Physiology of Nausea and Vomiting Flashcards
What is Nausea?
sinking feeling, doesn’t necessarily lead to vomiting, pallor, excessive sweating
relaxation of the stomach and lower oesophagus, upper intestinal contractions, forcing reverse peristalsis into the stomach
What is Vomiting/Emesis?
forceful expulsion of stomach contents through the mouth/nose by contraction of the abdominal muscles and diaphragm
What is Retching?
repetitive reverse peristalsis of the stomach and oesophagus without vomiting
Forceful, involuntary contraction of the abdominal muscles and diaphragm
Increased saliva can neutralise the acid chyme coming into the oesophagus
What is Regurgitation?
the effortless movement of swallowed food contents/ stomach acid back into the mouth
What are the two stimulis for vomiting?
Systemic toxins (e.g. cytotoxic drugs) Toxic materials in gut lumen (e.g. bacterial toxins, salts of heavy metals, ethanol)
What do the two stimulus stimulate?
Enterochromaffin cells in mucosa releasing 5-HT mediators
What does the release of 5-HT mediators cause?
Depolarization of sensory afferent terminals in mucosa (e.g. via 5-HT3 receptors)
Action potential discharge in vagal afferents to brainstem (CTZ and NTS)
Co-ordination of vomiting by the ‘vomiting centre’
What are the CTZ and NTS?
CTZ - chemoreceptor trigger zone within the area postrema (AP)
NTS – nucleus tractus solitarius
What do absorbed toxic material and drugs in the blood stimulate to cause vomiting?
CTZ within the AP of the brainstem
What do mechanical stimuli, pathology within the GI tract or other viseral organs stimulate to cause vomiting?
Vagal afferents to the brainstem CTZ and NTS
What does the vestibular system (e.g. motion sickness) stimulate to cause vomiting?
CTZ
What does stimuli in the CNS like pain, odours, repulsive sites stimulate to cause vomiting?
Cerebral cortex, lumbic system - i.e. straight to the vomiting centre
What are the steps of vomiting?
- 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
- Repeats of the cycle
Vomiting does not involve stomach contractions, it is due to an increased intraabdominal pressure
What is the Vomiting centre?
a group of interconnected neurones within the medulla that receives input from the NTS
What is an efferent?
leaves the CNS and goes to peripheries
What are the autonomic/somatic efferents that preceed vomiting?
increased heart rate and force
increased salivation
pallor, cold sweating
constriction of bladder and anus
What are the vagal efferents that occur during vomiting?
Shortening of the oesophagus
Proximal relaxation of the stomach
Giant retrograde contraction of the small intestine
What are the somatic neuron effects that happen during vomiting?
diaphragm contraction
contraction of the anterior abdominal muscle
What are the consequences of severe vomiting?
Dehydration
Loss of gastric protons and chloride – causes hypochloraemic metabolic alkalosis
Metabolic acidosis may occur due to duodenal bicarbonate loss
Hypokalaemia - potassium excretion by kidneys
Aspiration of the vomitus into the air passage and lungs
Mallory-Weiss tear due to profuse vomiting that tears the inner mucosal walls of the oesophagus
What drugs and radiation can induce vomiting?
cancer chemotherapy (cisplatin, doxorubicin) and radiotherapy. Chemotherapy drugs release 5-HT and substance P from enterochromaffin cells in the gut
Operations involving the administration of general anaesthetic (post operative nausea and vomiting)
Levodopa used in Parkinson disease (dopamine agonist properties have a high density of D2 receptors which are prevalent in the CTZ)
Morphine and other opiate analgesics
Cardiac glycosides (digoxin)
Drugs enhancing 5-HT function – SSRIs, 5HT, receptors prevalent in the CTZ)
What are the major classes of anti-emetic drugs?
Dopamine antagonists 5HT3-Receptor Antagonists Muscarinic receptor antagonist H1 Antihistamines Anticholinergics Adjuvant Antiemetics Prokinetic Drugs
Describe the names and action of dopamine antagonists?
Prochlorperazine, droperidol,trifluoperazine chlorpromazine, haloperidol, levomepromazine
Choose domperidone because it cannot cross the BBB so the brain is protected and it is specific targeting
act centrally by blocking the chemoreceptor trigger zone
available as rectal suppositories, buccal tablets
Prophylaxis/treatment of nausea and vomiting associated with neoplastic disease, radiation sickness, and drug-induced emesis
Describe the names and action of 5HT3-Receptor Antagonists?
Granisetron, ondansetron, palonosetron, Setron
block 5HT3 receptors in the GIT and CNS.
Frequent side effect is constipation and headache, not effective in motion sickness
Describe the names and action of muscarinic receptor antagonists?
To treat motion sickness
Hyosine and scoplamine
Prolonged duration of action
Describe the names and action of H1 Antihistamines?
Promethazine, cyclizine, cinnarizine
Blockade of H1 receptors in vestibular nuclei and NTS Cause CNS depression and sedation
Many agents exert an additional Antimuscarinic effect that probably contributes to their activity
Useful in Motion sickness (prophylaxis and treatment) morning sickness, PONV
Describe the names and action of Anticholinergics?
Hyosine (scopolamine), Dicyclomine
Block muscarinic receptors in vestibular nuclei, NTS, vomiting centre
Motion sickness
Frequent side effects include: blurred vision, urinary retention, dry mouth, sedation
Describe the names and action of Prokinetic drugs?
GI Tract -Increase Gastric peristalsis -Increase Lower Esophageal sphincter tone CNS - blocks D2 receptors in CTZ
Metoclopramide (antiemetic, GORD, Migraine)
Domperidone (does not cross the blood-brain barrier)
Name some Ajuvant Antiemetics?
Role in CINV NK1 receptor antagonists - antagonism of substance P Corticosteroids - Dexamethasone, methylprednisolone - Augmentate the effect of ondansetron & metoclopramide Benzodiazepines - Lorazepam, diazepam - No intrinsic antiemetic action - Sedative, antianxiety, amnesia inducing effect Cannabinoids - Nabilone, Dronabinol - Sedation, Hallucinogenic, dry mouth
