Antiemetic and Antinausea Agents

• Nausea is a sensation whereas vomiting is the physiological act of regurgitation of stomach contents.

• Main area in the brain responsible for vomiting is vomiting center located in the lateral reticular formation of the medulla.

Definitions

• Nausea– Unpleasant feeling that often precedes vomiting

• Emesis (vomiting)– Forcible emptying of gastric, and occasionally,

intestinal contents

• Antiemetic agents– Used to relieve nausea and vomiting

VC and CTZ

• Vomiting center (VC)

• Chemoreceptor trigger zone (CTZ)

– Both located in the brain (Medulla)– Once stimulated, cause the vomiting reflex

Vomitting centre :Receive impulses from

– CTZ

– Vestibular apparatus

– Nucleus tractus solitarus

– Higher centers in the brain

– Peripheral structures including GIT

Phases of vomiting

• Has two phases :

– Retching phase: Upper Eso. Sphincter closed and IAP

– Expulsive phase : Upper esophageal sphincter relaxes resulting in the expulsion of gastric contents.

What causes vomitting?

• Drugs– Apomorphine and bromocriptine acts on the D2 receptor in the CTZ

– Morphine in high dose, acts in CTZ

– Syrup of ipecac: irritates gut, activation of the 5HT3 receptors(release of serotonin)

– Cisplatin: release of serotonin in the gut- acts on the 5HT3 receptors.

• Pregnancy, motion sickness, psychological

• Vomiting is believed to be controlled by two distinct brain centres—the vomiting centre and the chemoreceptor trigger zone—both located in the medulla oblongata.

• The vomiting centre initiates and controls the act of emesis, which involves a series of contractions of the smooth muscles lining the digestive tract.

Difference between vomiting and regurgitation ??

Classification (antiemetics)

1. Anticholinergics : Scopolamine and Hyoscine

2. Neuroleptic agents (D2 blocker) :-Chlorpromazine, Prochlorperazine, Haloperidol

3. H1 antihistaminics : Diphenhydramine, Meclizine , Promethazine, Cinnarizine, Cyclizine, Doxylamine

4. Prokinetic agents :-Metoclopramide , Domperidone, Cisapride.

5. Serotonin blockers (5 – HT3 antagonists) :- Ondansetron Dolasetron , Granisetron ,

Mechanism of Action

• Antihistamine agents (H1 receptor blockers)

– Inhibit ACh by binding to H1 receptors

– Prevent cholinergic stimulation in vestibular and reticular areas, thus preventing N&V

– Also used for nonproductive cough, allergy symptoms, sedation

H1 Antihistaminics

• H1 antagonists

• Also has anti muscarinic effect

• Very effective in preventing motion sickness(vestibular afferent input in vomiting centre which has h1 and muscarinic receptors)

• Promethazine :commonly used

• Cyclizine:motion sickness

• Meclizine: motion sickness , vestibular disorders (menieres disease)

• Useful if given before onset of nausea and vomitting

• Antiemetic effect occurs in about 4hrs after ingestion; effects last for 24hrs

• Teratogenic so not used in morning sickness

• Sedative so not to be used for drivers.

Mechanism of Action and Indications

• Anticholinergic agents (ACh blockers)– Bind to and block acetylcholine (ACh) receptors in the

inner ear labyrinth

– Block transmission of nauseating stimuli to CTZ

– Scopolamine and Hyoscine

– Also used for motion sickness

• Antiemetic action peaks in 1-2 hours after ingestion

• Hyoscine is used as transdermal patch behind ear.

• A/E: dry mouth, blurring of vision, retention of urine, sedation.

Mechanism of Action

• Neuroleptic agents (D2 blocker)

– Block dopamine receptors on the CTZ

– Chlorpromazine, Prochlorperazine, Haloperidol

– Also used for psychotic disorders, Antiemetic dose generally much lower than antipsychotic doses.

• Adverse effects: gynaecomastia, galactorrohea, sedation.

• Use:

• Drug induced and post anaesthetic nausea and vomiting

• Disease induced: gastroenteritis, migraine, uremia

Mechanism of Action

• Prokinetic agents– Block dopamine in the CTZ– Cause CTZ to be desensitized to impulses it

receives from the GI tract– Also stimulate peristalsis in GI tract,

enhancing emptying of stomach contents– Metoclopramide , Domperidone, Cisapride,

Mosapride– Also used for GERD, delayed gastric

emptying

Domperidone

• D2 antagonist in CTZ

• Also prokinetic agent (agent that increases GI motility)

• (Dopamine is inhibitory neurotransmitter in GITdelays gastric emptying when food is present in stomachgastric dilationLES ralaxationnausea and vomiting)

• Domperidone by blocking dopamine receptor enhance gastric emptying and increases the tone of LES.

Mechanism of Action

• Serotonin blockers (5 – HT3 antagonists)– Block serotonin receptors in the GI tract, CTZ,

and VC– Dolasetron (Anzemet), granisetron (Kytril),

ondansetron (Zofran)– Used for N&V for patients receiving

chemotherapy and postoperative nausea and vomiting

• Uses:

• Postoperative vomiting• Drug induced (morphine, pethidine)• Disease associated (migraine)• Before chemotherapy• Should not be used in morning sickness, except when

not controlled by other measures• To acclerate gastric emptying before induction of

anaesthesia for emmergency surgery• In GERD

• Rapidly absorbed orally, enters brain, crosses placenta, secreted in milk.

• A/E: sedation, dizziness, diarrhoeas, Long term use results in parkinsonism, galactorrhoes, gynaecomastia.

Mechanism of Action

• Serotonin blockers (5 – HT3 antagonists)

– Block serotonin receptors in the GI tract, CTZ, and VC

– Dolasetron, granisetron, ondansetron

– Used for N&V for patients receiving chemotherapy and postoperative nausea and vomiting

• Excellent antiemetics but costly

• Mainly used is Ondansetron

• Headache and GI upset can occur

Miscellaneous antiemetics

• Benzodiazepines: lorazepam, alprazolam

– Antiemetic effect is low, beneficial effect is due to their sedative, anxiolytic and amnesic properties

– Used as an adjuvant– Used in combination with metoclopramide and ondansetron.

• Corticosteroids: dexamethasone and methylprednisolone

– Antiemetic mechanism is unknown– Highly effective in combination with ondansetron and metoclopramide for

highly emetogenic regimens.

Therapy of vomiting

• Motion sickness: hyosine, antihistamines (promethazine, cyclizine)

• Morning sickness: frequent meals and fluids: avoid drugs; if severely nauseated promethazine, cyclizine or metoclopramide

• Chemotherapy induced: dexamethasone+ ondansetron; metoclopramide before chemotherapy

• Gastric induced: metoclopramide, domperidone

Nursing Implications

• Assess complete nausea and vomiting history, including precipitating factors

• Many of these agents cause severe drowsiness; warn patients about driving or performing any hazardous tasks

• Taking antiemetics with alcohol may cause severe CNS depression

• For chemotherapy, antiemetics are often given ½ to 3 hours before a chemotherapy agent