vomiting
DESCRIPTION
What is Emesis? What are the drugs used to treat emesis?TRANSCRIPT
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VOMITING(Emesis)
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What is the major physiological function of vomiting
to remove non-toxic or
harmless substances
from the body after
ingestion
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EMESIS
CAN IT BE BENEFICIAL
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VALUABLE PHYSIOLOGICAL
RESPONSE TO INGESTION OF
TOXIC SUBSTANCES E.G.
ALCOHOL
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Can you tell us some clinical problems that might occur due to nausea and vomiting
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postoperative nausea and
vomiting • Extended hospital stays, • Increased bleeding, • Aspiration pneumonia • Re-opening of surgical
wounds
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Reflex mechanism of vomiting
• Chemoreceptor Trigger Zone (CTZ)• Vomiting centre
Three phases:
NAUSEA, RETCHING and VOMITING
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Nausea• an unpleasant sensation that
immediately precedes vomiting.
Cold sweat, pallor, salivation. Noticeable disinterest in the surroundings, Loss of gastric tone. Reflux of intestinal contents into the stomach
Accompanying symptoms
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Retching• follows nausea
comprises labored spasmodic respiratory movements against a closed glottis with contractions of the abdominal muscles, chest wall and diaphragm without any expulsion of gastric contents. can occurwithout vomiting but normally it generates the pressure gradient thatleads to vomiting.
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Vomiting
caused by: • the powerful sustained contraction of the
abdominal and chest wall musculature, accompanied by • The descent of the diaphragm and the opening of
the gastric cardia. It results in the • rapid and forceful evacuation of stomach
contents up to and out of the mouth
Reflex activity that is not under voluntary control.
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Neuronal pathways, transmitters and
receptors involved in
nausea and vomiting
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Mechano and Chemo receptors
located in • stomach, jejunum and ileum
involved with • detection of emetic stimuli in the
gastrointestinal tract.
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Mechanoreceptors are
tension receptors that initiate emesis
in response to
distension and contraction
e.g. from bowel obstruction.
Chemo receptors respond to
a variety of toxins in the intestinal lumina
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Afferent neuronal pathways from the abdomen are the
same regardless of the stimulus.
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Receptors and neurotransmitters involved in mediating vomiting:
Structures Receptors Agonists Antagonists
Area postrema CTZ
D2 Apomorphine L-DOPA
Antidopaminergic drugs
Vestibular nuclei N. tractus solitarius
M, H1 Cholinomimetics Histamine
Scopolamine Dramamine
Vomiting center
M Cholinomimetics (e.g., physostigmine)
Scopolamine
Vagal sensory nerve endings
5-HT3 Serotonin Ondansetron GranisetronTropisetron
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Vomiting Centrefinal common pathway for efferent responses that produce emesis
• controls the act of vomiting. • not a discrete anatomical site, but represents inter-
related neuronal networks. • inputs include: vagal sensory pathways from the
gastro-intestinal tract and neuronal pathways from the labyrinths, higher centres of the cortex, intracranial pressure receptors and the chemoreceptor trigger zone.
• When activated induces: vomiting via stimulation of the salivary and respiratory centres and the pharyngeal, gastrointestinal and abdominal muscles.
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Chemoreceptor Trigger Centre (CTZ)
• in the area prostrema of the 4th ventricle of the brain
• acts as the entry point for emetic stimuli • CTZ is outside the blood-brain barrier • therefore responds to stimuli from either
the cerebral spinal fluid (CSF) or the blood.
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Mechanism
• Impulses from CTZ pass to area of brainstem called vomiting centre that control and integrate the visceral and somatic functions involved in vomiting.
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Main neurotransmitters involved in control of vomiting
• Acetylcholine• Histamine• 5-HT• Dopamine• Enkephalins • Substance P
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Class Drug
Anti-cholinergic scopolamine (L-hyoscine)
Anti-histamine cinnarizine cyclizine promethazine
Dopamine antagonists metoclopramide domperidonedroperidol (withdrawn 2001)haloperidol
Cannabinoid nabilone
Corticosteroid dexamethasone
Histamine analogue betahistine
5HT3-receptor antagonist
granisetronondansetrontropisetron
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Causes of Vomiting
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Drug/treatment - induced
Cancer chemotherapyOpiates, NicotineAntibiotics, Radiotherapy
Labyrinth disorders Motion, Meniere's disease
Endocrine causes Pregnancy
Infectious causes GastroenteritisViral labyrinthitis
Increased intracranial pressure
Haemorrhage, Meningitis
Post-operative Anaesthetics, AnalgesicsProcedural
CNS causes Anticipatory Migraine, Bulimia nervosa
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Drugs causing emesis.
a. Drugs acting on CTZ. • apomorphine • emetine (when given parenterally and only at
large doses) • L-DOPA • estrogens (morning sickness of pregnancy) • ergot alkaloids • cardiac glycosides • opiates • cancer chemotherapeutic agents
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b. Drugs acting locally on the G-I tract.
