Pharmacy & Therapeutics - October 2008 - (Page PP6)

PRODUCT PROFILER: Granisetron Transdermal Delivery System Current Drug Therapy Options And Treatment Guidelines togenic substances, such as chemotherapeutic agents, The mechanism of CINV involves a complex interin the blood and cerebrospinal fluid.5 The CTZ sends action between neurotransmitters and receptors in impulses to the vomiting center, which initiates the both the central nervous system (CNS) and the periphvomiting cascade by sending efferent impulses to the eral nervous system (Figure 1).5 This process is initirespiratory, vasomotor, and salivary centers as well as ated by the stimulation of dopamine, opiate, histamine, to cranial nerves VIII and X.5 Impulses are then sent to acetylcholine, neurokinin-1 (NK1) or serotonin (5-HT) the abdominal muscles, the diaphragm, the stomach, and the esophagus, resulting in emesis.5 receptors (see Figure 1).5 Dopamine type-2 (D2) and The role of the limbic system in emesis is less underserotonin type-3 (5-HT3) receptors seem to have the most important roles in CINV.5 Therefore, pharmastood. The limbic region of the brain, located within the cerebral cortex, is responsible for anticipatory or cotherapy for the treatment and prevention of CINV is learned responses, and it can initiate emesis from aimed primarily at blocking the receptors of these neuchemotherapy indirectly.5 rotransmitters. A final common pathway for emesis remains to be During the past two decades, results from some studidentified. Antiemetic agents block different neuronal ies have suggested that substance P might also be a relpathways and exert their effects at varying points durevant neurotransmitter in CINV. It belongs to a group ing the course of emesis, often providing synergistic of peptides (the tachykinins), which have several regeffects when they are used together. ulatory functions. Three mammalian tachykinins have been isolated: substance P, NK-A, and NK-B, which preferentially bind to receptors NK-1, NK2, and NK-3, respectively. NK-1 receptors are CTZ GI tract widely distributed throughout the CNS, including Cortex D2, 5-HT3, NK1, M 5-HT3, NK1 the area postrema and the nucleus tractus solitarius; they are also located in peripheral sites, such as the gastrointestinal (GI) tract. EvaluaNTS tion of selective NK-1–receptor antagonists in D2, H1, 5-HT3, animal models reveals significant antiemetic effiNK1, M cacy across a wide spectrum of emetic stimuli. It also appears that the NK-1 antagonists have a central site of action.14 Vomiting center One recognized mechanism by which cancer chemotherapy and radiation therapy cause emesis is the ability of these modalities to cause Salivatory center enterochromaffin cells that line the GI tract to Respiratory center release serotonin.5 The serotonin subsequently Vasomotor center binds to vagal afferent 5-HT3 receptors in the GI Cranial nerves tract, which in turn send impulses to the vomiting center in the lateral reticular formation of the medulla in the brain.5 The vomiting center is a Effector organs physiological entity that consists of intertwined neural networks in the nucleus tractus solitarii of Figure 1 Pathways and neurotransmitter receptors in chemotherthe medulla oblongata.5 Impulses are also sent apy-induced nausea and vomiting. CTZ = chemoreceptor trigger to the vomiting center from the chemoreceptor zone; D2 = dopamine type-2 receptor; GI = gastrointestinal; trigger zone (CTZ), the brain cortex, and the 5-HT3 = serotonin type-3 receptor; H1 = histamine type-1 receptor; vestibular apparatus.5 The CTZ, which is believed M = muscarinic receptor; NK1 = tachykinin neurokinin type-1 to play an important role in CINV, is located in the receptor; NTS = nucleus tractus solitarius. (Originally published in area postrema in the floor of the fourth ventricle.5 American Journal of Health-System Pharmacy 1999;56:734. © 1999, American Society of Health-System Pharmacists, Inc. All Because the CTZ is outside the blood–brain barrights reserved. Reprinted with permission. (R0827)5 rier, it can be easily accessed by circulating eme6 PATHOPHYSIOLOGY

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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