Histamine and Emesis

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. 

Knowledge of the physiological role of histamine in the CNS and evidence for the existence of discrete neuronal networks that could be called histaminergic are still evolving. Histamine-mediated hypothermia, emesis, and hypertension have been shown to exist, and the well-known sedative effects of Hj antihistamines are centrally mediated. 

Dopamine receptors are found in high concentration in the area postrema, which contains the chemoreceptor trigger zone (CTZ). Histamine Hl-receptors are concentrated in the nucleus tractus solitarius, which processes information relating to emesis, and in the dorsal motor nucleus of the vagus. This nucleus and the nucleus ambiguus also contain muscarinic cholinergic receptors, and these initiate motor components of vomiting. 

Stealth liposomes Liposomal infusion reaction (hypoactivity, flushing, diarrhea, emesis, and decreased blood pressure seen following intravenous infusion in dogs) Transient effect (resolved within 1-2 hr). Biological significance is not apparent but the finding has been related to histamine release due to the infusion of a large amount of lipid 27... 

The vomiting centre and the nucleus of the tractus solitarius contain many muscarinic cholinergic and histamine receptors, and the CTZ is rich in dopamine receptors drugs that block these receptors are effective antiemetics. The precise role and location of S-HTj receptors (see ondansetron, below) in relation to emesis remains to be defined but both central and peripheral mechanisms may be involved. 

MOA Competitive antagonism of the smooth muscle stimulating actions of histamine on H, receptors. The central anticholinergic activity of antihistamines reduces symptoms of emesis and counteracts EPS associated with antipsychotic treatment. 

Histamine Hj-receptor antagonists are primarily useful for motion sickness and postoperative emesis. They act on vestibular afferents and within the brain stem. Cyclizine, hydroxyzine, promethazine, and diphenhydramine are examples of this class of agents. Cyclizine has additional anticholinergic effects that may be useful for patients with abdominal cancer. 

It exhibits a profile of pharmacological action very much identical to morphine, and differs exceptionally on two accounts, namely flrst-it does not cause emesis secondly, it does not release histamine. Its safety measure in frequency cases has not yet been fully understood. It is observed to cross the placental barrier therefore, its usage during labour may ultimately give rise to respiratory depression in the newly bom infant. However, Fentanyl s transient action after the parenteral administration is caused solely on account of redistribution, rather than to "metabolism" or "excretion". Hence, longer usage of this drug may cause in accumulation and toxicities. 

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