Download Problem 71- Vomiting, anorexia, nausea

Core Problem 71- Vomiting, anorexia, nausea
Basic Medical Sciences
Vomiting: forceful expulsion of the contents of the stomach and upper intestinal
tract through the mouth.
It is a complex reflex coordinated by a region in the brainstem medulla oblongata
known as the ‘vomiting centre’.
Vomiting Centre:
 In the lateral reticular formation of the medulla at the level of the olivary
nuclei. Receives afferents from:
 Limbic cortex.
 CTZ (chemoreceptor trigger zone)
 Nucleus solitarius- afferents complete the arc for the gag reflex.
 Spinal cord- involved in the nausea that accompanies physical
injury.
 Vestibular system- nausea and vomiting caused by vestibular
disease and motion sickness.
 A key source of stimulation is the CTZ in the area postrema of the brain,
which is outside the blood brain barrier, and is sensitive to toxins in the
blood and can initiate vomiting.
NB: the CTZ possesses many dopamine (D2) receptors, which explains why
dopaminergic drugs used in the treatment of Parkinson’s cause nausea and
vomiting.
 Emetics can stimulate vomiting via receptors in the: stomach, duodenum,
or brain.
 Vomiting centre projects to the vagus nerve and to the spinal motor
neurones supplying the abdominal muscles.
Benefits:
 Removal of ingested toxic substances before they can be absorbed.
 Nausea that accompanies may condition you to avoid future ingestion of
foods containing such toxic substances.
Vomiting Process:
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Increased salivation, sweating, increased heart rate, pallor and nausea.
Deep breath, closure of glottis and elevation of the soft palate.
Abdominal muscles contract, increasing abdominal pressure, which is
transmitted to stomach’s contents.
Lower oesophageal sphincter relaxes and high abdo pressure forces
contents of stomach into the oesophagus.
Core Problem 71- Vomiting, anorexia, nausea
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This is known as ‘retching’ (can occur multiple times without expulsion
via mouth).
Vomiting occurs when abdominal contractions become so strong that
increased intrathoracic pressure forces contents of oesophagus through
upper oesophageal sphincter.
Causes of Nausea and Vomiting:
1. Drug-induced vomiting
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Cytotoxic drugs vary in their emetic potential, but some, e.g. cisplatin,
cause severe vomiting in most patients.
Emetic action seems to involve the CTZ.
Dopamine antagonists are often effective antiemetics.
Pharmacology
Anti-emetics:
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Transmitters involved in the pathways concerned with emesis are not
fully known.
CTZ is rich in D2 dopamine and 5HT3 receptors.
Cholinergic and histaminergic synapses are involved in transmission from
the vestibular apparatus to the vomiting centre.
Core Problem 71- Vomiting, anorexia, nausea
Examples of Dopamine antagonists:
Name of drug
Class of
drug
MOA
Use
Adverse effects
Prochlorperazine
Phenothiazi
ne
(antipsychot
ic agents)
Blocks
dopamine
receptors.
Alleviate
symptoms of
vertigo.
Antiemetic,
particularly for:
chemotherapy,
radiotherapy
and pre/post-op.
Sedative.
Neurolepticsblock dopamine
receptors in the
basal ganglia
resulting in
extrapyramidal
effects i.e.
parkinsonism,
acute dystonic
reactions,
akathisia and
tardive dyskinesia.
RARE: Neuroleptic
malignant
syndrome.
Metoclopramide
D2
antagonist.
D2
antagonist
and
prokinetic
action on gut
and
increases
absorption
of many
drugs.
Nausea and
vomiting e.g.
chemotherapy,
post-op.
Facilitate gastric
emptying in
those with
gastricparesis.
Mild adverse
effects.
Severe dystonic
reaction may
occur, mainly in
young and female.
Useful in
migraine in
combo with
paracetamol
(acetaminophen)
Domperidone
D2
antagonist.
Similar to
metoclopra
mide but
doesn’t cross
blood-brain
barrier.
Nausea and
vomiting.
