Flashcards in Physiology and Pharmacology of Nausea and Emesis Deck (52):
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?
What can pregnancy-induced nausea and vomiting, during the first trimester be viewed as?
An adpative advantage
When vomiting, what are the stomach, oesophagus and associated sphincters doing?
What part of the brain co-ordinates vomiting?
Vomiting centre in the medulla oblongata of the brain stem
During the vomiting response, what occurs after suspension of intestinal slow wave activity?
Retrograde contractions from ileum to stomach
During the vomiting response, what occurs after retrograde contractions from ileum to stomach?
Suspension of breathing (closed glottis)
What occurs after suspension of breathing in the vomiting response?
Relaxation of LOS - contraction of diaphragm and abdominal muscles compress stomach
What is occurs after profuse salivation, sweating, elevated heart rate and the sensation of nausea?
In nausea, what does tension in gastric and oesophageal muscles trigger?
Afferent nerve impulses
In induced vomiting, what two things lead to the stimulation of enterochromaffin cells in mucosa?
1. Toxic materials in gut lumen
2. Systemic toxins
Once enterochromaffin cells in the mucosa have been stimulated, what do they release?
In vomiting, what does release of 5-HT from enterochromaffin cells in the mucosa cause?
Depolarisation of sensory afferent terminals in mucosa (via HT3 receptors)
In induced vomiting, what happens after depolarisation of sensory afferent terminals in mucosa via HT3 receptors?
Action potential discharge in vagal afferents to brainstem (CTZ and NTS)
Where is the chemoreceptor trigger zone found (CTZ)?
In the area postrema (AP)
What signals through vestibular nuclei to the CTZ and then to VC in brain to coordinate vomiting?
Vestibular system (e.g. motion ickness)
How does stimuli within the CNS (e.g. pain, repulsive sights and odours, fear, anticipation and psychological factors) create vomiting?
Signal through cerebral cortex, limbic system, then medulla to coordinate response at VC
What do endogenous toxins and drugs stimulate?
What does CTZ lack?
Blood brain barrier
Where is motor output that coordinates vomiting located in?
What is the vomiting centre, and what is it driven by?
Group of interconnected neurones within the medulla. Driven by a central pattern generator (CPG) that in turn receives input from the NTS
What do vagal efferents do to the oesophagus, stomach and small intestine?
Oesophagus - shortening
Stomach - proximal relaxation
Small intestine - giant retrograde contraction
What two functions do the somatic motor neurones facilitate?
1. Anterior abdominal muscle contraction
2. Diaphragm contraction
What do autonomic/somatic efferents do to the heart, salivary glands, skin and sphincters of bladder and anus?
Heart - increase rate and force
Salivary glands - increase secretion
Skin - pallor, cold sweating
Sphincters - constriction
As a result of vomiting, what does loss of gastric protons and chloride cause?
Hyperchloraemic metabolic alkalosis
What happens to potassium levels during vomiting?
Hypokalaemia. Mediated by the kidney, proton loss is accompanied by potassium excretion.
What do chemotherapy (cisplatin, doxorubicin) and radiotherapy cause, that brings on vomiting?
Release of 5-HT and substance P from enterochromaffin cells in the gut
Where are Dopamine D2 receptors prevelant?
In the CTZ
What is levodopa used in, that can cause vomiting?
Name a cardiac glycoside that can cause vomiting?
What is a major class of anti-emetic drugs?
5-HT3 receptor antagonists - 'setrons'
What are ondansetron and palonosetron?
5-HT3 receptor antagonists
How do 5-HT3 receptor antagonists work?
They block peripheral and central 5-HT3 receptors (cation selective channels)
During subsequent treatments of 5-HT3 receptor antagonists, what two drugs can be added to improve response?
Neurokinin (NK1) receptor antagonist
What drugs are not effective against motion sickness, or vomiting induced by agents increasing dopaminergic transmission?
5-HT3 receptor antagonists
What are two side effects of 5-HT3 receptor antagonists?
Constipation and headaches
What class of drugs are used for the prophylaxis and treatment of motion sickness?
Muscarinic acetylcholine receptor antagonists (e.g. hyosine/scopolamine)
At what three sites do muscarinic acetylcholine receptor antagonists (e.g. hyosine.scopolamine) block?
Give 4 side effects of muscarinic acetylcholine receptor antagonists (e.g. hyosine/scopolamine)?
1. Blurred vision
2. Urinary retention
3. Dry mouth
4. Centrally mediated sedation
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?
Histamine H1 receptor antagonists (e.g. cyclizine, cinnarizine)
Name two histamine H1 receptor antagonists?
What are the two locations of H1 receptors that histamine H1 receptor antagonists block?
Give a side effect of histamine H1 receptor antagonists?
What class of drugs are used for drug-induced vomiting, chemotherapy, treatment of parkinsons disease and GI disorder vomtiing?
Dopamine receptor antagonists
Name two dopamine receptor antagonists?
Domperidone and metoclopramide
What structures do dopamine receptor antagonists peripherally exert a prokinetic action on?
Oesophagus, stomach and instestine
Does domperidone cross the blood brain barrier?
What are phenothiazines used for?
Severe nausea nad vomiting
Name a NK1 receptor antagonist?
What are NK1 receptor antagonists used in combination with?
5-HT3 receptor antagonist and dexamethasone
Name a cannabindoid (CB1) receptor antagonist?
What drug is used for treating cytotoxic chemotherapy that is unresponsive to other anti-emetics?
Nabilone (cannabinoid CB1 receptor antagonists)