• Activate enterochromaffin cells • secrete serotonin • acts on the 5-HT3 receptors• at the nerve endings of the vagal sensory fibers. • The afferent fibers transmit excitation to the N.
tractus solitarius, • which in turn activates the VC. • These drugs are traditionally called "local
irritants". • Ipecac, zinc salts, copper sulfate,
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Cancer chemotherapeutic agents and radiation therapy
• produce free radicals enterochromaffin cells
serotonin. • also stimulate CTZ receptors
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The management of Nausea &Vomiting
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• Identification and elimination of the underlying cause if possible
• Control of the symptoms if it is not possible to eliminate the underlying cause
• Correction of electrolyte, fluid or nutritional deficiencies
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Antiemetics
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Class Drug
Anti-cholinergic scopolamine (L-hyoscine)
Anti-histamine cinnarizine cyclizine promethazine
Dopamine antagonists metoclopramide domperidonedroperidol (withdrawn 2001)haloperidol
Cannabinoid nabilone
Corticosteroid dexamethasone
Histamine analogue betahistine
5HT3-receptor antagonist
granisetronondansetrontropisetron
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Receptors antagonists
•Which receptors
H1 - Histamine receptors Muscarinic receptors 5 HT 3 receptors
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Antiemetic DrugsH1- receptor antagonist • Cyclizine• Meclizine • Cinnarazine• Promethazin• Diphenhydramine• Dimenhydrinate • Hydroxyzine
Muscarinic antagonist • Hyoscine (Scopolamine)
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D2-receptor antagonistPhenothiazine • Chlorpromazine,
prochlorperazine,Promethazine Trifluoperazine. Thiethylperazine.
Butyrophenones: • Haloperidol• Droperidol MetoclopramideDomperidone
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5 HT3-receptor antagonistOndansetronGranisetronDolasetron
Cannabinoids• Nabilone• Dronabinol
Steroids • Dexamethasone• Methylprednisolone
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Clinical Uses of Anti emetics
• Histamine H1 receptor antagonist
Cyclizine Motion sickness
Cinnarazine Motion sickness, vestibular disorders
Promethazine Morning sickness of pregnancy
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Muscarinic antagonist
Hyoscine Motion sickness
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Dopamine D2 receptor antagonist
Phenothiazines vomiting caused byProchlorperazine uremia, radiation,viral
gastroenteritis, severe morning sickness of pregnancy.
Metoclopramide uremia,radiation, GI disorders, cytotoxic drugs.
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5-HT3- receptor antagonist
Drugs Vomiting caused by
OndansetronGranisetron Dolasetron
cytotoxic anticancer drugs, post operative vomiting, radiation induced vomiting
Cannabinoids Vomiting caused by anticancer drugs
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5 HT3 Antagonists
Ondansetron, Granisetron,Dolasetron, TropisetronPrimary site of action: CTZTherapeutic Use: chemotherapy and radiation induced nausea & vomitingAdverse effects: Rare (headache,GI
upsets).
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Phenothiazines • Antipsychotics• Commonly used for: nausea and vomiting
associated with vertigo, motion sickness, and migraine.
• Act mainly as: antagonist at dopamine D-2 receptors in the CTZ
• Also block: muscarinic and histamine receptors
• Adverse effects: sedation,hypotension, extra pyramidal
symptoms
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Metoclopramide and Domperidone• D2 receptor antagonist in CTZ.• Peripheral prokinetic activity:
• Domperidone does not cross BBB.Incontrast • Metoclopramide crosses BBB Movement disorder, fatigue, spasmodictorticollis, occulogyric crises, increased prolactinrelease galacorrhea,menstrual irregularities
Increase the motility of esophagus, stomach, and intestine
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Cannabinoids Dronabinol, Nabilone• Synthetic cannabinol derivative• Mechanism of action: unknown
Adverse effects: common: • Drowsiness,dizziness, dry mouth.• Mood changes• Postural hypotension• Hallucinations
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Corticosteroids
High dose Glucocorticoids• Dexamethasone• Methylprednisolone
• Mechanism of action: unclear
may involve inhibition of PGs