Physiology and Pharmacology of Nausea and Emesis

Question 1

nausea

Answer 1

subjective, highly unpleasant, sensation

normally felt in throat and stomach as a ‘sinking’ sensation

Question 2

acute nausea

Answer 2

mental and physically activity often relieved by vomiting

Question 3

chronic nausea

Answer 3

greatly debilitating

Question 4

signs and symptoms of nausea

Answer 4

pallor
sweating
excessive salivation

relaxation of the stomach and lower oesophagus

upper intestinal contractions, forcing intestinal contents by reverse peristalsis into the stomach

Question 5

nausea and vomiting

Answer 5

can occur in isolation

Question 6

retching

Answer 6

rhythmic reverse peristalsis of the stomach and oesophagus

forceful, involuntary contraction of abdominal muscles and the diaphragm
cardiac portion of stomach pushed into the thorax

upper intestinal contractions, forcing intestinal contents by reverse peristalsis into the stomach

pallor, sweating, excessive salivation (protective against vomit)

‘dry’

Question 7

vomiting = emesis

Answer 7

forceful expulsion of gastric/intestinal contents out of the mouth

Question 8

overall events of vomiting

repeated

Answer 8

suspension of intestinal slow wave activity

retrograde contractions from ileum to stomach

suspension of breathing (closed glottis - prevents aspiration)

relaxation of LOS-contraction of diaphragm and abdominal muscles compresses stomach

ejection of gastric contents through open UOS

Question 9

OS

Answer 9

oesophageal sphincter

Question 10

coordination of vomiting

Answer 10

by the vomiting centre (VC) in the medulla oblongata of the brain stem

VC = group of interconnected neurones within the medulla that are driven by a central pattern generator (CPG) that in turn receives input from the NTS

Question 11

stimuli inducing vomit

Answer 11

toxic materials in gut lumen

systemic toxins

Question 12

enterochromaffin cells in mucosa

Answer 12

stimulated by stimuli

release mediators -
5-HT

causes depolarisation of sensory afferent terminals in mucosa -
via 5-HT3 receptor

acts on vagus nerve
action potential discharge in vagal afferents to brain stem

co-ordination of vomiting by the ‘vomiting centre’

Question 13

vomiting reflect

Answer 13

important areas

chemoreceptor trigger zone within the area postrema

nucleus tractus solitarius

Question 14

absorbed toxic materials and drugs in blood

Answer 14

stimulate

CTZ within the AP of brainstem (lacks an effective blood brain barrier (BBB))

Question 15

mechanical stimuli

Pathological within the GI tract or other visceral organs

Answer 15

stimulate

vagal afferents to brainstem (CTZ and NTS)

Question 16

vestibular system

motion sickness

Answer 16

signalling through …

vestibular nuclei

CTZ

Question 17

stimuli within the CNS

pain, repulsive sights and odours, fear anticipation, psychological factors

Answer 17

signalling through …

cerebral cortex, limbic system

medulla

Question 18

motor outputs in vomiting

Answer 18

located in the brainstem

Question 19

vagal efferents

Answer 19

oesophagus (shortening)
stomach (proximal relaxation)
small intestine (giant retrograde contraction)

Question 20

somatic motor neurons

Answer 20

anterior abdominal muscle (contraction)

diaphragm (contraction)

Question 21

autonomic/somatic effects

Answer 21

heart - increase rate and force
salivary glands - increased secretion
skin - pallor, sold sweating

sphincters of bladder and anus - constriction

Question 22

consequences of severe vomiting

Answer 22

dehydration

loss of gastric protons and chloride - causes hypochloraemic metabolic alkalosis, raising of blood pH

hypokalaemia
mediated by the kidney, proton loss is accompanied by potassium excretion

rarely loss of duodenal bicarbonate may cause metabolic acidosis

rarely oesophageal damage

Question 23

major classes of antiemetic drugs

Answer 23

5-HT3 receptor antagonists
(-setrons)

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

block peripheral and central 5-HT3 receptors

Question 24

miscarinic acetylcholine receptor antagonists

hyoscine/scopolamine

Answer 24

used for prophylaxis and treatment of motion sickness

probably block muscarinic acetylcholine receptors at multiple sites

direct inhibition of GI movements and relaxation fo the GI tract may contribute (modestly) to antiemetic effects

unwanted effects from blockage of the parasympathetic ANS
blurred vision, uriniary retention, dry mouth

Question 25

histamine H1 receptor antagonist

cyclizine

Answer 25

used for prophylaxis and treatment of motion sickness and acute labyrinthitis and nausea and vomiting caused by irritants in the stomach

less effective against substances that act directly on CTZ

action attributed to blockage of H1 receptors in vestibular nuclei and NTS

generally cause CNS depression and sedation - drowsiness may affect performance of skilled tasks