{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T05:21:41Z","timestamp":1741411301856,"version":"3.38.0"},"reference-count":26,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To characterize the signalment, dose response, and clinical signs of diphenhydramine toxicosis in dogs.<\/jats:p>\n<jats:p><jats:bold>DESIGN<\/jats:bold> Retrospective case series.<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> 621 dogs with diphenhydramine exposure.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> The electronic medical record database for an animal poison control center was reviewed from January 2008 through December 2013 to identify dogs that had ingested or been injected with diphenhydramine. Information extracted from the records and evaluated included the signalment, clinical signs observed, and estimated exposure dose of diphenhydramine. Clinical signs were categorized as none, mild, moderate, and severe.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> The mean \u00b1 SEM age of dogs was 3.6 \u00b1 0.1 years (range, 0.1 to 16 years). Diphenhydramine exposure was by ingestion for 581 (93.6%) dogs and injection for 40 (6.4%) dogs. Only 146 (23.5%) dogs developed \u2265 1 clinical signs of toxicosis, the most common of which were associated with the nervous (lethargy, hyperactivity, agitation, hyperthermia, ataxia, tremors, and fasciculations) or cardiovascular (tachycardia) systems, and 3 dogs died. Although the presence and extent of clinical signs varied greatly among dogs, the exposure dose of diphenhydramine was positively associated with the severity of clinical signs in a dose-dependent manner regardless of the route of exposure (ingestion or injection).<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Results indicated that dogs exposed to diphenhydramine developed clinical signs of toxicosis fairly infrequently, and those clinical signs were generally mild and primarily affected the neurologic and cardiovascular systems. Supportive treatment for diphenhydramine toxicosis should be administered on the basis of the clinical signs observed.<\/jats:p>","DOI":"10.2460\/javma.249.1.77","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T19:00:53Z","timestamp":1466103653000},"page":"77-82","source":"Crossref","is-referenced-by-count":4,"title":["Diphenhydramine exposure in dogs: 621 cases (2008\u20132013)"],"prefix":"10.2460","volume":"249","author":[{"given":"Alisha C.","family":"Worth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina A.","family":"Wismer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Dorman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Clin Toxicol (Phila)","doi-asserted-by":"publisher","first-page":"945","DOI":"10.3109\/15563650.2010.527850","article-title":"Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose","volume":"48","author":"Jang","year":"2010"},{"key":"ref2","series-title":"Cochrane Database Syst Rev","first-page":"CD001267","article-title":"Antihistamines for the common cold","volume":"3","author":"Sutter","year":"2003"},{"series-title":"OTC Sales by Category\u20142010\u20132013","key":"ref3"},{"key":"ref4","series-title":"Saunders handbook of veterinary drugs: small and large animals","first-page":"243","article-title":"Diphenhydramine hydrochloride","author":"Papich","year":"2011"},{"key":"ref5","series-title":"Clin Exp Allergy","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1046\/j.0954-7894.2002.01314.x","article-title":"H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects","volume":"32","author":"Leurs","year":"2002"},{"key":"ref6","series-title":"Allergy Asthma Proc","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2500\/aap.2007.28.3015","article-title":"Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review","volume":"28","author":"Banerji","year":"2007"},{"key":"ref7","series-title":"Pharmacol Rev","first-page":"253","article-title":"International Union of Pharmacology. XIII. Classification of histamine receptors","volume":"49","author":"Hill","year":"1997"},{"key":"ref8","series-title":"J Investig Allergol Clin Immunol","first-page":"17","article-title":"H1 antihistamines and benzodiazepines. Pharmacological interactions and their impact on cerebral function","volume":"23","author":"Montoro","year":"2013"},{"key":"ref9","series-title":"Clin Allergy Immunol","first-page":"337","article-title":"H1-antihistamines and the central nervous system","volume":"17","author":"Welch","year":"2002"},{"key":"ref10","series-title":"Clin Toxicol (Phila)","doi-asserted-by":"publisher","first-page":"949","DOI":"10.3109\/15563650.2013.863906","article-title":"2012 