Cyclic vomiting syndrome: timing, targets, and treatment--a basic science perspective.
Nausea and vomiting are both elements of the system that evolved to defend the body against toxins accidentally ingested with the food. When they are induced by an ingested toxin, they are considered to be an appropriate response, but in many clinical settings (eg, anticancer chemotherapy, anesthesia and surgery, raised intracranial pressure) both responses are inappropriate in that the vomiting does not remove the cause and the nausea may lead to aversion to further treatment. Cyclic vomiting syndrome (CVS) is a particularly intense and prolonged example of inappropriate activation of this protective reflex. This review argues that insights into the pattern of emesis in CVS can be gained by examining the basic unit (quantum) of emesis, the emetic episode usually comprising retches followed by a vomit. Two (of several) possible mechanisms for the induction of the intense vomiting in CVS are discussed: (1) defects in intrinsic pathways (eg, opioid neurons) that may modulate the brain-stem emetic mechanisms, and (2) defects in the regulation of cellular mechanisms (eg, cAMP, ion channels) in cells at critical locations in the emetic pathway (eg, nucleus tractus solitarius, area postrema). If it is not possible to identify the causal mechanism of CVS, then will it be possible to treat CVS? This question is discussed in the context of the identification of universal or broad-spectrum antiemetic agents with recent preclinical studies with neurokinin-1 receptor antagonists reviewed to illustrate that such an approach is feasible.
Andrews
P L
PL
Department of Physiology, St. George's Hospital Medical School, London, UK.
D000293:Adolescent; D000328:Adult; D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D064729:Neurokinin-1 Receptor Antagonists; D010507:Periodicity; D011789:Quantum Theory; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013577:Syndrome; D014839:Vomiting / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D011957:Receptors, Opioid