02-02-23 - Treatment of Vomiting & Gut Motility Disorders Flashcards
Learning outcomes
- Describe the physiological control of vomiting
- Explain how drugs may modify the physiological control of vomiting and gut motility
- List the drugs which may be used to modify the emetic response and gut motility
- Relate the mechanism of action for these drugs to therapeutic usage
- List the drugs which affect bile flow
What is vomiting known as?
What is it purpose?
What 2 locations in the medulla control Central neural regulation of vomiting?
- Vomiting Is known as emesis
- Its purpose to as a defence response
- 2 locations in the medulla control Central neural regulation of vomiting:
1) The Vomiting (emetic) centre
2) The Chemoreceptor Trigger Zone, CTZ
What does the vomiting centre consist of?
Where is it located?
Where does it receive impulses from?
What does the vomiting centre respond to?
- The vomiting centre consists of a collection of multiple sensory, motor and control nuclei
- The vomiting centre is mainly in the medullary and pontile reticular formation, also extending into spinal cord
- It receives nerve impulses from both vagal and sympathetic afferent nerve fibres
- The vomiting centre responds to the incoming signals to coordinate emesis
Where is the Chemoreceptor Trigger Zone (CTZ) located?
What is the CTZ sensitive to?
What is it the main site of?
What other mechanism is CTZ also involved in?
What is motion sickness caused by?
What are the 6 steps in the pathway of motion sickness?
- The Chemoreceptor Trigger Zone (CTZ) is located in the area postrema in the floor of the 4th ventricle
- CTZ is sensitive to chemical stimuli, as this area has a very permeably BBB
- The CTZ is the main site of action of drugs which stimulate vomiting
- The CTZ is also concerned with the mediation of motion sickness.
- Motion sickness is caused by certain kinds of movement and the origin of the stimuli is primarily the vestibular apparatus
- 6 steps in the pathway of motion sickness:
1) Vestibular labyrinth
2) Vestibular nuclei (brain stem)
3) Cerebellum
4) CTZ
5) Vomiting centre
6) Vomit
Describe the 9 triggers of nausea/vomiting
- 9 Triggers of nausea/vomiting:
1) Stimulation of the sensory nerve endings in the stomach and duodenum.
2) Stimulation of the vagal sensory endings in the pharynx.
3) Drugs or endogenous emetic substances.
4) Disturbances of the vestibular apparatus.
5) Various stimuli of the sensory nerves of the heart and viscera.
6) A rise in intracranial pressure.
7) Nauseating smells, repulsive sights, emotional factors.
8) Endocrine factors
9) Migraine
Describe the flow chart of control of vomiting (in picture)
What are the 3 stages of vomiting?
- 3 stages of vomiting:
1) Nausea:
* Feeling of wanting to vomit
* Associated with autonomic effects: salivation / pallor / sweating
* Often pro-drome of vomiting
2) Retching:
* Strong involuntary effort to vomit
* Unproductive
3) Vomiting:
* Expulsion of gastric contents through the mouth
When should we prescribe anti-emetic drugs?
What should we try do prior to this?
What should drugs be selected based on?
What are 7 potential indications for anti-emetic drugs use?
- We should only prescribe anti-emetic drugs when the cause of nausea/vomiting is known
- Before prescribing drugs, we should try treat the cause where possible
- If indicated, pick drug according to the aetiology (cause) of vomiting
- 7 potential indications for anti-emetic drugs use:
1) Severe vomiting during pregnancy / hyperemesis gravidarum (mothers can become dehydrated and affect foetal outcomes
2) Postoperative nausea and vomiting
3) Motion sickness
4) Other vestibular disorders
5) N/V induced by cytotoxic chemotherapy
6) Palliative care
7) N/V associated with migraine
What are 8 different types of antiemetics?
What receptors do they each work on?
- 8 different types of antiemetics with receptors they on:
1) Antihistamines (work on H1 receptors)
* Work in higher cortical centres
* Work in a broad way with signals originating from many areas
2) Antimuscarinics (M1)
3) Dopamine antagonists (D2)
4) 5HT3 antagonists
5) Neurokinin 1 receptor antagonists
6) Synthetic cannabinoids (CB1)
7) Steroids
8) Other neuroleptics
What receptors do antihistamines work on? Where are they useful?
