Cough, Cold, and Allergy Preparation Toxicity Medication
- Author: Laleh Gharahbaghian, MD; Chief Editor: Timothy E Corden, MD more...
Most patients with toxicity from cold, cough, or allergy preparations have good outcomes with simple observation and meticulous attention to supportive care. Activated charcoal can reduce absorption of the medication in patients who present early after ingestion. Benzodiazepines can be used for control of anxiety, agitation, and seizures. Limit treatment with physostigmine to severe cases.
GI decontamination with oral activated charcoal is selectively used in the emergency treatment of poisoning caused by some drugs and chemicals.
Activated charcoal is used in emergency treatment for poisoning caused by drugs and chemicals. A network of pores adsorbs 100-1000 mg of drug per gram. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine.
Activated charcoal achieves its maximum effect when administered within 30 minutes after ingestion of a drug or toxin. However, decontamination with activated charcoal may be considered in any patient who presents within 4 hours after the ingestion. Repeated doses may help to lower systemic levels of ingested compounds, especially sustained-release preparations. Activated charcoal does not dissolve in water. Supply it as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%).
Diazepam is indicated for the control of anxiety and agitation.
Diazepam is indicated for treatment of acute dystonic reactions caused by antihistamines, as well as for muscle activity and agitation associated with serotonin syndrome. Diazepam depresses all levels of the CNS (eg, limbic system and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). It is a third-line agent for agitation or seizures because of its shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.
A sedative hypnotic with short onset of effects and relatively long half-life, lorazepam is used to treat seizures. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic system and reticular formation. It is the drug of choice for seizure control because of a more prolonged anticonvulsant effects than diazepam or midazolam (4-6 h vs 1-3 h). It has an excellent safety profile, but the patient's blood pressure should be monitored after administration of this agent.
Midazolam is an alternative agent for termination of refractory status epilepticus. Compared with diazepam, midazolam has twice the affinity for benzodiazepine receptors; however, because it is water soluble, midazolam takes approximately 3 times longer than diazepam to achieve peak electroencephalographic effects. Thus, the clinician must wait 2-3 minutes to fully evaluate sedative effects before initiating a procedure or repeating the dose. This agent may be administered intramuscularly if vascular access cannot be obtained.
Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces the monosynaptic and polysynaptic reflexes. It suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and the action of other inhibitory transmitters.
Anticholinergic Toxicity Antidotes
Acetylcholinesterase inhibitors are indicated to reverse central and peripheral toxicity of anticholinergic substances.
Physostigmine is a reversible cholinesterase inhibitor that increases the concentration of acetylcholinesterase in the myoneural junction. It readily crosses the blood-brain barrier to produce desired CNS effects. This agent should not be given unless recommended by a regional poison control center or in direct consultation with a toxicologist.
Electrolyte Supplements, Parenteral
These agents alter the electrophysiologic mechanisms responsible for arrhythmia in patients with toxicity from cold, cough, or allergy medications.
Intravenous sodium bicarbonate, 100 mEq over 5 minutes, followed by continuous infusion used for its alkalization properties to maintain a serum pH of 7.5-7.55, has reversed hypotension and resulted in narrowing of the QRS complex in isolated case reports. Sodium bicarbonate is the first-line agent for patients with prolongation of QRS interval after an overdose of an antihistamine with quinidinelike effects.
Magnesium acts as an antiarrhythmic agent and diminishes the frequency of premature ventricular contractions (PVCs), particularly those resulting from acute ischemia. Deficiency in this electrolyte can precipitate refractory ventricular fibrillation (VF) and is associated with sudden cardiac death. Magnesium sulfate is the first-line agent in the treatment of antihistamine-associated torsade de pointes.
Jo YI, Song JO, Park JH, Koh SY, Lee SM, Seo TH, et al. Risk factors for rhabdomyolysis following doxylamine overdose. Hum Exp Toxicol. 2007 Aug. 26(8):617-21. [Medline].
Vernacchio L, Kelly JP, Kaufman DW, Mitchell AA. Cough and cold medication use by US children, 1999-2006: results from the slone survey. Pediatrics. 2008 Aug. 122(2):e323-9. [Medline].
