Treatment of Vomiting and Gut Motility Disorders Flashcards
Vomiting =
emesis
a defence response
What is vomiting controlled by?
- Central neural regulation of vomiting is controlled by 2 separate units both in the medulla:
- The Vomiting (emetic) centre
- The Chemoreceptor Trigger Zone (CTZ)
What is the vomiting centre and where is it located?
- Collection of multiple sensory, motor and control nuclei
- Mainly in the medullary and pontine reticular formation, also extending into spinal cord
Where does the vomiting centre recieve nerve impulses from?
Receive nerve impulses from both vagal and sympathetic afferent nerve fibres
What does the vomiting centre trigger?
Responses to the incoming signals to coordinate emesis
Where is the chemorecetor trigger zone located?
CTZ is in the area postrema in the flood of the 4th ventricle
What is the CTZ sensitive to?
sensitive to chemical stimuli and is the main site action of drugs which stimulate vomiting
What other type of sickness does the CTZ mediate?
mediation of motion sickness
What is motion sickness caused by?
Motion sickness is caused by certain kinds of movement and the origin of the stimuli is primarily the vestibular apparatus:
What are the major triggers of nausea/vomiting?
- Stimulation of the sensory nerve endings in the stomach and duodenum
- Stimulation of the vagal sensory endings in the pharynx
- Drugs or endogenous emetic substances
- Disturbances of the vestibular apparatus
- Various stimuli of the sensory nerves of the heart and viscera
- A rise in intracranial pressure
- Nauseating smells, repulsive sights, emotional factors
- Endocrine factors
- Migraine
Draw a flow chart showing how vomiting is triggered
What are the main stages of vomiting?
- nausea
- retching
- vomiting
What is nausea?
- Feeling of wanting to vomit
- Associated with autonomic effects: salivation/pallor/sweating
- Often pro-dome of vomiting
What is retching?
- Strong involuntary effort to vomit
- Unproductive
Describe the process of vomiting
Expulsion of gastric contents through the mouth
What is projective vomiting suggestive of?
suggestive of gastric outlet or upper GI obstruction e.g. pyloric stenosis
Describe haematemesis and what is likely to cause this?
vomiting fresh or altered blood (“coffee-grounds”)
E.g. oesophageal varices, bleeding gastric ulcer
What is likely to cause early morning sickness?
pregnancy, alcohol dependence, metabolic disorders (uraemic)
What are the potential indications for anti-emetic drugs?
- Severe vomiting during pregnancy/hyperemesis gravidarum
- Postoperative nausea and vomiting
- Motion sickness
- Other vestibular disorders
- N/V induced cytotoxic chemotherapy
- Palliative care
- N/V associated with migraine
What is the most important clinical concern assoicated with vomiting?
clinical dehydration
What are the main types of anti-emetics?
- Antihistamines (H1)
- Antimuscarinics (M1)
- Dopamine antagonists (D2)
- 5HT3 antagonists
- Neurokini1 receptor antagonists
- Synthetic cannabinoids (CB1)
- Steroids
- Other neuroleptics
What drug (s) act on the higher cortical centres?
antihistamines (H1 receptors)
What causes vomiting that is triggered by higher cortical centres?
- pain
- repulsive sights and smells
- emotional factors
What drug(s) act on vestibular nuclei?
Hyoscine (M1 receptors)
What causing vomiting from the vestibular nuclei?
input from the labyrinth
What drugs act on the CTZ?
- Phenothlazines (D2 receptors)
- Domperidone (D2 receptors)
- Metoclopramide (D2 receptors)
- Droparldol, haloperidol (D2 receptors)
- Graniserton, ondansertron, palosetron (5HT3 receptors)
What drugs are used when vomiting is triggered by enterochromaffin cells
- Nabilone (CB1 receptors)
- Metoclopramide (D2)
- Graniserton, ondansertron, palosetron (5HT3 receptors)
- Aprepitant, fosaprepitant (NK1 receptors)
When are antihistamines used?
