Nausea is a desire to vomit. It may or may not culminate in vomiting. Emesis or vomiting is a protective mechanism. It serves to eliminate harmful substances from the stomach and duodenum. Emesis is a coordinated act of medullary vomiting centre (VC) and the chemoreceptor trigger zone (CTZ), situated fri the area postrema in the floor of the fourth ventricle.
The major afferent inputs to VC are routed through CTZ which has dopaminergic (D2), histaminergic (H1), muscarinic (M1), opioid (.i) and serotonergic (5HT3) receptors. The vestibular apparatus (rich in muscarinic M1 and histaminic H1 receptors) generates impulses during motion sickness which reach VC mainly through cerebellum and also through CTZ (though D, receptor antagonists do not control motion sickness).
Irritation of gastrointestinal mucosa by irritants, chemotherapeutic agents, radiation therapy, endogenous toxins and poisons leads to activation of 5-HT3 receptors of vagal and splanchnic afferents of gut by releasing mucosal serotonin from enterochromaffin like cells. This then sends vagal afferent inputs to nucleus tractus solitarius (NTS) for onward transmission to VC either directly or through CTZ. Vomiting center contains mainly muscarinic M1, histamine H1 and serotonin 5- HT3 receptors.
Nausea and vomiting may occur even to a healthy person due to indigestion, unpleasant smell, unpalatable food, drugs and chemicals, motion sickness and pregnancy. Various diseases such as food poisoning, acute abdominal emergencies (appendicitis, obstruction of intestine), diseases of the gallbladder, liver, peritoneum, acute infective illnesses (hepatitis, cholera, meningitis, and malaria), heart diseases (myocardial infarction), etc. may cause nausea and vomiting. These various unpleasant sensory stimuli can cause nausea and vomiting by stimulation of VC via higher centers.
Emetics are the drugs which cause vomiting. Nowadays, they are not indicated in the treatment of poisoning. Apomorphine is a DA receptor agonist. It stimulates CTZ and is used as an experimental emetic agent. A large number of drugs (morphine, cytotoxic agents, digitalis glycosides, bromocriptine, NSAIDs, theophylline, etc.) are known to stimulate CTZ and induce nausea and vomiting as side effects.
They are employed for symptomatic relief of nausea and vomiting. The important antiemetics are:
1. Phenothiazines (prodilorperazine, triflupromazine, promethazine, chiorpromazine): These drugs act by blocking D2 receptors in CTZ. These agents are very effective in preventing vomiting due to almost any cause including radiotherapy and cytotoxic agents. They produce extra- pyramidal symptoms, drowsiness, and hepatotoxicity as adverse effects.
2. Metoclopramide and dompeddone: These drugs block D2 receptors in CTZ. They also act peripherally (prokinetic action) by raising the tone of cardiac sphincter, relaxing pyloric sphincter and increasing peristalsis of proximal ileum. They are useful to treat vomiting due to wide range of causes. They are of specific benefit in vomiting during anaesthesia and after surgery. Metoclopramide induces extra- pyramidal symptoms on prolonged use, drowsiness, infantile convulsions in large doses and hyperprolactinaemia. Domperid one has lesser extrapyramidal side effects and hyperprolactinaernia. Hence it is preferred over metoclopramide.
3. Cisapride: Although it is structurally related to metoclopramide, it is devoid of DA receptor blocking action. It increases gastrointestinal cholinergic activity and may produce abdominal cramps and diarrhoea. It has prokinetic effect like domperidone.
4. Antihistaminics: Dimenhydrinate, promethazine, cyclizine, meclizine, cinnarizine are H1 receptor antagonists. They may act as antiemetic agents by virtue of significant anticholinergic activity. They are used in motion sickness and labyrinthine disorders. Drowsiness, dry mouth, blurred vision may occur as side effects.
5. 5HT3 receptor antagonists (ondansetron, granisetron, zacopride): They act by blocking the 5-HT heteroreceptors modulating DA synthesis and release. They are used to control emesis due to radiotherapy and cytotoxic agents. They also have anti anxiety effect. Flushing, headache, and constipation may occur as side effects. Most commonly used drug is granisetron (10 jig/kg i.v. 30 mm prior to chemotherapy or 2mg orally 1 hour before chemotherapy). This is the one which is also used by dentist during chemotherapy- or radiation-induced nausea and vomiting in patients suffering from different oral cancers. These are also preferred by them to control postoperative nausea and vomiting.
6. Other drugs: Dexamethasone (inhibits PGE2 induced nausea and vomiting by decreasing PGE2 synthesis by inhibiting phospholipase A2) + metoclopramide (D2 receptor blocking effects) + lorazepam (for enhancing the inhibitory effect of GABA on CTZ) are used with granisetron to treat refectory emesis due to cytotoxic agents by doctors including dentists.
Treatment of vomiting associated with pregnancy: Usually no therapy is required during morning sickness. However, in severe cases promethazine is used. In hyperemesis, gravidarum pyridoxine supplement along with phenothiazines may be required.
Certain drugs promote the expulsion of gases from the gastrointestinal tract. They are called carminatives. Common carminatives are:
i. Sodium bicarbonate (Dose: 0.6—1.5 g); It reacts with gastric hydrochloride and carbon dioxide is produced. Carbon dioxide distends the stomach, relaxes lower oesophageal sphincter and causes eructation.
ii. Others (oil of peppermint: 0.06—0.1 ml; Tr. cardamom Co: 1—2 ml; oil of dil: 0.06—0.2 ml; Tr. ginger: 0.6—1 ml) are condiments and spices. They contain volatile oil which relaxes the lower oesophageal sphincter and increases gastrointestinal motility due to their mild irritant action and flavour.
They give a feeling of warmth and comfort in the epigastrium. Carminatives are used to treat flatulent dyspepsia and to prevent regurgitation of milk in infants.
Bitters are used before meals in dyspepsia. Due to their bitter taste, they reflexly promote gastric secretion and improve appetite. Commonly used bitters are Tr. gentian (2—3 ml); picrorrhiza (1—4 ml liquid extract of its powdered root); chirata (2-4 ml of infusion in 25% alcohol); ethyl alcohol (20—30 ml of 7—12%); Tr. aurantii (2—4 ml). However, their efficacy is unreliable.
A number of proteolytic, amylolytic and lipolytic enzymes are believed to promote digestion of food. However, they are only effective when their production in gastrointestinal tract is deficient. Their routine use in tonics and appetite improving mixtures is irrational. Commonly used digestants are hydrochloric acid, pepsin, papain, pancreatin, diastase and taka-diastase.
[Source: Principles of Pharmacology for Dental Students]