Emesis, drugs

Aapro MS 5-HT3 receptor antagonists an overview of their present status and future potential in cancer therapy-induced emesis. Drugs 42 551-568, 1991... 

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... 

These include atropine, scopolamine (hyoscine), trihexyphenidyl (benzhexol) and benzatropine. They block central muscarinic receptors involved in various afferent pathways of the vomiting reflex (Fig. 1). They have been used to control motion sickness, emesis in Meniere s disease and postoperative vomiting. Currently, hyoscine is largely restricted to the treatment of motion sickness where it has a fast onset of action but a short duration (4-6 h). Administration of hyoscine by transdermal patch produces a prolonged, low-level release of the drug with minimal side effects. To control postoperative vomiting, it should be applied >8 h before emesis is anticipated. 

The nurse monitors the patient for signs and symptoms of acute salicylate toxicity or salicylism (see Display 17-1). Initial treatment includes induction of emesis or gastric lavage to remove any unabsorbed drug from the stomach. Activated charcoal diminishes salicylate absorption if given within 2 hours of ingestion. Further therapy is supportive (reduce hyperthermia and treat severe convulsions with diazepam). Hemodialysis is effective in removing Hie salicylate but is used only in patients with severe salicylism. 

The nurse positions the patient on his or her side before or immediately after the drug is given. When emesis occurs, the nurse suctions the patient as needed and observes closely for the possible aspiration of vomitus. The nurse monitors vital signs every 5 to 10 minutes until signs are stable ... 

Substance P, an undecapeptide, is abundant both in the periphery and in the central nervous system. It is usually co-localized with one of the classical neurotransmitters, most commonly serotonin. Substance P is thought to have a role in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. The substance-P-preferring receptor neurokinin-1 has been focused on most intensively in drug development, and existing... 

An important advance in this field has been made by the discovery of selective serotonin (5-HT3) receptor antagonists that are effective inhibitors of cytotoxic drug-induced emesis in laboratory animals. The new agents have been found to be free of the undesirable side-effects associated with dopaminergic blockade and have shown significant protection from emesis in early clinical trials. 

There are a few reports on possible sites of action of 5-HT3 antagonists. Low doses of zacopride administered directly into the fourth ventricle (i.c.v.) antagonized cisplatin (i.v.[-induced emesis in the cat [108]. A similar antagonism was demonstrated when routes of drug administration were interchanged. Similarly, GR 38032F, GR 65630 and MDL 72222, administered i.c.v. onto the area postrema at very low doses, antagonized cisplatin-induced... 

When one requires complete assurance that an uncooperative subject has actually received the drug and has not rejected it (e.g., via forced emesis). 

A direct reaction of activation is exemplified by the NK receptor antagonist L-754,030 (9.78) developed as an i.v. drug against emesis, migraine, and chronic pain. Because the compound has a low water solubility unfavorable for i.v. administration, a phosphoramidate prodrug (9.77) has been examined [152], This compound hydrolyzed rapidly under acidic conditions. More importantly, it was rapidly converted to L-754,030 in rat blood but was... 

After decontamination by emesis or lavage, patients should be carefully monitored for alterations in liver and kidney function, and treated symptomatically if necesseray. Seizures can be treated with anti-convulsant drugs. Because the toxin produces a deficiency of y-amino-butyric acid (GABA), specific treatment with pyridoxine (vitamin Bg) has been recommended. 

Severe emesis - Severe emesis should not be treated with an antiemetic drug alone where possible, establish cause of vomiting. Direct primary emphasis toward restoration of body fluids and electrolyte balance, and relief of fever and causative disease process. Avoid overhydration which may result in cerebral edema. 

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