title: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same?
abstract: Selective serotonin 5-HT(3) receptor antagonists have proven safe and effective for the management of postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron and tropisetron selectively and competitively bind to 5-HT(3) receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the CNS involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii. Despite their shared mechanism of action, 5-HT(3) receptor antagonists have different chemical structures and exhibit differences in receptor binding affinity, dose response and duration of effect. Furthermore, although dolasetron, granisetron, ondansetron and tropisetron are all extensively metabolised by the cytochrome P450 (CYP) system, different components of this system predominate in the metabolism of each of these agents. Hence, although these agents are considered equally effective in the overall population, their pharmacokinetic and pharmacodynamic differences may explain the variability in individual responses to these drugs. This review discusses the pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron, and the clinical implications of differences in their profiles.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. gan00001@mc.duke.edu
authors.forename: Tong J
authors.initials: TJ
authors.lastname: Gan
mesh_terms: D000932:Antiemetics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D020250:Postoperative Nausea and Vomiting / Q000188:drug therapy*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000932:Antiemetics; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists
references.citation: Anesth Analg. 2002 Jun;94(6):1553-7, table of contents
references.pmid: 12032025
references.citation: Am J Health Syst Pharm. 1997 May 15;54(10):1172-6
references.pmid: 9161624
references.citation: Eur J Clin Pharmacol. 1999 May;55(3):177-84
references.pmid: 10379632
references.citation: Anesthesiology. 1996 Nov;85(5):1076-85
references.pmid: 8916825
references.citation: J Cardiovasc Pharmacol. 1996 Jul;28(1):53-9
references.pmid: 8797136
references.citation: Br J Anaesth. 1996 Apr;76(4):515-8
references.pmid: 8652323
references.citation: J Clin Anesth. 1999 Sep;11(6):453-9
references.pmid: 10526822
references.citation: Br J Clin Pharmacol. 2001 Dec;52(6):705-7
references.pmid: 11736884
references.citation: Eur J Cancer. 1992;28A Suppl 1:S2-6
references.pmid: 1320915
references.citation: Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):43-50
references.pmid: 8839677
references.citation: J Cardiovasc Pharmacol. 1993 Sep;22(3):499-505
references.pmid: 7504144
references.citation: Acta Anaesthesiol Scand. 2001 Jan;45(1):4-13
references.pmid: 11152031
references.citation: Anesth Analg. 1997 Feb;84(2):325-30
references.pmid: 9024022
references.citation: Anaesth Intensive Care. 1999 Oct;27(5):471-6
references.pmid: 10520386
references.citation: Clin Oncol (R Coll Radiol). 1995;7(6):371-2
references.pmid: 8590698
references.citation: Acta Anaesthesiol Scand. 1997 Aug;41(7):914-22
references.pmid: 9265937
references.citation: Drug Saf. 1996 Mar;14(3):181-97
references.pmid: 8934580
references.citation: J Pharmacol Exp Ther. 2000 Nov;295(2):614-20
references.pmid: 11046096
references.citation: Acta Oncol. 1995;34(5):637-40
references.pmid: 7546831
references.citation: Eur J Cancer. 1990;26 Suppl 1:S12-5
references.pmid: 2169778
references.citation: Br J Anaesth. 1999 Nov;83(5):761-71
references.pmid: 10690140
references.citation: Br J Anaesth. 2002 Dec;89(6):810-3
references.pmid: 12453921
references.citation: Anesth Analg. 1998 Mar;86(3):496-500
references.pmid: 9495400
