Emesis

Even after an effective regimen for prophylaxis, nausea or vomiting can begin again or persist 24 h or more after chemotherapy, particularly with cisplatin. Concurrent use of oral dexamethasone (8 mg twice daily for 2 d, then 4 mg twice daily for 2 d) and oral metoclopramide (0.5 mg/kg four times daily for 4 d) has been effective for this condition. Ondansetron alone has not been effective for treatment of delayed emesis following high doses of cisplatin. 

Polar substances cannot reach the emetic center itself because it is protected by the blood-brain barrier. However, they can indirectly excite the center by activating chemo-receptors in the area postrema or receptors on peripheral vagal nerve endings. 

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p.110) and Hq-antihistaminics (p.118) of the diphenylmethane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all para-sympatholytics or antihistaminics. The ef -cacy of the drugs mentioned depends on the actual situation of the individual (gastric filling, ethanol consumption), environmental conditions (e.g., the behavior of fellow trav-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

Pregnancy vomiting is prone to occur in the first trimester thus, pharmacotherapy would coincide with the period of maximal fetal vulnerability to chemical injury. Accordingly, antiemetics (antihistaminics, or neuroleptics if required p.232) should be used only when continuous vomiting threatens to disturb electrolyte and water balance to a degree that places the fetus at risk. 

The synthetic cannabinoids dronabinol and nabilone have antiemetic effects that may benefit AIDS and cancer patients. 

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Serious hepatotoxicity of tacrine has been documented. More recent data suggest, however, that this toxicity can be reduced by carehiUy monitoring semm alanine aminotransferase levels (125). The side effects of tacrine also include gastrointestinal disturbances and emesis, and alternative AChE therapies are being advanced. Velnacrine (20), a metaboUte of tacrine, was expected to have reduced hepatotoxicity. However, its limited efficacy and side-effect profile, which includes dmg-related hematological changes, caused it to be dropped from further development. 

CI-979 (29) is a balanced muscarinic agonist having equal affinities for cloned ml and m2 receptors (144). However, unlike prototypical muscarinic compounds such as (25), (29) increases central muscarinic tone, as indicated by behavioral and electroencephalogram (EEG) parameters, at doses lower than those requited to produce gastrointestinal effects (144). CI-979 is well tolerated in humans up to a dose of 1 mg. Dose-limiting side effects such as stomach pain and emesis were observed at a dose of 2 mg. 

Treatment for acute exposure to benzene vapor involves removing the subject from the affected area, followed by artificial respiration with oxygen intubation and cardiac monitors may be necessary for severe acute exposures (125,127). Because of its low surface tension, benzene poses a significant aspiration hazard if the liquid enters the lungs. Emesis is indicated in alert patients if more than 1 mL of benzene per kg of body weight has been ingested and less than two hours have passed between ingestion and treatment (127). 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

Because of emesis, it is unlikely that appreciable quantities of most common soaps and detergents could be ingested accidentally. 

Asarum europeum L. According to Abdul menev, the root of this plant contains 1-7 per cent, of imcharacterised alkaloid, asarine. The root produces in frogs, rabbits and dogs, acceleration of respiration, nausea and emesis the cardiac activity of the leaves is thought to be due to a glucoside. (Farmatsiya, 1945, 8, No. 4, p. 39 Chem. Abstr., 1946, 40, 7411.)... 

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

Diuretics, laxatives, diarrohea, emesis Electrolyte derangements ... 

Emesis is the forcefiil involuntary expulsion of the stomach contents through the mouth. It is a reflex response that may be initiated by a number of stimuli. 

Retching is the process of emesis but without the actual expulsion of any of the stomach contents. 

In the gastrointestinal tract, drugs or toxins, as well as mechanical stimulation, induce emesis by activation of sensory receptors on afferent neurons in the vagus and sympathetic nerves. Information is relayed to the vomiting centre via the nucleus tractus solitarius... 

Impulses from the vestibular apparatus in the labyrinth are conducted via the vestibular nucleus and cerebellum to the vomiting centre. Abnormal stimulation of the vestibular apparatus is involved in motion sickness and emesis, associated with Menieres disease. 

Emesis. Figure 1 Afferent pathways involved in vomiting. Some stimuli for initiation of vomiting from the various locations are shown in the boxes. The presence of receptors at a particular location does not imply that they are necessarily involved in normal transmission of the vomiting reflex. 

The most widely used emetic is syrup of ipecac, containing the alkaloids, emetine and cq haeline. Emetine induces vomiting by activation of sensory neurons in the vagus and sympathetic nerves to the stomach and centrally in the medulla, possibly at the CTZ. The release of serotonin and SP may be involved as 5-HT3 and NKi receptor antagonists prevent emesis induced... 

Cytotoxics also cause cellular damage and the release of serotonin and other mediators from enterochromaffin cells. There is conflicting evidence regarding whether 5-HT3 receptors in the medulla are activated also during chemotherapy and contribute to production of emesis. Currently, the weight of evidence favours peripheral 5-HT3 receptors, with minor involvement of central receptors. 

Opioids act on the area postrema and/or the NTS via p or 8 receptors to produce emesis. Also, ambulatory patients receiving opioids are more affected than those confined to bed, suggesting a vestibular component in the effect. The emetic action of opioids is complicated by an antiemetic action, possibly involving two receptors at the NTS or the vomiting centre. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

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