Alabama Anesthesia Professionals

Diphenhydramine for Sedation

Diphenhydramine, a first-generation antihistamine, is known for its effectiveness in treating allergic reactions and its potent sedative properties (1). Discovered in the 1940s, it has become a staple in clinical and over-the-counter settings (2). Diphenhydramine directly impacts the central nervous system by crossing the blood-brain barrier, which allows it to influence the brain’s histamine pathways directly to generate relaxation and sedation (3). This ability makes it valuable for various medical uses, including pre-anesthetic medication and treatment for acute allergic reactions (4). However, when used as allergy medicine, it must be dosed carefully due to its sedative effects (5).

Diphenhydramine’s sedative effects are enhanced by its impact on neurotransmitter systems in addition to the histamine pathway (1). It exhibits significant anticholinergic activity by blocking muscarinic receptors and reducing central nervous system activity, contributing to its effectiveness in treating motion sickness and enhancing its sedative quality (11). However, this broad receptor activity also accounts for various anticholinergic side effects, such as dry mouth, blurred vision, and urinary retention, which can significantly complicate its use in the at-risk population (10).

Although it is not considered a true anesthetic, diphenhydramine can induce sedation and aid in the induction of relaxation and preparation for anesthesia (9). It can be employed across a range of clinical settings and is commonly administered to ease patient anxiety and boost the effectiveness of painkillers and other sedatives before surgical procedures. When it comes to sleep disorders, diphenhydramine is a critical ingredient in many over-the-counter sleep aids (12). This has made it a popular choice for individuals who have occasional insomnia. However, it is generally not recommended for long-term use in chronic sleep disturbances because of the risk of developing tolerance and dependence (12).

Despite its benefits, using diphenhydramine for sedation must be carefully managed due to the risk of cognitive and psychomotor impairment (5). These effects can profoundly impact an individual’s ability to perform tasks requiring mental alertness, such as driving or operating machinery. The risk is particularly pronounced in older populations, who are more susceptible to falls, decreased reaction times, and other injuries because of sedation (6). Furthermore, paradoxical excitation, a less common but notable side effect, can occur, particularly in children and geriatric populations, manifesting as increased restlessness and agitation rather than the intended sedation (7). It is important to note that severe anticholinergic symptoms, CNS depression, and, in rare cases, fatal outcomes can also occur (8). Medical professionals should educate and raise awareness among users about the safety and appropriate use of diphenhydramine, particularly when used for self-medication.

While diphenhydramine remains a valuable tool for sedation due to its efficacy and multiple mechanisms of action, its use requires careful consideration of the balance between therapeutic benefits and potential risks. Widespread availability can lead to its misuse and possible overdose, resulting in severe consequences. Continuous education for healthcare professionals and patients on the appropriate utilization, diligent monitoring for adverse effects, and cautious administration in high-risk populations are essential in maximizing diphenhydramine’s efficacy while minimizing potential harm.

References

  1. National Center for Biotechnology Information. (2024). PubChem compound summary for CID 3100, Diphenhydramine. Retrieved June 11, 2024, from https://pubchem.ncbi.nlm.nih.gov/compound/Diphenhydramine
  2. Fein, M. N., Fischer, D. A., & O’Keefe, A. W. et al. (2019). CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy, Asthma & Clinical Immunology, 15, 61. https://doi.org/10.1186/s13223-019-0375-9
  3. Sicari, V., & Zabbo, C. P. (2023). Diphenhydramine. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK526010/
  4. Alhwimani, A. K., Aljohani, R. A., & Altulaihi, B. A. (2021). The use of over-the-counter sleep aid containing diphenhydramine hydrochloride among Saudis. Cureus, 13(12), e20622. https://doi.org/10.7759/cureus.20622
  5. Agostini, J. V., Leo-Summers, L. S., & Inouye, S. K. (2001). Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Archives of Internal Medicine, 161(17), 2091-2097. https://doi.org/10.1001/archinte.161.17.2091
  6. Abraham, O., Schleiden, L., & Albert, S. M. (2017). Over-the-counter medications containing diphenhydramine and doxylamine used by older adults to improve sleep. International Journal of Clinical Pharmacy, 39(4), 808-817. https://doi.org/10.1007/s11096-017-0467-x
  7. de Leon, J., & Nikoloff, D. M. (2008). Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: Three case reports. CNS Spectrums, 13(2), 133-135. https://doi.org/10.1017/s109285290001628x
  8. Huynh, D. A., Abbas, M., & Dabaja, A. (2023). Diphenhydramine toxicity. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557578/
  9. Pavlidakey, P. G., Brodell, E. E., & Helms, S. E. (2009). Diphenhydramine as an alternative local anesthetic agent. The Journal of Clinical and Aesthetic Dermatology, 2(10), 37-40.
  10. López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019). Anticholinergic drugs in geriatric psychopharmacology. Frontiers in Neuroscience, 13, 1309. https://doi.org/10.3389/fnins.2019.01309
  11. Schaefer, T. S., Patel, P., & