Vomiting center

The emetic (a drug that induces vomiting) ipecac causes vomiting because of its local irritating effect on the stomach and by stimulation of the vomiting center in the medulla... 

Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,10 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.10 Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines. 

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract. Examples of such receptors include cholinergic and histaminic, dopaminergic, opiate, serotonin, neurokinin (NK), and benzodiazepine receptors. Theoretically, chemotherapeutic agents, their metabolites, or other emetic compounds trigger the process of emesis through stimulation of one or more of these receptors. 

Dimenhydrinate Dimenhydrinate (16.1.2) is a complex componnd of iV, iV-dimethyl (2-diphenyhnethoxy)ethylamine—diphenhydramine with 8-chlorotheophylline. While blocking the Hj receptor, dimenhydrinate simultaneonsly acts on the vomiting center [4,5]. 

Meclizine actively affects the vomiting center and is used for vomiting and diarrhea. Synonyms of this drug are antivert, bonine, lamin, roclizin, and vertol. 

Pharmacology The mechanism of action of scopolamine in the CNS is not definitely known but may include anticholinergic effects. The ability of scopolamine to prevent motion-induced nausea is believed to be associated with inhibition of vestibular input to the CNS, which results in inhibition of the vomiting reflex. In addition, scopolamine may have a direct action on the vomiting center within the reticular formation of the brain stem. 

Pharmacokinetics Mechanism is obscure, but may be mediated through the chemoreceptor trigger zone direct impulses to vomiting center are not inhibited. 

Locally-acting are all agents that decrease stimulation of receptors in the GI tract. A viscous formulation of local anesthetics such as lidocaine increases the threshold of receptor-activity to vomiting. Adsorbents and mucosa protective agents like kaolin and pectin, activated charcoal, bismuth subsalicylate, attapulgite and cholestyramine have similar effects. Cola Syrup and phosphorylated carbohydrate can decrease GI muscle spasm with consequently less input into the vomiting center. 

Since Parkinson s disease arises from a deficiency of DA in the brain, the logical treatment is to replace the DA. Unfortunately, dopamine replacement therapy cannot be done with DA because it does not cross the blood-brain barrier. However, high doses (3-8 g/day, orally) of L(-)-DOPA (levodopa), a prodrug of DA, have a remarkable effect on the akinesia and rigidity. The side effects of such enormous doses are numerous and unpleasant, consisting initially of nausea and vomiting and later of uncontrolled movements (limb dyskinesias). The simultaneous administration of carbidopa (4.75) or benserazide (4.76)—peripheral DOPA decarboxylase inhibitors—allows the administration of smaller doses, and also prevents the metabolic formation of peripheral DA, which can act as an emetic at the vomiting center in the brainstem where the blood-brain barrier is not very effective and can be penetrated by peripheral DA. 

HT3 receptors in the gastrointestinal tract and in the vomiting center of the medulla participate in the vomiting reflex (see Chapter 62). They are particularly important in vomiting caused by chemical triggers such as cancer chemotherapy drugs. 5-HTip and 5-HT4 receptors also play important roles in enteric nervous system function. 

There are four important sources of afferent input to the vomiting center ... 

Nausea and vomiting may occur when the stomach is overly irritated, stimulated, or distended (from overeating). In addition, nausea and vomiting may occur when the chemoreceptor trigger zone for emesis or the vomiting center, or both, are directly stimulated. 

The vomiting center, which is located in the lateral reticular formation in the midst of a group of cells governing such activities as salivation and respiration... 

The vomiting center is activated by impulses that originate from the gastrointestinal tract and other peripheral structures. In addition, there are unidentified tracts that extend from the cerebral cortex to the vomiting center, such that emotional trauma and unpleasant olfactory and visual stimuli may cause nausea and vomiting. 

The brainstem vomiting center is located in the lateral medullary reticular formation and coordinates the complex act of vomiting through interactions with cranial nerves VIII and X and neural networks in the nucleus tractus solitarius that control respiratory, salivatory, and vasomotor centers. High concentrations of muscarinic, histamine Hi, and serotonin 5-HT3 receptors have been identified in the vomiting center. 

Selective 5-HT3 receptor antagonists have potent antiemetic properties that are mediated mainly through peripheral 5-HT3 receptor blockade on intestinal vagal afferents. In addition, central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone probably plays an important role. The antiemetic action of these agents is restricted to emesis attributable to vagal stimulation other emetic stimuli such as motion sickness are poorly controlled. 

Two brain stem sites have key roles in the vomiting reflex pathway. The chemoreceptor trigger zone, located in the area postrema (a circumventricular structure at the caudal end of the fourth ventricle) is outside the blood-brain barrier. Thus it can respond directly to chemical stimuli in the blood or cerebrospinal fluid. The second important site, the vomiting center, located in the lateral reticular formation of the medulla, coordinates the motor mechanisms of vomit-... 

The effects of the ergot alkaloids on the central nervous system are very diverse as sites of action are situated in the vasomotor center and the cardiac inhibitory center in the medulla oblongata as well as in the sympathetic structures of the diencephalon, particularly the hypothalamus. The inhibition of the vasomotor center and of tire baroceptive reflexes and the stimulation of the vagal nuclei are resppfisible for the vasodilator, hypotensive, and bradycardic effects, especially in the case of the peptide type of alkaloid. Some also have a stimulating effect on the vomiting center. 

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