Physiology and Pharmacology of Nausea and Vomiting Flashcards
what is nausea?
unpleasant urge to vomit
felt in throat and stomach as sinking feeling
what can acute nausea affect?
mental and physical activity
what is chronic nausea?
prolonged sensation of nausea
greatly debilitating
what does nausea involve?
autonomic: pallor, excessive salivation, relaxation of stomach and lower oesophagus
upper intestinal contraction (duodenum and jejunum), forcing contents into stomach by reverse peristalsis through open pyloric sphincter
nausea and vomiting always occur together, true or false?
false
either can occur in isolation
what is retching?
rhythmic reverse peristalsis of the stomach and oesophagus without vomiting
forecfull involuntary contraction of abdominal muscles and diaphragm (can push cardiac portion of the stomach into the thorax)
Upper intestinal contractions forcing intestinal contents into stomach via reverse peristalsis
what are the autonomic symptoms of retching?
pallor
sweating
excessive salivation (neutralises acidic contents of chyme entering oesophagus)
what is vomiting?
emesis
forceful expulsion of gastric/intestinal contents through mouth/nose by contraction of abdominal muscles and diaphragm
what are the steps involved in vomiting?
suspension of intestinal slow wave activity > retrograde contractions from ileum to stomach > suspension of breathing (closed glottis) > relaxation of LOS, contraction of diaphragm and abdominal muscles compress stomach > ejection of gastriccontents through open UOS > repeat cycle
does vomiting involve the act of contraction of the stomach?
no
increased intra-abdominal pressure due to contraction of skeletal muscle compresses stomach
what autonomic symptoms precede vomiting?
salivation, sweating, elevated heart rate
what co-ordinates vomiting?
vomiting centre in the medulla
what stimuli can cause vomiting?
presence of toxic materials in the gut lumen systemic toxins (cytotoxic drugs)
what cells do vomiting stimuli stimulate?
enterochromaffin cells in mucosa
what do enterochromaffin cells do?
release 5-HT (serotonin) and substance P which depolarize sensory afferent termianls in mucosa via activated 5-HT receptors
what happens when sensory afferent terminals in mucosa are depolarized?
action potential discharged into vagal afferents to brainstem (CTZ and NTS)
what are CTZ and NTS and what do they do?
CTZ = chemoreceptor trigger zone within the area postrema (AP)
NTS = nucleus tractus solitaries
Co-ordination of vomiting by the ‘vomiting centre’
what non toxic factors can cause vomiting?
motion sickness
anxiety
etc
why can an MI cause vomiting?
stimulation of …
intense pain
what is anticipatory vomiting?
eg. chemo patient vomiting at the sight of a hospital
CNS stimulation
what gives rise to motion sickness?
difference between stimuli from eyes and body movement
where is the motor output that coordinates vomiting located?
in the brainstem
what is the vomiting centre?
group of interconnected neurones within the medulla driven by central pattern generator(CPG) that receives input from the NTS
what are the 3 branches of motor output?
vagal efferents
Somatic motor neurons
Autonomic/somatic efferents
what do vagal efferents (autonomic NS) do?
giant retrograde contraction of small intestine
proximal relaxation of stomach
shortening of oesophagus
what do somatic motor neurones do?
anterior abdominal muscle contraction
diaphragm contraction
what do joint autonomic/somatic efferents do?
immediately precede vomiting (prodromal signs)
- increased HR and force
- increased saliva secretion
- pallor, cold sweating
also constrict sphincters of bladder and anus
list 5 possible consequences of severe vomiting
dehydratin
hypochloraemic metabolic alkalosis (loss of gastric protons and chloride)
Metabolic acidosis (rare)
Hypokalaemia
Mallory-Weiss tear (tear in inner mucosal walls of oesophagus - streaks of fresh blood in vomit)
aspiration of the vomitus
what classes of drug can cause nausea and vomiting?
cancer chemotherapy and radiotherapy
General anaesthetic
Agents with dopamine agonist properties (lots of dopamine receptors in CTZ)
Morphine and other opiate analgesics (tolerance develops)
cardiac glycosides (eg. digoxin)
Drugs enhancing 5-HT function (anti-depressants)
what are 5-HT receptor antagonists (setrons)?
antiemetic drugs (ends in setron) supress chemo/radiotherapy and post-op induced nausea and vomiting
how do 5-HT receptor antagonists work?
block peripheral and central 5-HT receptors
when are 5-HT receptor antagonists less effective?
during subsequent treatments
what can improve the action of a 5-HT receptor antagonist?
addition of a corticosteroid and a neurokinin (NK1) receptor antagonist
what are 5-HT receptor antagonists not effective against?
motion sickness
..
what are muscarinic acetylcholine receptor antagonists? give 2 examples
anti-sickness drugs
hyosine
scopolamine
what are muscarinic acetylcholine receptor antagonists used for?
motion sickness treatment and prophylaxis via a transdermal patch
how do muscarinic acetylcholine receptor antagonists work?
block muscarinic muscarinic acetylcholine receptors at multible sites (NTS, vomiting centre) inhibiting GI movements and relaxation of GI tract contributing to anti-emetic effects
what are the side effects of muscarinic acetylcholine receptor antagonists?
blurred vision
urinary retention
dry mouth
what are histamine H1 receptor antagonists?
anti sickness
cyclizine
cinnarizine
what are histamine H1 receptor antagonists used for?
prophylaxis and treatment of motion sickness and acute labyrinthitis and nausea/vomiting due to stomach irritants
how do histamine H1 receptor antagonists work?
block H1 receptors in vestibular nuclei and NTS
what are the side effects of histamine H1 receptor antagonists?
CNS suppression
what are dopamine receptor antagonists?
domperidone
metoclopramide
used for drug induced vomiting and vomiting due to GI disease
are dopamine receptor antagonists used in children?
use restricted
how do dopamine receptor antagonists work?
centrally block D2 and D3 receptors in CTZ
peripherally exert a prokinetic action on oesophagus