US allergy market affecting the daily life of millions of Americans. Companies and Markets.com. Available at http://www.companiesandmarkets.com/News/Healthcare-and-Medical/US-allergy-market-affecting-the-daily-life-of-millions-of-Americans/NI6717. Accessed: August 21, 2013.
Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. 2000 Dec 21. 343(25):1826-32. [Medline].
Spiller HA, Beuhler MC, Ryan ML, Borys DJ, Aleguas A, Bosse GM. Evaluation of changes in poisoning in young children: 2000 to 2010. Pediatr Emerg Care. 2013 May. 29(5):635-40. [Medline].
Mazer-Amirshahi M, Reid N, van den Anker J, Litovitz T. Effect of Cough and Cold Medication Restriction and Label Changes on Pediatric Ingestions Reported to United States Poison Centers. J Pediatr. 2013 Jun 12. [Medline].
Yin HS, Parker RM, Wolf MS, et al. Health literacy assessment of labeling of pediatric nonprescription medications: examination of characteristics that may impair parent understanding. Acad Pediatr. 2012 Jul-Aug. 12(4):288-96. [Medline].
Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2012 Aug 15. 8:CD001831. [Medline].
Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radar--pediatric cough and cold medications. N Engl J Med. 2007 Dec 6. 357(23):2321-4. [Medline].
Revised product labels for pediatric over-the-counter cough and cold medicines. MMWR Morb Mortal Wkly Rep. 2008 Oct 31. 57(43):1180. [Medline].
[Guideline] Ostroff C, Lee CE, McMeekin J. Unapproved prescription cough, cold, and allergy drug products: recent US Food and Drug Administration regulatory action on unapproved cough, cold, and allergy medications. Chest. 2011 Aug. 140(2):295-300. [Medline].
Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan. 129(1 Suppl):1S-23S. [Medline]. [Full Text].
Yanai K, Rogala B, Chugh K, Paraskakis E, Pampura AN, Boev R. Safety considerations in the management of allergic diseases: focus on antihistamines. Curr Med Res Opin. 2012 Apr. 28(4):623-42. [Medline].
Ly KS, Letavic MA, Keith JM, Miller JM, Stocking EM, Barbier AJ, et al. Synthesis and biological activity of piperazine and diazepane amides that are histamine H3 antagonists and serotonin reuptake inhibitors. Bioorg Med Chem Lett. 2008 Jan 1. 18(1):39-43. [Medline].
Sasho S, Seishi T, Kawamura M, Hirose R, Toki S, Shimada JI. Diamine derivatives containing imidazolidinylidene propanedinitrile as a new class of histamine H3 receptor antagonists. Part I. Bioorg Med Chem Lett. 2008 Apr 1. 18(7):2288-91. [Medline].
Zhao C, Sun M, Bennani YL, Gopalakrishnan SM, Witte DG, Miller TR, et al. The alkaloid conessine and analogues as potent histamine H3 receptor antagonists. J Med Chem. 2008 Sep 11. 51(17):5423-30. [Medline].
Sasaki T, Takahashi T, Nagase T, Mizutani T, Ito S, Mitobe Y, et al. Synthesis, structure-activity relationships, and biological profiles of a dihydrobenzoxathiin class of histamine H(3) receptor inverse agonists. Bioorg Med Chem Lett. 2009 Aug 1. 19(15):4232-6. [Medline].
Covel JA, Santora VJ, Smith JM, Hayashi R, Gallardo C, Weinhouse MI, et al. Design and evaluation of novel biphenyl sulfonamide derivatives with potent histamine H(3) receptor inverse agonist activity. J Med Chem. 2009 Sep 24. 52(18):5603-11. [Medline].
Josef KA, Aimone LD, Lyons J, Raddatz R, Hudkins RL. Synthesis of constrained benzocinnolinone analogues of CEP-26401 (irdabisant) as potent, selective histamine H3 receptor inverse agonists. Bioorg Med Chem Lett. 2012 Jun 15. 22(12):4198-202. [Medline].
Stocking EM, Letavic MA. Histamine H3 antagonists as wake-promoting and pro-cognitive agents. Curr Top Med Chem. 2008. 8(11):988-1002. [Medline].
