Treatment of Vomiting and Gut Motility Disorders Flashcards
Define emesis.
Vomiting, defense responsive mechanism to get rid of neurotoxins, irritant etc.
Which parts of the brain are involved in the control of vomiting?
Central neural regulation of vomiting is controlled by two separate units both in the medulla:
1) Vomiting (emetic) center
2) Chemoreceptor Trigger Zone (CTZ)
Pain, repulsive sights and smells and emotional factors from higher cortical centers are sent to the vomiting centers.
Enterochromaffin cells sense toxic chemicals or toxins in the gut. Signals are then sent through vagal afferents from the gut to the vomiting centers. Signals from vagal afferents also sent to the CTZ (main site for sensing emetic stimuli) which sends the impulse to the vomiting center.
The vomiting centers integrate incoming signals and coordinate emesis.
Signals about motion sickness from vestibular labyrinth → Vestibular nuclei (brain stem) → CTZ (main site for sensing emetic stimuli) → Vomiting centers
Which circumstances do we want to avoid vomiting in ?
Pregnancy (could be harmful to the fetus), cases of dehydration
Identify the location of vomiting center and CTZ.
1) Vomiting center: in the medullary and pontile reticular formation, also extending into spinal cord
2) Chemoreceptor trigger zone: in the area postrema in the floor of the 4th ventricle
Where does the vomiting center, and the CTZ receive impulses from ?
1) Vomiting center: Receive nerve impulses from both vagal and sympathetic afferent nerve fibres, and responds to the incoming signals to coordinate emesis
2) CTZ: sensitive to chemical stimuli and is the main site of action of drugs which stimulate vomiting. Also concerned with the mediation of motion sickness.
Are the vomiting center, and CTZ discrete areas ?
Vomiting center is not: collection of multiple sensory, motor and control nuclei
CTZ is: more discrete, in the area postrema in the floor of the 4th ventricle.
Explain how vomiting occurs in motion sickness.
Motion sickness is caused by certain kinds of movement and the origin of the stimuli is primarily the vestibular apparatus:
Vestibular labyrinth → Vestibular nuclei (brain stem) → cerebellum → CTZ → vomiting centre → vomit
Identify possible 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
Identify neurotransmitters involved in the vomiting pathway. What is their general function ?
ACh, Histamine, Dopamine, substance P, 5HT, make the pathway move forward.
Identify and describe the main 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
Identify some types of vomiting, and state the possible conditions associated with each.
- Projectile vomiting (hypertrophic pyloric stenosis in neonates, upper GI obstruction due to malignancy at older ages)
- Haematemesis (e.g. oesophageal varices, bleeding gastric ulcer)
- Early morning (e.g. pregnancy, alcohol dependence, some metabolic disorders (uraemia))
How can we determine where the bleeding occurs, in haematemesis.
Determine if vomiting fresh or altered blood (“coffee- grounds”)
Fresh implies bleeding has occurred nearer the exit (in this case, nearer the mouth)
What is the main aim of anti-emetic drugs ? Can you prescribe those when the cause is unknown ?
To stop nausea/vomiting.
Only prescribe when the cause of vomiting is known (in which case treat the cause if possible). If indicated, pick drug according to the aetiology of vomiting
Identify possible indications for anti-emetics.
- Severe vomiting during pregnancy / hyperemesis gravidarum
- Postoperative nausea and vomiting
- Motion sickness
- Other vestibular disorders
- N/V induced by cytotoxic chemotherapy
- Palliative care
- N/V associated with migraine
Identify the main types of anti-emetics. Give examples per class.
- Antihistamines (H1 receptors)
- Antimuscarinics (M1 receptors): Hyoscine
- Dopamine antagonists( D2 receptors): Phenothiazines, Metoclopramide
- 5HT3 antagonists: Graniestron, Ondansetron
- Neurokinin 1 receptor antagonists: Aprepitant, fosaprepitant
- Synthetic cannabinoids (CB1 receptors): Nabilone
- Steroids
- Other neuroleptics
Identify the site of action of:
- Antihistamines (H1 receptors)
- Antimuscarinics (M1 receptors)
- Dopamine antagonists (D2 receptors)
- Neurokinin 1 receptor antagonists
- Synthetic cannabinoids (CB1 receptors)
- 5HT3 antagonists
- Antihistamines (H1 receptors) → higher cortical centers
- Antimuscarinics (M1 receptors) → vestibular nuclei region
• Dopamine antagonists (D2 receptors) → CTZ zone or GI afferents
• Neurokinin 1 receptor antagonists →
GI afferents
• Synthetic cannabinoids (CB1 receptors) → → GI afferents
• 5HT3 antagonists → CTZ zone or GI afferents
ANTIHISTAMINES
Receptor blocked
Indications
Side effects
Examples of antihistamines and conditions used for
ANTIHISTAMINES
• Receptor blocked: H1 histamine receptor
• Indications: numerous causes of nausea and vomiting, including motion sickness and vestibular disorders
• Side effects: drowsiness and anti-muscarinic effects
• Examples:
1. Cinnarizine; motion sickness, vestibular disorders
2. Cyclizine; motion sickness
3. Promethazine; severe morning sickness
ANTIMUSCARINICS
- Receptor blocked
- Indications
- Side effects
- Examples
- Method of administration
ANTIMUSCARINICS
• Receptor blocked: Muscarinic receptors
• Indications: muscarinic-mediated impulses from the labyrinth and from visceral afferents
• Side effects: constipation, transient bradycardia, dry mouth
• Examples:
Hyoscine hydrobromide- Useful in motion sickness
• Method of administration: patch and tablets
DOPAMINE (D2 RECEPTOR) ANTAGONISTS
- Receptor blocked
- Indications
- Side effects
- Examples
DOPAMINE (D2 RECEPTOR) ANTAGONISTS
• Receptor blocked: D2 receptor
• Indications: CTZ-triggered vomiting but not stomach-induced vomiting.
• Examples:
1. The phenothiazines and related drugs
(these are also classed as neuroleptics/antipsychotics)
Chlorpromazine
Prochlorperazine
2. Domperidone
3. Metoclopramide
• Side effects: neuroleptics/antipsychotics associated with dystonic reactions and tardive dyskineasia
5HT3 ANTAGONISTS
- Receptor blocked
- Indications
- Examples
5HT3 ANTAGONISTS
- Receptor blocked: 5HT3 receptors in GI tract and in the CNS
- Indications: Particularly useful in managing N/V in patients receiving cytotoxics (e.g. chemo) and in postoperative N/V
- Examples: 1. Ondansetron
Neurokinin 1 receptor antagonists
- Receptor blocked
- Indications
- Examples
Neurokinin 1 receptor antagonists
- Receptor blocked: Neurokinin 1 receptor
- Indications: Adjunct to dexamethasone and a 5HT3 antagonist in preventing N/V associated with chemotherapy (if first line does not work)
- Examples: Aprepitant
Synthetic cannabinoids
- Receptor blocked
- Indications
- Examples
- Side effects
Synthetic cannabinoids
- Receptor blocked: CB1 receptors
- Indications: Used for N/V caused by chemo unresponsive to conventional anti-emetics
- Examples: Nabilone
- Side effects: drowsiness/dizziness
Steroids
- Example of anti-emetic steroids
- Indications of example
Steroids
- Dexamethasone has anti-emetic effects
- Can be used alone, to treat vomiting associated with cancer chemotherapy, or in conjunction with other antiemetics
Briefly describe how constipation comes about.
Hard stool, dilating the rectum, bowel movement is wider.
Chronically, softer stool is suck behind it, becomes harder, so patients get liquid on the sides .
