Sedating or ass hole

Nonprescription antihistamines are approved by FDA for temporary relief of allergic rhinitis symptoms.1 Diphenhydramine is also an FDA-approved antitussive, nighttime sleep aid, and antiemetic.1 In addition, nonprescription antihistamines are often self-selected for management of common cold symptoms.

H1 antihistamines are commonly classified by functional class (e.g., first generation [sedating] and second generation [nonsedating]). With similar efficacy, adverse effects depend on the ability of the H1 antihistamines to block muscarinic, adrenergic, and serotonergic receptors and to cross the blood–brain barrier.2 The first-generation nonprescription H1 antihistamines (i.e., brompheniramine, chlorpheniramine, clemastine, dexbrompheniramine, diphenhydramine) cross the blood–brain barrier and are associated with central nervous system adverse effects (e.g., drowsiness, fatigue, dizziness, impaired thinking and memory, agitation, and hallucinations; children and the elderly may experience paradoxical excitation and agitation). With the exception of cetirizine, sedation is not a noteworthy issue with usual doses of the second-generation nonprescription H1 antihistamines (i.e., cetirizine, fexofenadine, loratadine). Anticholinergic adverse effects associated with the first-generation H1 antihistamines include dry mouth, dry eyes, pupillary dilatation, urinary retention, constipation, memory defects, dizziness, postural hypotension, and weight gain. Some first-generation H1 antihistamines block alpha-adrenergic receptors, serotonin receptors, and cardiac ion currents, contributing to cardiovascular toxicities such as dysrhythmias, prolongation of the QT interval, and postural hypotension.3

Physiologic changes associated with aging may increase the risk of medication-related adverse effects. Comorbidities may increase the number of medications taken by the elderly, increasing the risk for drug–disease and drug–drug interactions. Mental status changes and fall risk are of special concern for adults 65 years or older. The U.S. Census Bureau predicts that adults 65 years or older will represent 19.6% of the population by 2030,4 suggesting that the number of older adults taking inappropriate medications may markedly increase as the U.S. population ages. First-generation H1 antihistamines with anticholinergic adverse effects are of great concern.

The American Geriatrics Society (AGS) updated Beers list of potentially inappropriate medications in older adults includes five nonprescription first-generation H1 antihistamines (brompheniramine, chlorpheniramine, clemastine, dexbrompheniramine, and diphenhydramine [oral]) and seven prescription first-generation H1 antihistamines (carbinoxamine, cyproheptadine, dexchlorpheniramine, doxylamine, hydroxyzine, promethazine, and triprolidine).5 Despite the availability of the Beers criteria for more than 2 decades, first-generation H1 antihistamines continue to be prescribed for and self-selected by adults 65 years or older. In a 1999 national sample of prescription drug claims in individuals 65 years or older, 13.6% filled prescriptions for a first-generation H1 antihistamine (hydroxyzine, 6.9%; promethazine, 6.7%).6 Among adults 65 years or older, 4.2% of women and 3.9% of men reported taking diphenhydramine.7 Diphenhydramine was the 19th most commonly reported medication reported by women 65 years or older and the 21st most commonly reported medication by men 65 years or older.7

Patients, pharmacists, and other health professionals need to be aware of the potential dangers associated with first-generation H1 antihistamines and follow the AGS recommendation that these medications should not be taken by adults 65 years or older.5


  1. Food and Drug Administration. CFR: Code of Federal Regulations Title 21. Accessed at, August 6, 2012.
  2. Brunton LL, Chabner BA, Knollman BC (Eds.). Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011.
  3. Simons FER. Advances in H1 antihistamines. New Engl J Med. 2004;351:2203–17.
  4. Census Bureau 2004 U.S. interim projections by age, sex, race, and Hispanic origin. Accessed at…, July 30, 2012.
  5. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616–31.
  6. Curtis LH, Østbye T, Sendersky V, et al. Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med. 2004;164:1621–5.
  7. Slone Survey. Patterns of medication use in the United States: 2006. Accessed at, August 1, 2012.