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th annual report","volume":"51","author":"Mowry","year":"2013"},{"key":"ref11","series-title":"Can Vet J","first-page":"1089","article-title":"Fatal diphenhydramine poisoning in a dog","volume":"55","author":"Buchweitz","year":"2014"},{"key":"ref12","series-title":"Hum Exp Toxicol","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1191\/096032700671040438","article-title":"Dose-dependent toxicity of diphenhydramine overdose","volume":"19","author":"Radovanovic","year":"2000"},{"key":"ref13","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0006-8993(00)03041-9","article-title":"Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats","volume":"887","author":"Kamei","year":"2000"},{"key":"ref14","series-title":"J Vet Intern Med","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1939-1676.2011.0695.x","article-title":"Mortality in North American dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death","volume":"25","author":"Fleming","year":"2011"},{"key":"ref15","series-title":"J Am Anim Hosp Assoc","doi-asserted-by":"publisher","first-page":"81","DOI":"10.5326\/0410081","article-title":"AAHA senior care guidelines for dogs and cats","volume":"41","author":"Epstein","year":"2005"},{"series-title":"Diphenhydramine","key":"ref16"},{"article-title":"Body weight studies","year":"2011","series-title":"Exposure factors handbook","key":"ref17"},{"key":"ref18","series-title":"J Med Toxicol","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s13181-011-0157-3","article-title":"Case files of the medical toxicology fellowship at Drexel University. Rhabdomyolysis and compartment syndrome following acute diphenhydramine overdose","volume":"7","author":"Vearrier","year":"2011"},{"key":"ref19","series-title":"Toxicol Lett","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/0378-4274(87)90137-8","article-title":"Interaction of diphenhydramine with cholinesterase inhibitors in mice","volume":"37","author":"Mohammad","year":"1987"},{"key":"ref20","series-title":"J Neurochem","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1471-4159.2008.05361.x","article-title":"Cocaine-like neurochemical effects of antihistaminic medications","volume":"106","author":"Tanda","year":"2008"},{"key":"ref21","series-title":"J Poult Sci","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2141\/jpsa.011050","article-title":"Acute toxicity and neurobehavioral effects of diphenhydramine in chicks","volume":"49","author":"Mohammad","year":"2012"},{"key":"ref22","series-title":"Kirk's current veterinary therapy XV","first-page":"909","article-title":"Over-the-counter drug toxicosis: H1-antihistamines","author":"Dorman","year":"2014"},{"key":"ref23","series-title":"Psychiatry Clin Neurosci","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1111\/j.1440-1819.2011.02234.x","article-title":"Diphenhydramine overdose mimicking serotonin syndrome","volume":"65","author":"Tanaka","year":"2011"},{"key":"ref24","series-title":"Clin Pharmacokinet","doi-asserted-by":"publisher","first-page":"477","DOI":"10.2165\/00003088-198510060-00002","article-title":"Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines)","volume":"10","author":"Paton","year":"1985"},{"key":"ref25","series-title":"J Clin Pharmacol","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/j.1552-4604.1990.tb01871.x","article-title":"Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children","volume":"30","author":"Simons","year":"1990"},{"key":"ref26","series-title":"Xenobiotica","doi-asserted-by":"publisher","first-page":"893","DOI":"10.3109\/00498254.2014.903532","article-title":"Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and Beagle dogs","volume":"44","author":"Koyanagi","year":"2014"}],"container-title":["Journal of the American Veterinary Medical Association"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/249\/1\/javma.249.1.77.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/249\/1\/javma.249.1.77.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/javma\/249\/1\/javma.249.1.77.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T11:49:40Z","timestamp":1741348180000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/javma\/249\/1\/javma.249.1.77.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,1]]},"references-count":26,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.2460\/javma.249.1.77","relation":{},"ISSN":["0003-1488"],"issn-type":[{"type":"print","value":"0003-1488"}],"subject":[],"published":{"date-parts":[[2016,7,1]]}}}