Sander K, Kottke T, Stark H. Histamine H3 receptor antagonists go to clinics. Biol Pharm Bull. 2008 Dec. 31(12):2163-81. [Medline].
Medhurst SJ, Collins SD, Billinton A, Bingham S, Dalziel RG, Brass A, et al. Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain. Pain. 2008 Aug 15. 138(1):61-9. [Medline].
Bembenek SD, Keith JM, Letavic MA, Apodaca R, Barbier AJ, Dvorak L, et al. Lead identification of acetylcholinesterase inhibitors-histamine H3 receptor antagonists from molecular modeling. Bioorg Med Chem. 2008 Mar 15. 16(6):2968-73. [Medline].
Masaki T, Yoshimatsu H. Therapeutic approach of histamine H3 receptors in obesity. Recent Pat CNS Drug Discov. 2007 Nov. 2(3):238-40. [Medline].
Deng C, Weston-Green K, Huang XF. The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain?. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1. 34(1):1-4. [Medline].
Beghdadi W, Porcherie A, Schneider BS, Morisset S, Dubayle D, Peronet R, et al. Histamine H(3) receptor-mediated signaling protects mice from cerebral malaria. PLoS One. 2009 Jun 23. 4(6):e6004. [Medline]. [Full Text].
Alleva L, Tirelli E, Brabant C. Therapeutic potential of histaminergic compounds in the treatment of addiction and drug-related cognitive disorders. Behav Brain Res. 2013 Jan 15. 237:357-68. [Medline].
Bhowmik M, Khanam R, Vohora D. Histamine H3 receptor antagonists in relation to epilepsy and neurodegeneration: a systemic consideration of recent progress and perspectives. Br J Pharmacol. 2012 Dec. 167(7):1398-414. [Medline]. [Full Text].
Vohora D, Bhowmik M. Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: relevance to Alzheimer's disease, ADHD, schizophrenia, and drug abuse. Front Syst Neurosci. 2012. 6:72. [Medline]. [Full Text].
Altenbach RJ, Adair RM, Bettencourt BM, Black LA, Fix-Stenzel SR, Gopalakrishnan SM, et al. Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands. J Med Chem. 2008 Oct 23. 51(20):6571-80. [Medline].
Kiss R, Kiss B, Könczöl A, Szalai F, Jelinek I, László V, et al. Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. J Med Chem. 2008 Jun 12. 51(11):3145-53. [Medline].
Tiligada E, Zampeli E, Sander K, Stark H. Histamine H3 and H4 receptors as novel drug targets. Expert Opin Investig Drugs. 2009 Oct. 18(10):1519-31. [Medline].
Larbi EB. Drug-induced rhabdomyolysis. Ann Saudi Med. 1998 Nov-Dec. 18(6):525-30. [Medline].
Pelle E, McCarthy J, Seltmann H, Huang X, Mammone T, Zouboulis CC, et al. Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes. J Invest Dermatol. 2008 May. 128(5):1280-5. [Medline].
Devillier P, Roche N, Faisy C. Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008. 47(4):217-30. [Medline].
De Vos C, Mitchev K, Pinelli ME, Derde MP, Boev R. Non-interventional study comparing treatment satisfaction in patients treated with antihistamines. Clin Drug Investig. 2008. 28(4):221-30. [Medline].
Walsh GM. A review of the role of levocetirizine as an effective therapy for allergic disease. Expert Opin Pharmacother. 2008 Apr. 9(5):859-67. [Medline].
Scherer CR, Lerche C, Decher N, Dennis AT, Maier P, Ficker E, et al. The antihistamine fexofenadine does not affect I(Kr) currents in a case report of drug-induced cardiac arrhythmia. Br J Pharmacol. 2002 Nov. 137(6):892-900. [Medline]. [Full Text].
Soldovieri MV, Miceli F, Taglialatela M. Cardiotoxic effects of antihistamines: from basics to clinics (...and back). Chem Res Toxicol. 2008 May. 21(5):997-1004. [Medline].
Izumi N, Mizuguchi H, Umehara H, Ogino S, Fukui H. Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale. Methods Find Exp Clin Pharmacol. 2008 Apr. 30(3):225-30. [Medline].
