Drugs to Control or Stimulate Vomiting - The Merck Veterinary Manual

Drugs to Control or Stimulate Vomiting

The vomiting reflex is initiated by conditions that stimulate the emetic center of the medulla. (See also Vomiting: Introduction .) Emetics stimulate either peripheral receptors or directly stimulate central vomiting centers. The peripheral-acting emetics directly stimulate the pharynx, which triggers the emetic center via the ninth cranial nerve, or the visceral afferent nerves of the stomach and intestines by causing irritation, inflammation, or distention. Vomiting can be initiated centrally by intracranial stimuli (head trauma, increased intracranial pressure, or psychic stimuli) or by stimulation of the vestibular apparatus (motion sickness, vestibulitis). Toxins or drugs, such as digoxin and anticancer drugs, directly stimulate the chemoreceptor trigger zone (CTZ) because it is not protected by a complete blood-brain barrier. Acetylcholine is the primary neurotransmitter acting on the emetic center. The CTZ is stimulated by dopamine, α₂ -adrenergic drugs, serotonin, and histamine.

Emetic Drugs:

These are usually administered in emergency situations after ingestion of a toxin (Table: Emetic Drugs). They generally remove <80% of the stomach contents.

Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist).

Xylazine is an α₂ -adrenergic agonist used primarily for its sedative and analgesic action. It is a reliable emetic, particularly in cats, in which it stimulates the CTZ. Because xylazine can produce profound sedation and hypotension, animals should be closely monitored after administration. The IV route is preferred over IM administration.

Syrup of ipecac is an over-the-counter preparation that contains emetine, a toxic alkaloid that produces vomiting by acting as a stomach irritant. It usually, but not consistently, produces vomiting in 15-30 min. If repeated use fails to induce emesis, then gastric lavage is necessary to remove the emetine to prevent additional toxicosis.

Hydrogen peroxide (3%) or salt applied to the back of the pharynx stimulates vomiting via the ninth cranial nerve. Small doses (5-10 mL) of hydrogen peroxide can be administered via oral syringe until emesis occurs. It should be administered cautiously, especially in cats, because aspiration of hydrogen peroxide foam causes severe aspiration pneumonia.

Antiemetic Drugs:

Protracted vomiting is physically exhausting and can cause dehydration, acid-base and electrolyte disturbances, and aspiration pneumonia. Antiemetic drugs are used to control excessive vomiting once an etiologic diagnosis has been made, to prevent motion sickness and psychogenic vomiting, and to control emesis from radiation and chemotherapy (Table: Antiemetic Drugs). Antiemetics may act peripherally to reduce afferent input from receptors or to inhibit efferent components of the vomiting reflex response. They may also act centrally to block stimulation of the CTZ and emetic center.

The phenothiazine tranquilizers antagonize the CNS stimulatory effects of dopamine, thereby decreasing vomiting from many causes. These drugs also have antihistaminic and weak anticholinergic action. Phenothiazine tranquilizers used as antiemetics include acepromazine, chlorpromazine, and prochlorperazine. Potential side effects include hypotension due to α-adrenergic blockade, excessive sedation, extrapyramidal signs, and a lowering of the seizure threshold in epileptics. Extrapyramidal signs can be counteracted with an antihistamine (such as diphenhydramine).

The anticholinergic drugs block cholinergic afferent pathways from the GI tract and the vestibular system to the vomiting center. Alone, they are less effective than the other emetics. Atropine, scopolamine, and isopropamide cross the blood-brain barrier. They tend to have a brief duration of effect and cause excitement in cats. Peripherally acting anticholinergic drugs include glycopyrrolate, propantheline, and methscopolamine. Only isopropamide and propantheline are commonly used in small animals for vomiting related to vestibular stimulation (see also motion sickness, Motion Sickness: Introduction).

The antihistamines can block both cholinergic and histaminic nerve transmission responsible for transmission of the vestibular stimulus to the vomiting center. The histamine (H₁)-blocking drugs include diphenhydramine, dimenhydrinate, promethazine (a phenothiazine with H₁ -blocking effects), cyclizine, and meclizine. They may cause mild sedation, especially diphenhydramine, dimenhydrinate, and promethazine. Cyclizine and meclizine are potentially teratogenic at high doses.

Metoclopramide exerts its antiemetic effects via 3 mechanisms. At low doses, it inhibits dopaminergic transmission in the CNS, while at high doses, it inhibits serotonin receptors in the CTZ. Peripherally, metoclopramide increases gastric and upper duodenal emptying. Metoclopramide is a popular antiemetic for small animals. It is used to control emesis induced by chemotherapy, nausea and vomiting associated with delayed gastric emptying, reflux gastritis, and viral enteritis. There is tremendous individual variability in metoclopramide pharmacokinetics, and oral bioavailability is only ~50% due to a significant first-pass effect. At high doses or with rapid IV administration, metoclopramide causes CNS excitement by dopamine antagonism (similar to the phenothiazine tranquilizers). Extrapyramidal signs can be counteracted with an antihistamine such as diphenhydramine. Metoclopramide should not be administered if a GI obstruction or perforation is suspected.

The serotonin antagonists ondansetron and dolasetron are specific inhibitors of serotonin subtype 3 receptors in the CTZ. These receptors are located peripherally on vagal nerve terminals and centrally in the area postrema of the brain. Cytotoxic drugs and radiation damage the GI mucosa, causing release of serotonin. These are the most effective antiemetics used in people undergoing radiation and chemotherapy, and they have been used in dogs receiving chemotherapy. Ondansetron is not effective for emesis caused by motion sickness. Side effects of dolasetron include ECG changes (PR and QT prolongation, QRS widening) caused by dolasetron metabolites that block sodium channels.

Butorphanol is an effective antiemetic for dogs receiving cisplatin chemotherapy. It causes only mild sedation. It is believed to exert its antiemetic effect directly on the vomiting center.