Vomiting and Antiemetics

7/31/2019 Vomiting and Antiemetics

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Nausea and Vomiting

are biologicaldefence mechanisms.


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The major physiological function ofemesis (vomiting) is to remove

toxic or harmful substances fromthe body after ingestion


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However, emesis is multifactorial inorigin and can be caused by a rangeof stimuli, including medicalinterventions, some of whichapparently have little to do withingesting poisonous substances.


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Stimuli causing Nausea andVomiting

Poison ingestion

Gastroenteritis

Motion

Surgery

Pregnancy

various drugs

Radiation

Disgusting sights, smells or
http://www.nauseaandvomiting.co.uk/NAVRES001-7-motion.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-3-PONV.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-6-pregnancy.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-4-opioid.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-5-chemo-radio.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-5-chemo-radio.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-4-opioid.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-6-pregnancy.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-3-PONV.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-7-motion.htm


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Classification of causes ofnausea and vomiting

Drug/treatment - induced

Labyrinth disorders

Endocrine causes

Cancer chemotherapyOpiatesNicotineAntibioticsRadiotherapy

MotionMeniere's disease

Pregnancy(25-90%)


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Classification of causes of nausea andvomitingcont.

Increased intracranial pressure

Post-operative

CNS causes

HaemorrhageMeningitis

AnaestheticsAnalgesics

ProceduralAnticipatory Pain, Fear, Anxiety

MigraineBulimia nervosa


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Problems of N & V

Distressing to patients

Clinically problematic

PONV - extended hospital stays

increased bleeding

aspiration pneumonia

re-opening of surgical wounds as a resultof the involuntary muscular contractionsassociated with vomiting.

The fear ofchemotherapy-inducednausea and vomiting can result in
http://www.nauseaandvomiting.co.uk/NAVRES001-3-PONV.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-5-chemo-radio.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-5-chemo-radio.htmhttp://www.nauseaandvomiting.co.uk/NAVRES001-3-PONV.htm


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Nausea and vomiting also imposes aneconomic burden on the healthcaresystem as a result of the time spentcleaning up, potential delays inrecovery and discharge, andincreased medical care.


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Anatomy in N & V


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Vomiting Centre

Anatomically ill defined area locatedin the medulla oblongata

Receives afferents fromCerebral cortex

Viscera

CTZ


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Chemoreceptor TriggerZone(CTZ)

Situated in the medulla, areaprostrema of the 4th ventricle of thebrain

acts as the entry point for emeticstimuli and humeral substances.

is outside the blood-brain barrierandtherefore responds to stimuli fromeither the cerebral spinal fluid (CSF)or the blood

Afferents Vestibular via cerebellum


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The vomiting reflex

The process of emesis can beclassified into three phases,

nausearetching

vomiting


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Nausea

Nausea is described as anunpleasant sensation thatimmediately proceeds vomiting.

A cold sweat, pallor, salivation, anoticeable disinterest in thesurroundings, loss of gastric tone,

duodenal contractions and the refluxof intestinal contents into thestomach often accompany nausea.


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Retching

Retching follows nausea, andcomprises laboured spasmodicrespiratory movements against aclosed glottis with contractions of theabdominal muscles, chest wall anddiaphragm without any expulsion of

gastric contents.Retching can occur without vomiting

but normally it generates thepressure gradient that leads tovomitin .


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Vomiting

Vomiting is caused by thepowerfulsustained contraction of theabdominal and chest wall

musculature, which is accompaniedby the descent of the diaphragm andthe opening of the gastric cardia.

This is a reflex activity that is notunder voluntary control.

It results in the rapid and forceful

evacuation of stomach contents up to


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Neuronal Pathway

Mechano- and chemoreceptorslocated in the stomach, jejunum andileum

Afferents

vagal sensory pathways from the gastro-intestinal tract

neuronal pathways from the labyrinths

higher centres of the cortex

intracranial pressure receptors


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Neurotransmitters in N & V

Histamine

Acetylcholine

Dopamine

Noradrenaline

Adrenaline

5-Hydroxytryptamine (5HT)

Substance P


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Receptors in the vomitingreflex

Nausea and vomiting are mediatedby three different pathways:

By visceral stimulation (dopamineand serotonin)

By CNS vestibular stimulation(histamine, acetylcholine M1)

By activation of the chemoreceptortrigger zone in the floor of the 4thventricle (dopamine, serotonin, NK1,

U).


