Reflex mechanism of vomiting• Chemoreceptor Trigger Zone (CTZ)• Vomiting centreThree phases:NAUSEA, RETCHING and VOMITING
Nausea• an unpleasant sensation thatimmediately precedes vomiting. Cold sweat, pallor, salivation. Noticeable disinterest in the surroundings, Loss of gastric tone. Reflux of intestinal contents into the stomachAccompanying symptoms
Retching• follows nauseacompriseslabored spasmodic respiratory movementsagainst a closed glottis with contractions of theabdominal muscles, chest wall and diaphragmwithout anyexpulsion of gastric contents.can occurwithout vomitingbutnormally it generates the pressure gradient thatleads to vomiting.
Vomitingcaused by:• the powerful sustained contraction of theabdominal and chest wall musculature,accompanied by• The descent of the diaphragm and the opening ofthe gastric cardia.It results in the• rapid and forceful evacuation of stomachcontents up to and out of the mouthReflex activity that is not under voluntarycontrol.
Neuronalpathways, transmittersandreceptors involved innausea and vomiting
Mechano and Chemo receptorslocated in• stomach, jejunum and ileuminvolved with• detection of emetic stimuli in thegastrointestinal tract.
Mechanoreceptors aretension receptors that initiate emesisin response todistension and contractione.g. from bowel obstruction.Chemo receptors respond toa variety of toxins in the intestinal lumina
Afferent neuronal pathwaysfrom the abdomen are thesame regardless of thestimulus.
Receptors and neurotransmitters involved in mediating vomiting:Structures Receptors Agonists AntagonistsAreapostremaCTZD2 ApomorphineL-DOPAAntidopaminergic drugsVestibularnucleiN. tractussolitariusM, H1 CholinomimeticsHistamineScopolamineDramamineVomitingcenterM Cholinomimetics(e.g.,physostigmine)ScopolamineVagalsensorynerveendings5-HT3 Serotonin OndansetronGranisetronTropisetron
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 thegastro-intestinal tract and neuronal pathways fromthe labyrinths, higher centres of thecortex, intracranial pressure receptors and thechemoreceptor trigger zone.• When activated induces: vomiting via stimulation ofthe salivary and respiratory centres and thepharyngeal, gastrointestinal and abdominal muscles.
Chemoreceptor Trigger Centre(CTZ)• in the area prostrema of the 4thventricle of the brain• acts as the entry point for emetic stimuli• CTZ is outside the blood-brain barrier• therefore responds to stimuli from eitherthe cerebral spinal fluid (CSF) or theblood.
Mechanism• Impulses from CTZ pass to areaof brainstem called vomitingcentre that control and integratethe visceral and somaticfunctions involved in vomiting.
Main neurotransmitters involved incontrol of vomiting• Acetylcholine• Histamine• 5-HT• Dopamine• Enkephalins• Substance P
Drugs causing emesis.a. Drugs acting on CTZ.• apomorphine• emetine (when given parenterally and only atlarge 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 "localirritants".• Ipecac, zinc salts, copper sulfate,
Cancer chemotherapeutic agents andradiation therapy• produce free radicalsenterochromaffin cellsserotonin.• also stimulate CTZ receptors
• Identification and elimination of theunderlying cause if possible• Control of the symptoms if it is notpossible to eliminate the underlyingcause• Correction of electrolyte, fluid ornutritional deficiencies
5 HT3 AntagonistsOndansetron, Granisetron,Dolasetron, TropisetronPrimary site of action: CTZTherapeutic Use:chemotherapy and radiation inducednausea & vomitingAdverse effects: Rare (headache,GIupsets).
Phenothiazines• Antipsychotics• Commonly used for: nausea and vomitingassociated with vertigo, motion sickness,and migraine.• Act mainly as: antagonist at dopamine D-2receptors in the CTZ• Also block: muscarinic and histaminereceptors• 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 BBBMovement disorder, fatigue, spasmodictorticollis, occulogyric crises, increased prolactinrelease galacorrhea,menstrual irregularitiesIncrease the motility ofesophagus, stomach, and intestine