VOMITING(Emesis)

What is the major physiological function of vomiting

to remove non-toxic or

harmless substances

from the body after

ingestion

EMESIS

CAN IT BE BENEFICIAL

VALUABLE PHYSIOLOGICAL

RESPONSE TO INGESTION OF

TOXIC SUBSTANCES E.G.

ALCOHOL

Can you tell us some clinical problems that might occur due to nausea and vomiting

postoperative nausea and

vomiting

• Extended hospital stays,

• Increased bleeding,

• Aspiration pneumonia

• Re-opening of surgical wounds

Reflex mechanism of vomiting

• Chemoreceptor Trigger Zone (CTZ)• Vomiting centre

Three phases:

NAUSEA, RETCHING and VOMITING

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

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. 

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. 

Neuronal pathways, transmitters and

receptors involved in

nausea and vomiting

Mechano and Chemo receptors

located in

• stomach, jejunum and ileum

involved with • detection of emetic stimuli in the

gastrointestinal tract.

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

Afferent neuronal pathways from the abdomen are the

same regardless of the stimulus.

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

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.

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.

Mechanism

• Impulses from CTZ pass to area of brainstem called vomiting centre that control and integrate the visceral and somatic functions involved in vomiting.

Main neurotransmitters involved in control of vomiting

• Acetylcholine

• Histamine

• 5-HT

• Dopamine

• Enkephalins

• Substance P

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

Causes of Vomiting

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

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

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,

Cancer chemotherapeutic agents and radiation therapy

• produce free radicals enterochromaffin cells

serotonin.

• also stimulate CTZ receptors

The management of Nausea &Vomiting

• 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

Antiemetics

Class DrugAnti-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

Receptors antagonists

•Which receptors

H1 - Histamine receptors Muscarinic receptors 5 HT 3 receptors

Antiemetic DrugsH1- receptor antagonist • Cyclizine• Meclizine • Cinnarazine• Promethazin• Diphenhydramine• Dimenhydrinate • Hydroxyzine

Muscarinic antagonist • Hyoscine (Scopolamine)

D2-receptor antagonistPhenothiazine • Chlorpromazine,

prochlorperazine,Promethazine Trifluoperazine. Thiethylperazine.

Butyrophenones: • Haloperidol• Droperidol MetoclopramideDomperidone

5 HT3-receptor antagonistOndansetronGranisetronDolasetron

Cannabinoids• Nabilone• Dronabinol

Steroids • Dexamethasone• Methylprednisolone

Clinical Uses of Anti emetics

• Histamine H1 receptor antagonist

Cyclizine Motion sickness

Cinnarazine Motion sickness, vestibular disorders

Promethazine Morning sickness of pregnancy

Muscarinic antagonist

Hyoscine Motion sickness

Dopamine D2 receptor antagonist

Phenothiazines vomiting caused byProchlorperazine uremia, radiation,viral

gastroenteritis, severe morning sickness of pregnancy.

Metoclopramide uremia,

radiation, GI disorders, cytotoxic drugs.

5-HT3- receptor antagonist

Drugs Vomiting caused by

Ondansetron

Granisetron

Dolasetron

cytotoxic anticancer drugs,

post operative vomiting,

radiation induced vomiting

Cannabinoids Vomiting caused by anticancer drugs

5 HT3 Antagonists

Ondansetron, Granisetron,Dolasetron, TropisetronPrimary site of action: CTZTherapeutic Use: chemotherapy and radiation induced nausea & vomitingAdverse effects: Rare (headache,GI

upsets).

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

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

Cannabinoids Dronabinol, Nabilone• Synthetic cannabinol derivative• Mechanism of action: unknown

Adverse effects: common: • Drowsiness,dizziness, dry mouth.• Mood changes• Postural hypotension• Hallucinations

Corticosteroids

High dose Glucocorticoids

• Dexamethasone

• Methylprednisolone

• Mechanism of action: unclear

may involve inhibition of PGs