Promotes
lactation as
results in
increased
Rarely causes
sedation or extrapyramidal sideeffects.
Core Problem 71- Vomiting, anorexia, nausea
prolactin
secretion due to
dopamine
inhibition.
Gastroparesis.
5HT3 antagonists examples:
Name of drug
MOA
Use
Adverse effects
Ondansetron
Serotonin
5-HT3 receptor
antagonist
Primary drugs
used to treat
chemotherapyinduced nausea
and vomiting.
Constipation, dizziness and
headache.
Reduces activity
of vagus nerve,
which
deactivates the
vomiting centre
and blocks
serotonin
receptors in the
CTZ.
Post-op and post
radiation, nausea
and vomiting.
NB: combo of
ondansetron and
dexamethasone
will prevent
cisplatininduced emesis
in most patients.
Motion Sickness
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Dopamine antagonists and 5HT3 antagonists are ineffective in reducing
the nausea and vomiting of motion sickness.
Antimuscarinic drugs or antihistamines, which act directly on the
vomiting centre, may be effective, although side-effects are common.
Symptoms and signs of this develop gradually but eventually culminate in
vomiting or retching, after which there is often a temporary lessening of
malaise.
Motion sickness is believed to be a response to conflicting sensory
information (i.e. signals from the eye and vestibular systems do not
agree).
Treatments:
Antimuscarinic- Hyoscine: one of the most effective agents for motion sickness.
Muscarinic receptor antagonist and frequently causes drowsiness, dry mouth
and blurred vision.
Core Problem 71- Vomiting, anorexia, nausea
Antihistamine- Cinnarizine- interferes with the signal transmission between
vestibular apparatus of the inner ear and the vomiting centre of the
hypothalamus. Produces fewer side-effects than hyoscine, namely: drowsiness
and blurred vision.
NB: must be taken 2 hours before provocative stimulation.
Vestibular disease
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The labyrinths generate a continuous input to the brainstem.
Any pathological process that alters the balance of this ‘tonus’ may cause
dizziness.
Major symptom is vertigo, which is a false sense of rotary movement,
associated with sympathetic overactivity, nausea and vomiting.
Acute labyrinthitis:
 Often presents abruptly with nausea and vomiting. Frequently regarded
as viral or postviral syndrome.
 Meniere’s disease- results from increased pressure in the membranous
labyrinth. Attacks of severe vertigo associated with nausea and vomiting,
deafness and tinnitus occur several times, followed by long periods of
remission.
 Between attacks, the deafness and tinnitus persist and gradually worsen.
Treatment:
1. Antihistamines: cinnarizine, cyclizine
Cyclizine:
 Piperazine derivative with histamine H1- receptor antagonist activity.
 May have direct effects on the labyrinthine apparatus and on the CTZ.
 Exerts a central anticholinergic action.
 Caution: patients with- glaucoma, urinary retention or prostatic
enlargement.
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2. Phenothiazines i.e. promethazine and prochlorperazine.
3. Betahistine:
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Drug used specifically for meniere’s.
Has a very strong affinity as an antagonist for histamine H3 receptors and
a weak affinity as an agonist for histamine H1 receptors.
Two modes of action:
Core Problem 71- Vomiting, anorexia, nausea
1. Direct stimulating effect on H1 receptors located on blood vessels in the
inner ear. Gives rise to local vasodilation and increased permeability,
which helps to reverse the problem of endolymphatic hydrops.
2. Powerful antagonist effects at H3 receptors, and increases the levels of
neurotransmitters released from the nerve endings. This explains the
potent vasodilatory effects.
Side-effects: headache, digestive-related side-effects.
NB: In pregnancy, anti-emetics should only be used for intractable vomiting
because of possible, but undefined, risk to the fetus. Limited evidence suggests that
promethazine is safe.
Behavioural Sciences
Eating disorders (anorexia nervosa and bulimia): Please see core problem
27: addictive behaviour.
Index Conditions
Many conditions cause vomiting, nausea or anorexia (or all three!). All the
conditions are covered in other core clinical problems.