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Receptors

CTZ DA, 5HT3, NK1, U

VC 5HT3

Gastric Dopamine, 5HT3

Vagus nerve 5HT3

Vestibular M1, H1, Ach


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Th t f


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The management ofnausea and vomiting

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

Antiemetics


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Click to edit Master subtitle style

antiemetics


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Antiemetics should be prescribedonly when the cause of vomiting isknown

Else they may delay diagnosis,particularly in children

Antiemetics are unnecessary and

sometimes harmful when the cause


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In support of their role in emesis, ithas been shown that antagonists ofreceptors for each of the transmitters

have anti-emetic effects


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Classess of Antiemetics

Anticholinergics Hyoscine,Scopolamine

Antihistamines Promethazine,Cyclizine

Dopamine Antagonists Droperidol,Metoclopromide, phenothiazines,haloperidol

5 HT3 receptor antagonists Ondansetron

e e cs


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e e cs


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It should be appreciated that manydrugs have multiple mechanismsof action


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AnticholinergicsAtropine, Hyoscine

Inhibit acetylcholine at the muscarinicreceptor.

Limits vestibular stimulation but aswith antihistamines, little effect onvisceral stimulation

Prominent anti-cholinergic side-effects - drowsiness, dry mouth,blurred vision, difficulties withmicturition

A tihi t i
http://www.patient.co.uk/DisplayConcepts.asp?WordId=ANTICHOLINERGIC&MaxResults=50http://www.patient.co.uk/DisplayConcepts.asp?WordId=ANTICHOLINERGIC&MaxResults=50


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Antihistaminescinnarizine, cyclizine,

promethazineInhibit H1 receptor and limit

stimulation by the vestibular pathway.NB. Little effect on afferent visceral

stimulation

Drowsiness and anticholinergic side-effects (dry mouth, urinary retention,

blurred vision, exacerbation ofnarrow-angle glaucoma)

Dopamine Antagonists
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Dopamine Antagonistsmetoclopramide, domperidone, haloperidol,

droperidol (withdrawn 2001)

Dopamine (D2) antagonists. Centralaction in the chemoreceptor triggerzone. Broad efficacy, limited by side-

effects.

Sedation (worse withchlorpromazine), hypotension,

extrapyramidal symptoms includingtardivedyskinesia and oculogyriccrisis, neurolepticmalignant syndrome, menstrualdisturbances, naecomastia,
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Metoclopromide

acts directly on the GI tract,increasing gastric emptying and gutmotility - Prokinetic

Superior to phenothiazines for emesisassociated with gastroduodenal,hepatic and biliary disease

-


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-

dolasetron,granisetron,ondansetron,tropis

etron,Inhibit the 5HT3 receptors in thesmall bowel, vagus nerve,chemoreceptor trigger zone i.e.

Provide a diffuse blockade and can beconsidered broad-spectrum anti-emetics

Good SE profileHeadache, diarrhoea and fatigue

QT widening.Rarely hypersensitivity

reactions

Corticosteroids


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CorticosteroidsDexamethazone,

MethylprednisoloneUnknown receptor within

Gastrointestinal tract.

Weight gain, fluid retention,immunosuppression, skin changes,Cushings syndrome and adrenalsuppression, mental disturbance,

glaucoma and cataract, osteoporosis,steroid psychosis, hyperglycaemia,peptic ulceration


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Cannabinoids

Nabilone

Synthetic cannabinoid.

Unknown receptor within CNS

Used in cytotoxic chemotherapy

Drowsiness and disorientation,

vertigo, ataxia

euro n n recep or an agon s


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euro n n recep or an agon sAprepitant, fosaprepitant,

Vofopitan

Used for acute and delayed nausea

and vomiting with cisplatin basedcytotoxic chemotherapy


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Drug treatment of N & V

Different clinical profiles.

Eg: 5-HT3 antagonists are effective

againstchemotherapy- and radiation- induced nbut do not inhibit nausea andvomiting resulting from

opiate administration or motion.Antihistamines provide effective

control ofPONV, emesis resulting

from opioids or motion but are less
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Receptors

CTZ D2, 5HT3, NK1, Mu

VC M3, H1, Mu

Gastric Dopamine, 5HT3Vagus nerve 5HT3

Vestibular M1, H1, Ach


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treatment of different typesof nausea and vomiting

A multi-drugapproach


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PONV


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High Risk Groups

Previous history of PONV/Motionsickness

High risk surgeryGynaecological

Upper abdominal

Middle earSquint surgery

Females (2-4 X than males)

