20. Nausea and Vomiting Flashcards
What is the purpose of nausea and vomiting?
List some common causes of vomiting.
What physical, internal changes happen when vomiting?
Defensive responses - GI tract interacts with external env so needs to defend itself!
Chemo-radiotherapy, gastroporesis, general anaesthesia, intestinal obstruction, meds (e.g. NSAIDS, asprin), motion sickness, morning sickness, migraine, rotavirus
Powerful sustained contraction of abdominal muscles, diaphragm descent, gastric cardia opens, tachycardia, sweat, vasoconstriction, airway secretion, small intestinal retropulsion, gastric fundus relaxation. COORDINATED REFLEX.
What cranial structures coordinate vomiting?
List the sensory inputs to the vomiting centre, and the receptors involved.
Several structures in medullary reticular fomation of the hindbrain, vomiting centre = NTS and Area Postrema (AP), which project to motor nuclei including venterolateral medulla and dorsal motor nucleus of vagus (DMV)
1) Gut (e.g poisons, toxins, obstruction) -> liver -> blood circulation -> AP (poorly protected by BBB so detects circulating toxins) -> NTS/ BS motor nuclei. D2 receptors
2) Abdominal vagus nerve -> NTS (and less to to AP). 5-HT3 receptors
3) Pain sent via spinal cord to BS motor nuceli. Steroid receptors
4) Brain compression from trauma/tumour growth/abnormal motion, or psychogenic -> BS motor nuclei. H1, M1 receptors
5) Heart (ischaemia) -> vagus via 5-HT3 receptors -> NTS via NK1
* Diff receptors thus no single anti-emetic drug!*
What neurotransmitters work on the following receptors, and what categories are they divided in to?
a) M1
b) D2 and H1
c) CB1
d) 5-HT3 and NK1
Which ones are GPCR?
a) ACh - motion sickness
b) DA and histamine - old, multi-use
c) cannabinoid - other
d) serotonin and substance p (neurokinin receptors) - new/cancer
Most apart from 5-HT3 - LGIC
What are the ‘old’ anti-emetic drugs?
Give an example of a drug to treat motion sickness - what does it do?
How do the ‘old’ anti-emetic drugs work?
Muscarinic receptor antagonists (SE = urinary retention, dry mouth), dopamine D<strong>2</strong> receptor antagonists (block in AP, but SE = extrapyrimidal symptoms), histamine H1 receptor antagonists (SE = drowsiness), cannabinoid derivatives
Hyoscine - antimuscarinic (blocks ACh effects in BS and/or vestibular nuclei). Can also use amphetamine and some H1 receptor antagonists e.g. cyclizine. WILL NOT WORK ON CHEMOTHERAPY SICKNESS (and chemo anti-emetics won’t work on motion sickness)
Block AP (D2) and receptors in BS nuclei (M1, H1, CB1) (pic)
What are the ‘new’ anti-emetic drugs, and what were they developed for?
Name an anti-cancer drug with a very high emetogenic potential.
How do anti-cancer chemotherapeutic drugs (cytostatic treatment) cause nausea/vomiting?
5-HT3 receptor antagonists, NK1 receptor antagonists, corticosterone. Developed to treat severe effects of anti-cancer drugs
Cisplatin - produces acute, delayed and then ‘anticipatory’ vomiting
Liberate 5-HT from enterochromaffin cells lining upper GI tract (almost 90% of total body 5-HT is in gut- for defence etc.). Acts directly on/via 5-HT3 on vagus. Also sensitises nerve = liberation of cytokines etc. = longevity of vomiting
How do 5-HT3 receptor antagonists work?
Name a corticosteroid commonly given to cancer patients in combination with a 5-HT3 receptor antagonist.
How does the corticosteroid work?
How do NK1 receptor antagonists work?
Prevent chemotherapy-induced emesis by acting mostly at GI vagal nerve endings
Dexamethasone
Anti-innflammatory and enti-emetic/nausea, enhances anti-emetic efficacy of other anti-emetics, may increase appetite
Achieves more control when given with other anti-emetics. Blocks actions of substance P (NT used by vagus and some BS nerves)
What would you prescribe a patient for moderately severe emesis?
What would you prescribe a patient for very severe emesis?
What else are these drugs used for apart from cancer?
What might you use if nausea/vomiting was due to partial bowel obstruction?
What might you use if nausea/vomiting was due to total bowel obstruction?
5-HT3 receptor antagonist + dexamethasone
5-HT3 receptor antagonist + dexamethasone + NK1 receptor antagonist
Palliative medicine - also need to consider what’s causing nausea e.g. opiates? reflux? GI obstruction?
Stimulate GI propulsion: Metoclopramide (D2 antagonist, 5-HT4 agonist), Prucalopride (5-HT4 agonist) (drugs have 20 anti-emetic effect)
Reduce inflammation with dexamethasone, reduce build-up of fluid in lumen with NG tube/venting/Octreotide (somatostatin antagonist, may also reduce pain) NB: THESE ARE ADJUNCTS
Describe nausea?
What is ghrelin, and what are its actions?
What effect does it have on cancer patients with impaired appetite/receiving chemotherapy?
Unpleasant feeling at back of throat, awareness of vomit urge, often accompanied by cold sweat, pallor, salivation, loss of gastric tone, duodenal contractions, reflux
Ghrelin = liberated when hungry, increases appeptite, reduces vomiting, increases gastric emptying
Increased appetite and food intake, reduced cachexia and nausea
What causes gastric rhythms?
How are these affected duing nausea?
Slow waves of electrical activity migrate corpus -> pylorus at 3 cycles/minute (rhythm). Initiated by interstitial cells of Cajal in muscle
4-9 cycles/minute as opposed to 3 on electrogastrophagy, increaese in irregularity, ICC out of sync, may be a cuase of nausea = gastric dysrhythmia