What are side effects of antihistamines?
What are 3 examples of antihistamines?
What are side effects of each?
- Antihistamines are H1 histamine receptor antagonists
- They are useful in numerous causes of N/V; including motion sickness + vestibular disorders (e.g dizziness/vertigo – affect vestibular system of the inner ear)
- Side-effect profiles vary e.g. drowsiness and antimuscarinic effects
- 3 examples of antihistamines with side-effects:
1) Cinnarizine - motion sickness, vestibular disorders
2) Cyclizine - motion sickness
3) Promethazine - severe morning sickness
What receptors do antimuscarinics function on? How do they work?
What is an example of an antimuscarinic?
What form do they come in?
What are 3 side-effects of antimuscarinics?
- Antimuscarinics are Muscarinic receptor (M1) antagonists
- They work by causing a blockade of muscarinic receptor-mediated impulses from the labyrinth and from visceral afferents
- Hyoscine hydrobromide is an antimuscarinic useful in motion sickness
- Comes as patch as well as tablets
- 3 side-effects of antimuscarinics:
1) Constipation
2) Transient bradycardia
3) Dry mouth
What receptors do dopamine antagonists work on?
What are/aren’t they active against?
What is an example of a dopamine antagonist?
What are 4 dopamine antagonists also classes as neuroleptics/antipsychotics?
- Dopamine antagonists work on D2 dopamine receptors on the CTZ (Chemoreceptor Trigger Zone)
- Active against CTZ-triggered vomiting but not stomach-induced vomiting
- Phenothiazines and related drugs are example of dopamine antagonists
- 4 dopamine antagonists also classes as neuroleptics/antipsychotics:
1) Chlorpromazine
2) Prochlorperazine
3) Domperidone
4) Metoclopramide
What receptors do 5HT3 antagonists work on?
What are they particular useful for?
What is an example of 5HT3 antagonists?
- 5HT3 antagonists block 5HT3 receptors in GI tract and in the CNS
- Particularly useful in managing N/V in patients receiving cytotoxics and in postoperative N/V
- Ondansetron is a 5HT3 antagonists
What anti-emetics are Neurokinin 1 receptor antagonists used alongside.
What is an example of Neurokinin 1 receptor antagonists?
- Neurokinin 1 receptor antagonists is used in combination with (adjunct to) dexamethasone (corticosteroid) and a 5HT3 antagonist in preventing N/V associated with chemotherapy
- Aprepitant is a Neurokinin 1 receptor antagonists
What is an example of a synthetic cannabinoid?
What receptors do they work on?
What are they used for?
What are common side-effects?
- Nabilone is a synthetic cannabinoid
- Synthetic cannabinoids work on CB1 receptors
- They are used for N/V caused by chemo unresponsive to conventional anti-emetics
- Common side-effects of drowsiness/dizziness
What is chronic constipation caused by?
How can we check for chronic constipation?
- Chronic constipation is caused by large stool getting stuck (impacted)
- This results in more stool forming and backing into the colon
- We can check for chronic constipation by doing a rectal examination and seeing if there is stool in the rectum
Describe the 7 types in the Bristol stool chart (in picture)
What must we do before prescribing laxatives?
What are 5 different types of laxatives?
What is an example of each type?
Describe their mechanism (in picture)
- Before prescribing laxatives we must establish patient’s norm (timing, straining every time normally?)
- We should also try to reverse the cause before prescription, including diet/lifestyle changes (e.g more fruit, vegetables, water)
- 5 different types of laxatives:
1) Bulk e.g ispaghula husk
* Not good if there is retention/colicky pain from peristalsis
2) Stimulant e.g senna
3) Softener e.g docusate
4) Osmotic e.g lactulose
5) Peripheral opioid receptor antagonist e.g methylnaltrexone bromide
- Mechanism of laxatives in picture
What are 3 conditions associated with the gallbladder?
- 3 conditions associated with the gallbladder:
1) Gallstones (cholelithiasis)
* Formed by substances in the bile salts, usually cholesterol (80% of gallstones in UK made form cholesterol
2) Acute pancreatitis
* Can be caused by gallstones moving into pancreatic duct
3) Post-hepatic jaundice
* Stones from gallbladder go into the common bile duct
