Nausea and vomiting is one of the most common clinical symptoms. It seems simple, but it is not easy to find the cause. Nausea and vomiting is a complex physiological reflex process through the synergistic action of stomach, esophagus, oral cavity, diaphragm and abdominal muscles, so that gastric contents are excreted through esophagus and oral cavity.
I. Causes of Nausea and Vomiting
Nausea and vomiting is a special supervisory feeling, manifested as stomach discomfort and fullness, usually a prelude to vomiting, often accompanied by salivation and repeated swallowing, and in severe cases accompanied by There are headache, dizziness, sweating, pale complexion and rapid heart rate.
There are many causes of nausea and vomiting, which are clinically divided into reflex vomiting and central vomiting. Reflex vomiting is often caused by gastrointestinal diseases, hepatobiliary and pancreatic diseases, peritoneal and mesenteric diseases, kidney diseases, and glaucoma. Central vomiting is mainly caused by nervous system diseases, systemic diseases, anticancer drugs, morphine and other drugs, as well as poisoning and mental factors.
Two, Nausea and Vomiting Treatment
Because there are many diseases that cause nausea and vomiting, it should not be taken blindly until the cause is not known. The treatment principles of nausea and vomiting include etiological treatment, symptomatic treatment and correction of water and electrolyte imbalance.
1. Etiological treatment
If the cause of nausea and vomiting is known, it can be controlled by treating the underlying disease. Nausea and vomiting caused by inflammation should be actively treated with anti-infection. If a patient with gastrointestinal obstruction is identified, drug or surgical treatment should be taken. For patients with intracranial hypertension caused by various reasons, surgical treatment should be given or corresponding measures should be taken according to the condition. For mental vomiting, psychotherapy should be carried out, which is to establish the confidence of the patient to overcome the disease, and at the same time to give treatment such as sedation and regulation of autonomic dysfunction.
2. Symptomatic treatment
A variety of neurotransmitters and receptors are involved in the occurrence of nausea and vomiting. Patients with frequent nausea and vomiting should be given symptomatic treatment. So, what are the antiemetics? How to choose antiemetics for nausea and vomiting caused by different diseases?
H1 receptor blockers commonly used by antihistamines inhibit the gag reflex mainly by inhibiting the vomiting center and acting on cholinergic neurons in the vestibular nucleus and reticular structure. . H1 receptor blockers mainly include promethazine, meclizine, chlorpheniramine, astemizole and other drugs. Animal studies have shown that these drugs have teratogenic effects, and pregnant women should use them with caution.
There are many kinds of anticholinergic drugs, such as atropine, anisodamine, scopolamine, etc. Atropine and anisodamine mainly reduce the excitability of the vagus nerve, increase the tension of the cardiac sphincter, relieve gastrointestinal spasm, prevent vomiting and reflux, and are often used to prevent preoperative vomiting. And scopolamine is a post-ganglionic anticholinergic drug, which can inhibit the central nervous system, has effects on sedation, hypnosis and antiemetic, and has a good effect on nausea and vomiting caused by motion sickness. However, anticholinergic drugs also have some adverse effects, such as dry mouth, flushing, and increased heart rate.
3) Drugs to promote gastrointestinal motility
Currently commonly used drugs include metoclopramide, domperidone, cisapride, and erythromycin. Metoclopramide, a derivative of procainamide, blocks dopamine receptors, thereby reducing the urge to nausea and vomiting. At the same time, metoclopramide can promote pyloric peristalsis, dilate the pyloric canal, shorten gastric emptying time, and enhance the sensitivity of gastric smooth muscle to acetylcholine, thereby improving gastric peristalsis.
4) 5-HT antagonists
90% of 5-HT in the body is secreted by chromaffin cells in the gastrointestinal mucosa, which can activate 5-HT3 receptors in the intestinal mucosa and central CTZ, while 5-HT3 receptor antagonists By selectively blocking peripheral and central 5-HT3 receptors, it can effectively control chemotherapy-induced vomiting.
Selective 5-HT3 receptor antagonists have been synthesized and are widely used in clinical practice. Among them, the commonly used drugs for 5-HT3 receptor antagonists are ondansetron, gripristone, tropisetron and so on. 5-HT3 receptor antagonists were first used for emesis caused by chemotherapy, but are also effective for emesis after radiotherapy and surgery. When patients are ineffective against other antiemetics, 5-HT3 receptor antagonists are used. 5-HT3 receptor antagonists are widely tolerated and have few adverse reactions, usually mild to moderate headache, dizziness, constipation and diarrhea.
