-HT3 antagonists

39
Q

What drugs will work on the VC and the vestibular nuclei?

A

H1 antagonist

Antimuscarinc drugs

40
Q

What are the side effects of 5HT-3 antagonists?

A

Generally well tolerated

Constipation and headaches

41
Q

Describe the mechanism of NK1 receptor antagonists?

A

antagonism of substance P (which causes vomiting and is released by vagal afferents) is assumed

42
Q

What are NK1 receptor antagonists used in?

A

Used in combination with a 5-HT3 receptor antagonist and dexamethasone in the acute phase of highly emetogenic chemotherapy. In combination with dexamethasone in the delayed phase

43
Q

Give an example of an NK1 receptor antagonist?

A

aprepitant

44
Q

What is the mechanism of Cannabinoid (CB1) receptor agonists?

A

Decreases vomiting induced by agents stimulating the CTZ. Evidence suggests that opiate receptors are involved in drug effect

45
Q

What are Cannabinoid (CB1) receptor agonists used in?

A

Used ideally in in-patient setting for treatment of cytotoxic chemotherapy that is unresponsive to other anti-emetics

46
Q

What are some side effects of cannabinoids?

A

drowsiness, dizziness, dry mouth, mood changes are common

47
Q

Give an example of an cannabinoid?

A

nabilone

48
Q

What is located in the brainstem?

A

The major output that coordinates vomiting

49
Q

Descrive what the vagal efferents do in terms of motor output?

A

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

50
Q

Describe what the somatic motor neurones do in terms of motor output?

A

Diaphragm - contracts

Anterior abdominal muscles - contract

51
Q

Describe what the autonomic/somatic efferents to in terms of motor output?

A

Increases HR and force
Increases salivation
Skin - pallor, cold, sweating
Sphincters of bladder and anus - contraction

52
Q

Describe what causes pregnancy associated nausea and committing?

A

Caused by human chorionic gonadrotropin (HCG) produced by the placenta

53
Q

What treatment might you offer for pregnancy associated nausea and vomiting?

A

Non pharmacological treatments

  • changes in diet
  • use of ginger or pyridoxine
  • wrist (P6) acupressure
54
Q

What is hyperemesis gravidarum?

A

Fluid and electrolyte disturbances or nutritional deficiency developing from intractable vomiting in pregnancy

55
Q

What would you use to treat hyperemesis gravidarum?

A

First line - antihistamine (promethazine or cyclizine)

Second line - prochlorperazine and metoclopramide

56
Q

What can metoclopramide do specifically?

A

Has unique properties of increasing lower esophageal sphincter pressure and increasing the rate of gastric emptying.

Used to treat: antiemetic, migraine, GORD

LC Gastroenterology Week 3 (15 decks)

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