Obese patients


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Opioids increase PONV by

Mu receptor action

Reduced gastric emptying

Sensitizing the vestibular systemIncreasing 5HT release

Increase ADH which causes PONV

Risk Factor Risk of PONV Prophylaxix Treatment


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Risk Factor Risk of PONV Prophylaxix Treatment

No risk 10% - Ondansetron1-4mg

1 21% - Ondansetron1-4mg

2 39% Domperidone Ondansetron1-4mg

3 61% DomperidoneorDexamethazo

ne+/-

Metoclopramide

Ondansetron1-4mg

4 79% Domperidone+Dexamethaz

one

Any otherantiemetic


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Other ways of reducing PONV

Hydrate the patient well duringsurgery and anaesthesia

Avoid N2O use air insteadUse Propofol

Avoid opioids if possible

use regional anaesthesia with LA

Use NSAIDS, other analgesics in place ofopioids if possible

Avoid ketamine if possible


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Accupressure on the P6 accupunturepoint on the wrist


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Choosing an antiemetic inother clinical situations


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Migraine

Prokinetic anti-emetics are first-line

Dopamine is thought to be a primarymediator in migraine so that theymay have a role in treating theheadache also.

lli i


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Palliative care

Drug-related (Opioids) -haloperidol or metoclopramide for thefirst 4-5 days

Associated with gastritis, gastricstasis, functional bowelobstruction

Metoclopramide and domperidone areuseful prokinetics

Do not give anti-muscarinic drugs in

combination with metoclopramide as the


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Palliative Care

Mechanical bowel obstruction

If surgery is an option, refer for asurgical opinion.

Symptomatic treatment:

dexamethasone (antiemetic and minimisesobstruction)

cyclizine/haloperidol or levomepromazine(antiemetics which may not abolishvomiting completely but aim to eliminatenausea)

Where colic is a problem, stop prokinetics

Raised intracranial


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Raised intracranialpressure

Dexamethasone, cyclizine andlevomepromazine are the drugs mostfrequently used in this context.

A i t f d i


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Anxiety, fear and pain

Benzodiazepines (such as diazepamand midazolam), cyclizine andlevomepromazine may help in this

situation.

Ch i l


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Chemical causes

Examples include hypercalcaemiaand renal failure.

Haloperidol is used for most chemicalcauses of vomiting.

Alternatives include metoclopramide,cyclizine and levomepromazine.

V iti i


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Vomiting in pregnancy

short-term treatment with an anti-histamine such as promethazinewould then be required.

Second-line drugs areprochlorperazine andmetoclopramide.

little information on the safety of5HT3 antagonists in pregnancy.

If vomiting fails to settle within 24-48

hours, refer to secondary care as the

M ti i k


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Motion sickness

Hyoscineis effective but patcheswhich provide prolonged activity needto be applied several hours prior to

setting-off.

Cyclizine or cinnarizine are lesssedating compared to promethazine

5HT3 antagonists are not effective formotion sickness.

Oth tib l di d


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Other vestibular disorders

Betahistine is licensed for thetreatment of the vertigo associatedwith Meniere's disease.

A diuretic alone may also providesome benefit.

Antihistamine and phenothiazine

antiemetics are suitable for theprophylaxis and treatment of thenausea associated with vestibular

disorders.

Treatment of Unknown


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Treatment of Unknowncauses of N&V

Sometimes despite best efforts,diagnosis of the cause of nausea andvomiting in end-stage cancer may be

possible.

Treat with a broad-spectrumantiemetic - cyclizine,

levomepromazine or metoclopramideDo not forget non-drug measures

such as avoiding food smells and

unpleasant odours, diversion and


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Good Practices

Always review antiemetic treatmentregularly.

Add in or switch to a second-linetherapy if nausea, retching andvomiting persists 24-48 hours afterstarting a first-line antiemetic.

Review and reconsider the diagnosisif symptoms persist with the second-line therapy.

Consider seeking specialist help if

S


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Summary

Nausea and vomiting is distressingfor patients, can cause significantclinical problems and imposes an

economic burden.

Rapid and effective management ofnausea and vomiting is important,

notably in cancer therapy and post-operatively.

There are multiple causes of nausea

and vomiting involving a number of


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Any Questions?


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Thank you!


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References

British National Formulary BritishMedical Association and RoyalPharmaceutical Society of Great

Britain. London.

MedicineNet.com
http://www.bnf.org.uk/bnf/http://www.bnf.org.uk/bnf/

Documents

Vomiting and Antiemetics