Hishinuma S, Sato Y, Kobayashi Y, Komazaki H, Saito M. Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008 May. 107(1):66-79. [Medline].
Obradovic T, Dobson GG, Shingaki T, Kungu T, Hidalgo IJ. Assessment of the first and second generation antihistamines brain penetration and role of P-glycoprotein. Pharm Res. 2007 Feb. 24(2):318-27. [Medline].
de Leon J, Nikoloff DM. Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports. CNS Spectr. 2008 Feb. 13(2):133-5. [Medline].
Lucero ML, Arteche JK, Sommer EW, Casadesus A. Preclinical toxicity profile of oral bilastine. Drug Chem Toxicol. 2012 Jun. 35 Suppl 1:25-33. [Medline].
Bektas F, Eken C, Oktay C. Pseudoephedrine-induced paroxysmal supraventricular tachycardia: a case report. J Emerg Med. 2010 Jun. 38(5):e53-7. [Medline].
Bilici M, Turkay S, Yilmaz AE, Kurtaran H, Catal F, Tonbul A, et al. Effect of pseudoephedrine on cardiac rhythm of children with rhinitis. Indian J Pediatr. 2011 Nov. 78(11):1361-4. [Medline].
American Hospital Association (AHA) Annual Survey Database,. Fiscal Year 2003. Health Forum LLC,. One North Franklin Street, Chicago, IL 60606: Copyright 2003, .
Bryner JK, Wang UK, Hui JW, Bedodo M, MacDougall C, Anderson IB. Dextromethorphan abuse in adolescence: an increasing trend: 1999-2004. Arch Pediatr Adolesc Med. 2006 Dec. 160(12):1217-22. [Medline]. [Full Text].
Flynn CA, Griffin GH, Schultz JK. WITHDRAWN: Decongestants and antihistamines for acute otitis media in children. Cochrane Database Syst Rev. 2007 Jul 18. CD001727. [Medline].
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015 Dec. 53 (10):962-1147. [Medline].
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Dart RC. 2010 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th Annual Report. Clin Toxicol (Phila). 2011 Dec. 49(10):910-41. [Medline]. [Full Text].
Sen A, Akin A, Craft KJ, Canfield DV, Chaturvedi AK. First-generation H1 antihistamines found in pilot fatalities of civil aviation accidents, 1990-2005. Aviat Space Environ Med. 2007 May. 78(5):514-22. [Medline].
Guide for Aviation Medical Examiners: Pharmaceuticals (Therapeutic Medications) Allergy-Antihistimines. Federal Aviation Administration; October 24, 2012. 207. Available at http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/.
Kamijo Y, Soma K, Sato C, Kurihara K. Fatal diphenhydramine poisoning with increased vascular permeability including late pulmonary congestion refractory to percutaneous cardiovascular support. Clin Toxicol (Phila). 2008 Nov. 46(9):864-8. [Medline].
Matsunaga C, Izumi S, Furukubo T, Satoh M, Yamakawa T, Uchida T, et al. Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy. Clin Nephrol. 2007 Aug. 68(2):93-8. [Medline].
Karpa KD, Felix TM, Lewis PR. Adverse Effects of Common Drugs: Children and Adolescents. FP Essent. 2015 Sep. 436:17-22. [Medline].
Yang M, So TY. Revisiting the safety of over-the-counter cough and cold medications in the pediatric population. Clin Pediatr (Phila). 2014 Apr. 53 (4):326-30. [Medline].
Birring SS, Kavanagh J, Lai K, Chang AB. Adult and paediatric cough guidelines: Ready for an overhaul?. Pulm Pharmacol Ther. 2015 Feb 11. [Medline].
Tashiro M, Sakurada Y, Mochizuki H, Horikawa E, Maruyama M, Okamura N, et al. Effects of a sedative antihistamine, D-chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving. Hum Psychopharmacol. 2008 Mar. 23(2):139-50. [Medline].
Bebarta VS, Blair HW, Morgan DL, Maddry J, Borys DJ. Validation of the American Association of Poison Control Centers out of hospital guideline for pediatric diphenhydramine ingestions. Clin Toxicol (Phila). 2010 Jul. 48(6):559-62. [Medline].