Useful in numerous causes of N/V; including motion sickness and vestibular disorders
Side effects of antihistamines
Side-effects profiles vary e.g. drowsiness and anti-muscarinic effects
Examples of antihistamines
- Cinnarizine; motion sickness, vestibular disorders
- Cyclizine; motion sickness
- Promethazine; severe morning sickness
Mechanism of antimuscarinics (M1 receptors)
Muscarinic receptor antagonists
Blockade of muscarinic receptor-mediated impulses from the labyrinth of visceral afferents
Examples of antimuscarinics
Hyoscine hydrobromide – useful in motion sickness
Comes as patch as well as tablets
Side effects of antimuscarinics
constipation, transient bradycardia, dry mouth
What is the mechanism of dopamine antagonists?
Act centrally as dopamine antagonists on the CTZ
Active against CTZ-triggered vomiting but not stomach-induced vomiting
Examples of dopamine antagonists
- The phenothiazines and related drugs; chlorpromazine, prochlorperazine
- Domperidone
- Metoclopramide
Give the mechanism of 5HT3 antagonists, their main use and an example
- Block 5HT3 receptor in GI tract and in the CNS
- Particular useful in managing N/V in patients receiving cytotoxics and in postoperative N/V
- Example:
- Ondansetron
What is the mechanism of neurokini 1 receptor antaongists, when they are used and give an example
- Adjunct to dexamethasone and a 5HT3 antagonist in preventing N/V associated with chemotherapy
- Example:
- Aprepitant
What is the main use of synthetic caniboids, what receptor do they act on and their common side effects
Nabilone
CB1 receptors
Used for N/V caused by chemo unresponsiveness to conventional anti-emetics
Common side effects of drowsiness/dizziness
When can steriods be used as anti-emetics and give an example
- Dexamethasone has antiemetic effects
- Can be used along, to treat vomiting associated with cancer chemotherapy, or in conjunction with other antiemetics
What should be done before using laxatives?
Try to reverse the cause; including diet/lifestyle changes
What are the main types of laxatives and their mechanisms
- Bulk-forming; ispaghula husk
- Stimulant laxatives; Senna
- Faecal softeners; docusate
- Osmotic laxatives; lactulose
- Peripheral opioid-receptor antagonists; methylnaltrexone bromide
Describe a bulk forming laxative
increases mass and volume of stool
ispaghula husk
describe a stimulant laxative
increases peristalsis
senna
describe a faecal softener
breaks up stool
docusate
describe an asmotic laxative
increases thre water content of the stool
lactulose
What is acute diarrhoea?
involves both an increase in the motility of the GI tract and a decrease in absorption of fluid and thus a loss of electrolyte
What are the approaches in treatment of acute diarrhoea?
- Maintenance of fluid and electrolyte balance e.g. oral rehydration preparation
- Antimotility drugs
- Antispasmodics (reduce smooth muscle tone) e.g. hyoscine butyl bromide (buscopan), mebeverine
- Occasionally antibacterial agent is indicated e.g. systemic bacterial infection, campylobacter, shigellosis and salmonellosis
What are the main treatments used to treat chronic diarrhoea?
- Antimotility agents; loperamide (Imodium)
- Adsorbents (NB not for acute diarrhoea); kaolin, light
- Bulk forming drugs (useful in controlling diarrhoea association with diverticular disease); ispaghula
What does bile contain?
- Bile salts
- Bilirubin
- Cholesterol
- Lecithin
- Plasma electrolytes
What hormone stimulates gall bladder emptying?
cholecystokinin (CCK)
What is the main treatments used for gall stones?
The use of lap chole and modern endoscopic techniques has limited the place of medication to treat gallstones
Ursodeoxycholic acid is still used to dissolve gallstones – mainly if mild symptoms and not amenable to other treatment
Treatment of biliary colic?
- may require an opioid, such as morphine or pethidine, given parenterally and/or diclofenac (NSAID) by suppository
- Parenteral/rectal route chosen as overcomes difficulties in absorption caused by vomiting
- Pain continuing for over 24 hours or accompanied by fever usually necessitates hospital admission (UV antibiotics may be required)
What are bile acid sequestrants and how do they act?
- Cholestyramine is an anion-exchange resin
- Forms an insoluble complex with bile acids in the intestine
- Relives pruritus associated with partial biliary obstruction and primary biliary cirrhosis
- Can also be used in some instances of diarrhoea e.g. Crohn’s disease
- Also, can be used in hypercholesterolaemia