Phenothiazine drugs mainly play an antiemetic effect by selectively inhibiting CTZ or (and) directly reducing the excitability of the medulla oblongata emesis center. Commonly used drugs include chlorpromazine, promethazine , perphenazine, trifluoperazine and prochlorperazine. This class of drugs has a good effect on nausea and vomiting caused by certain drugs (such as opioids, anesthetics and chemotherapy drugs), and is also effective on cardiac vomiting caused by radiotherapy and gastrointestinal lesions.
Chlorpromazine is the most commonly used clinically, and its only mechanism of action is mainly to inhibit CTZ, and it can also counteract the emetic effect of apomorphine. Preoperative application of chlorpromazine can reduce postoperative nausea and vomiting vocalization rate by 50%; if the drug is used therapeutically after operation, nausea and vomiting symptoms can be controlled in about 30% of patients. Promethazine has sedative and strong antihistamine effect, can inhibit CTZ and vestibular system.
Butyrylbenzene drugs mainly produce strong anti-emetic effects by inhibiting CTZ in the central nervous system, and have a good effect on the prevention and treatment of postoperative nausea and vomiting. Commonly used drugs are haloperidol, fluoride Peridot and others. Intramuscular injection of 1 mg haloperidol, within 1 to 5 hours, 80% to 100% of postoperative nausea and vomiting can be controlled. The antiemetic effect of droperidol is better than that of haloperidol. The drug takes effect in 5 to 8 minutes after intravenous injection, and the best effect lasts for 3 to 6 hours. However, butyrylphenone drugs often have adverse reactions such as drowsiness, anxiety, delayed extrapyramidal reactions, delayed postoperative recovery, respiratory depression and hypotension.
The mechanism of action of cannabinoids is not clear, but it may be related to the frontal cortex and reflex inhibition of the medulla oblongata vomiting center related to mental activity. Commonly used drugs in this category include tetrahydrocannabinoids and peptafenone, which are mainly used for the antiemetic effect of chemotherapy drugs-induced nausea and vomiting. Oral administration of heptaphenone 30 minutes before chemoprevention is 80% effective against nausea and vomiting, and its effect is significantly better than that of phenothiazines, but these drugs have more adverse reactions, such as drowsiness, dry mouth, and blurred vision. Wait.
8) NK1 receptor antagonists
Substance P (SP) is a polypeptide containing 11 amino acids and belongs to the tachykinin (also known as neurokinin) family. The tachykinin receptors include NK-1, NK-2 and NK-3, of which substance P has the strongest affinity with NK-1. SP is emetic, and selective NK-1 receptor antagonists can inhibit its emetic.
The main drugs for NK1 receptor antagonists are aprepitant and fosaprepitant. Aprepitant is the first NK1 receptor antagonist approved for clinical use. Combined use with 5-HT3 receptor antagonists further reduces cisplatin-induced acute and delayed emesis. The Professional Committee of Cancer Rehabilitation and Palliative Care of the Chinese Anti-Cancer Association released the 2014 edition of the “Guidelines for the Prevention and Treatment of Vomiting Related to Cancer Treatment in China”, proposing the principle of prevention-based treatment, and recommending the “triple regimen” – aprepitant, 5-HT3 Antibody antagonists, combined with dexamethasone as the first-line chemotherapy and antiemetic treatment, this program is basically consistent with the US NCCN guidelines. Aprepitant is well tolerated, and common adverse reactions include anorexia, weakness, fatigue, constipation, diarrhea, nausea and vomiting, and the incidence is between 10% and 18%.
Glucocorticoids can be used to treat chemotherapy-related vomiting and to relieve nausea and vomiting caused by increased intracranial pressure. The commonly used drug is dexamethasone. However, the mechanism of action of glucocorticoids has not yet been clarified, and some studies suggest that it may have anti-inflammatory and antitoxin effects, reduce peripheral nerve damage, maintain normal gastrointestinal motility, and reduce delayed vomiting. In addition, some scholars believe that the antiemetic effect is achieved by inhibiting the production and release of 5-HT through both peripheral and central pathways.
Short-acting benzodiazepines are commonly used to relieve nausea, but their antiemetic effect is weak, and the drug of choice is lorazepam. These drugs are mainly used for sedation and anti-anxiety, so they have a good effect on nausea and vomiting related to anxiety, and can also improve the efficacy of other antiemetic drugs, and can also prevent vomiting.
1. Wang Mengjun. Research and development status and development trend of antiemetics[J]. Shanghai Pharmaceuticals, 2014, 35(17):6.
2. Yu Jieping, Shen Zhixiang, Luo Hesheng. Practical Gastroenterology (Second Edition) (Essential)[M]. Science Press, 2007.
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