Antiemetic Drugs: What to Prescribe and When

 

HEALTH:

Emesis: Vomiting occurs due to stimulation of the emetic(vomiting) Centre situated in the medulla oblongata. Multiple pathways can elicit vomiting.

The chemoreceptor trigger zone (CTZ) located in the area postrema and the nucleus tractus solitarius (NTS) are the most important relay areas for afferent impulses arising in the g.i.t, throat and other viscera.

Nausea: Is accompanied by reduced gastric tone and peristalsis. In emetic response fundus and body of stomach, esophageal sphincter and esophageal relax, glottis closes, while duodenum and pyloric stomach contract in a retrograde manner. Rhythmic contractions of diaphragm and abdominal muscles then compress the stomach and evacuate its contents via the mouth. Conditions that inhibit gastric emptying predispose to vomiting.

All emetics are contraindicated in:

1. Corrosive (acid, alkali) poisoning: risk of perforation and further injury to esophageal mucosa.
2. CNS stimulant drug poisoning: convulsions may be precipitated.
3. Kerosene (petroleum) poisoning: chances of aspiration of the liquid (due to low viscosity) and chemical pneumonia are high.
4. Unconscious patient: may aspirate the vomitus, because laryngeal reflex is likely to be impaired.
5. Morphine or phenothiazine poisoning: emetic may fail to act.

Antiemetics

These are drugs used to prevent or suppress vomiting.

Classification:

1. Anticholinergics: Hyoscine, Dicyclomine
2. H₁ antihistaminic: Promethazine, Cinnarizine, Doxylamine
3. Neuroleptic (D₂ blocker): Chlorpromazine, Triflupromazine, Haloperidol, etc.
4. Prokinetic drugs: Metoclopramide, Domperidone.
5. 5-HT₃ antagonists: Ondansetron, Granisetron, Ramosetron
6. NK₁ receptor antagonist: Aprepitant, Fosaprepitant
7. Adjuvant antiemetics: Benzodiazepines, Nabilone.

Common Antiemetics Medicines:

Hyoscine:

(0.2-0.4 mg oral, i.m) is the most effective drug for motion sickness. However, it has a brief duration of action; produce sedation, dry mouth and other anticholinergic side effect; suitable only for short brisk journeys.

Antiemetics action is exerted probably by blocking conduction of nerve impulses across a cholinergic link in the pathway leading from the vestibular apparatus to the vomiting Centre and has poor efficacy in vomiting of other etiologies.

Dicyclomine:

(10-20 mg oral) has been used for prophylaxis of motion sickness and for morning sickness. It has been cleared of teratogenic potential.

Promethazine:

These drugs afford protection of motion sickness for 4-6 hours, but produce sedation and dryness of mouth. By their anticholinergic action they block the extrapyramidal side effects of metoclopramide while supplementing its antiemetic action. Promethazine is a phenothiazine; has weak central antidopaminergic action as well. Their combination has been used in chemotherapy induced nausea and vomiting.

Cinnarizine:

It is an antivertigo drug having antimotion sickness property. It probably acts by inhibiting influx of Ca²⁺ from endolymph into the vestibular sensory cells which mediates labyrinthine reflexes.

Motion sickness:

Antiemetics with anticholinergic – antihistaminic property are the first-choice drugs for motion sickness. Antidopaminergic and anti-HT₃ drugs are less effective. All antimotion sickness drugs act better when taken ½-1 hour before commencing journey. Once sickness has started, it is more difficult to control; higher doses/parenteral administration may be needed.

Morning sickness:

The antihistaminic are suspected to have teratogenic potential, but there is no conclusive proof. Nevertheless, it is better to avoid them for morning sickness. Most cases of morning sickness can be managed by reassurance and dietary adjustment. If an antiemetic has to be used, dicyclomine, promethazine, metoclopramide may be prescribed in low doses.

Chlorpromazine:

The oldest neuroleptic (phenothiazines, haloperidol) are potent antiemetics; act by blocking D₂ receptors in the CTZ; antagonize apomorphine induced vomiting and have additional antimuscarinic as well as H1 antihistaminic property. They have broad spectrum antiemetic action effective in:

1. Drug induced and postoperative nausea and vomiting (PONY).
2. Diseases induced vomiting: gastroenteritis, uremia, liver disease, migraine, etc.
3. Malignancy associated and cancer chemotherapy (mildly emetogenic) induced vomiting.
4. Radiation sickness vomiting (less effective).
5. Morning sickness: should not be used except in hyperemesis gravidarum.

Neuroleptics are less effective in motion sickness: the vestibular pathway does not involve dopaminergic link.

Most of these drugs produce significant degree of sedation. Acute muscle dystonia may occur after a single dose, especially in children and girls. The antiemetic dose is generally much lower than antipsychotic doses. These agents should not be administered until the cause of vomiting has been diagnosed; otherwise specific treatment of conditions like intestinal obstruction, appendicitis, etc. may be delayed due to symptom relief.

Metoclopramide:

Metoclopramide, is substituted benzamide, is chemically related to procainamide, but has no pharmacological similarity with it. Introduced 1970s as a ‘gastric hurrying’ agent, it is a commonly used antiemetic.

This is drug which promote gastrointestinal transit and speed gastric emptying by enhancing coordinated propulsive motility.

Adverse effects: Metoclopramide is generally well tolerated. Sedation, dizziness, loose stools, muscle dystonias (especially in children) are the main side effects.

Long-term use can cause parkinsoniasm, galactorhoea and gynaecomastia, but it should not be used to augment lactation. No harmful effects are known when used during pregnancy. Though the amount secreted in milk is small, but suckling infant may develop loose motions, dystonia, myoclonus.

Uses:

1. Antiemetic: Metoclopramide is an effective and popular drug for many types of vomiting-postoperative, drug induced, disease associated (especially migraine), radiation sickness, etc., but is less effective in motion sickness. Though Ondansetron is preferred, metoclopramide continues to be sed for prophylaxis and treatment of vomiting induced by emetogenic anticancer drugs (Cisplatin, etc.) A higher dose (1-2 mg/kg i.v.) is often needed, but is effective when phenothiazines and antihistamines do not work. Promethazine, diphenhydramine, diazepam or lorazepam injected i.v. along with metoclopramide supplement its antiemetic actions and reduce the attending dytonic reactions. Dexamethasone i.v. also augments the efficacy of metoclopramide.

Though no teratogenic effects have been reported, metoclopramide should be used for morning sickness only when not controlled by other measures.

2. Gastrokinetics: To accelerate gastric emptying:

a) When emergency general anaesthesia has to be given and the patients has taken food less than 4 hours                      before.

b)To relieve postvagotomy or diebetic gastroparesis associated gastric stasis.

c)To facilitate duodenal intubation. Clinical efficacy is moderate.

3. Dyspepsia and other functional g.i disorders. Metoclopramide may succeed in stopping persistent hiccups.

4. Gastroesophageal reflux disease (GERD): Metoclopramide may benefit milder cases of GERD, but is much           less effective than PPIs/H_2.

It does not aid healing of esophagitis, but may be used as adjuvant to acid suppressive therapy. Any additional benefit is uncertain.