references.citation: Eur J Pharmacol. 1990 Jun 12;188(6):301-12
references.pmid: 2164935
references.citation: J Clin Pharmacol. 1995 Jul;35(7):705-12
references.pmid: 7560251
references.citation: J Clin Oncol. 1996 Aug;14(8):2242-9
references.pmid: 8708713
references.citation: Anesth Analg. 2001 Dec;93(6):1626
references.pmid: 11726465
references.citation: Drugs. 1998 Feb;55(2):173-89
references.pmid: 9506240
references.citation: Br J Hosp Med. 1995 Apr 5-18;53(7):327-30
references.pmid: 7788070
references.citation: J Clin Oncol. 2002 Jun 15;20(12):2805-11
references.pmid: 12065557
references.citation: Clin Ther. 2001 Jun;23(6):932-8
references.pmid: 11440292
references.citation: J Clin Anesth. 1997 Dec;9(8):658-63
references.pmid: 9438895
references.citation: Drug Metab Dispos. 1994 Mar-Apr;22(2):269-74
references.pmid: 8013282
references.citation: Acta Pharmacol Sin. 2001 Mar;22(3):283-8
references.pmid: 11742579
references.citation: Anesth Analg. 1997 Feb;84(2):331-6
references.pmid: 9024023
references.citation: Drug Metab Dispos. 1995 Nov;23(11):1225-30
references.pmid: 8591723
references.citation: Clin Pharmacol Ther. 1992 Jan;51(1):51-5
references.pmid: 1531044
references.citation: Anesth Analg. 1994 Nov;79(5):983-6
references.pmid: 7978420
references.citation: J Pharmacol Exp Ther. 1988 Jun;245(3):773-8
references.pmid: 2455036
references.citation: Oncologist. 2002;7(1):65-72
references.pmid: 11854548
references.citation: Acta Anaesthesiol Scand. 2002 May;46(5):519-24
references.pmid: 12027845
references.citation: Anesth Analg. 2003 Jul;97(1):62-71, table of contents
references.pmid: 12818945
references.citation: Br J Clin Pharmacol. 1994 Dec;38(6):557-66
references.pmid: 7888294
references.citation: Anesth Analg. 1995 May;80(5):970-4
references.pmid: 7726441
references.citation: Can J Anaesth. 2000 Oct;47(10):1008-18
references.pmid: 11032279
references.citation: Br J Pharmacol. 2000 Jul;130(5):1031-6
references.pmid: 10882387
references.citation: Br J Cancer. 2001 Oct 19;85(8):1099-101
references.pmid: 11710819
references.citation: Anaesthesia. 1994 Jan;49 Suppl:2-5
references.pmid: 8129158
references.citation: Eur J Cancer. 1996 May;32A(5):807-13
references.pmid: 9081358
references.citation: Drug Metab Dispos. 1996 May;24(5):602-9
references.pmid: 8723743
references.citation: BMC Anesthesiol. 2001;1(1):2
references.pmid: 11734064
references.citation: Anesthesiology. 1997 Dec;87(6):1277-89
references.pmid: 9416710
references.citation: Anesth Analg. 2000 Jun;90(6):1352-8
references.pmid: 10825320
references.citation: Neuropharmacology. 1993 Aug;32(8):729-35
references.pmid: 8413836
references.citation: Anticancer Drugs. 1998 Jun;9(5):381-5
references.pmid: 9660533
references.citation: Anesth Analg. 1998 Mar;86(3):617-23
references.pmid: 9495426
references.citation: Eur J Clin Pharmacol. 1996;51(1):79-85
references.pmid: 8880056
references.citation: J Physiol. 1982 Feb;323:543-67
references.pmid: 7097585
references.citation: Eur J Anaesthesiol. 1998 Nov;15(6):676-85
references.pmid: 9884853
references.citation: Drugs. 2000 Feb;59(2):213-43
references.pmid: 10730546
references.citation: Drug Metab Dispos. 1992 Jul-Aug;20(4):603-7
references.pmid: 1356742
references.citation: Can J Anaesth. 1996 Mar;43(3):226-31
references.pmid: 8829860
references.citation: Anaesthesist. 2002 Oct;51(10):805-14
references.pmid: 12395171
references.citation: Br J Cancer. 2002 May 20;86(10):1662-3; author reply 1664
references.pmid: 12085221
references.citation: Anesth Analg. 2001 May;92(5):1319-21
references.pmid: 11323369
references.citation: Cancer J. 2002 Sep-Oct;8(5):405-14
references.pmid: 12416899