Tobin JR, Doyle TP, Ackerman AD, Brenner JI. Astemizole-induced cardiac conduction disturbances in a child. JAMA. 1991 Nov 20. 266(19):2737-40. [Medline].
Nine JS, Rund CR. Fatality from diphenhydramine monointoxication: a case report and review of the infant, pediatric, and adult literature. Am J Forensic Med Pathol. 2006 Mar. 27(1):36-41. [Medline].
Mendoza FS, Atiba JO, Krensky AM, Scannell LM. Rhabdomyolysis complicating doxylamine overdose. Clin Pediatr (Phila). 1987 Nov. 26(11):595-7. [Medline].
Cravo M, Gonçalo M, Figueiredo A. Fixed drug eruption to cetirizine with positive lesional patch tests to the three piperazine derivatives. Int J Dermatol. 2007 Jul. 46(7):760-2. [Medline].
Köppel C, Ibe K, Tenczer J. Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. J Toxicol Clin Toxicol. 1987. 25(1-2):53-70. [Medline].
Feldman MD, Behar M. A case of massive diphenhydramine abuse and withdrawal from use of the drug. JAMA. 1986 Jun 13. 255(22):3119-20. [Medline].
Gupta SK, Kantesaria B, Wang Z. Multiple-dose pharmacokinetics and safety of desloratadine in subjects with moderate hepatic impairment. J Clin Pharmacol. 2007 Oct. 47(10):1283-91. [Medline].
Frascogna N. Physostigmine: is there a role for this antidote in pediatric poisonings?. Curr Opin Pediatr. 2007 Apr. 19(2):201-5. [Medline].
[Guideline] Pediatric basic and advanced life support. 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation. 2005 Nov 29. 112(22 Suppl); III73-90.
Haase U, Rundshagen I. [Pharmacotherapy--physostigmine administered post-operatively]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2007 Mar. 42(3):188-9. [Medline].
Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A. Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study. Eur J Clin Pharmacol. 2007 Nov. 63(11):1011-7. [Medline].
Janssens F, Leenaerts J, Diels G, De Boeck B, Megens A, Langlois X, et al. Norpiperidine imidazoazepines as a new class of potent, selective, and nonsedative H1 antihistamines. J Med Chem. 2005 Mar 24. 48(6):2154-66. [Medline].
Kabat-Koperska J, Safranow K, Golembiewska E, Domanski L, Ciechanowski K. Creatinine clearance after cimetidine administration: is it useful in the monitoring of the function of transplanted kidney?. Ren Fail. 2007. 29(6):667-72. [Medline].
Lassaletta A, Martino R, Gónzalez-Santiago P, Torrijos C, Cebrero M, García-Frías E. Reversal of an antihistamine-induced coma with flumazenil. Pediatr Emerg Care. 2004 May. 20(5):319-20. [Medline].
[Guideline] Scharman EJ, Erdman AR, Wax PM, Chyka PA, Caravati EM, Nelson LS, et al. Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006. 44(3):205-23. [Medline].
Serio RN. Acute delirium associated with combined diphenhydramine and linezolid use. Ann Pharmacother. 2004 Jan. 38(1):62-5. [Medline].
Simons FE. Safety of levocetirizine treatment in young atopic children: An 18-month study. Pediatr Allergy Immunol. 2007 Sep. 18(6):535-42. [Medline].
Stojanovski SD, Baker SD, Casavant MJ, Hayes JR, Robinson RF, Nahata MC. Implications of diphenhydramine single-dose unintended ingestions in young children. Pediatr Emerg Care. 2007 Jul. 23(7):465-8. [Medline].
Sype JW, Khan IA. Prolonged QT interval with markedly abnormal ventricular repolarization in diphenhydramine overdose. Int J Cardiol. 2005 Mar 18. 99(2):333-5. [Medline].
Thakur AC, Aslam AK, Aslam AF, Vasavada BC, Sacchi TJ, Khan IA. QT interval prolongation in diphenhydramine toxicity. Int J Cardiol. 2005 Feb 15. 98(2):341-3. [Medline].
Yamaura K, Shigemori A, Suwa E, Ueno K. Expression of the histamine H4 receptor in dermal and articular tissues. Life Sci. 2013 Feb 7. 92(2):108-13. [Medline].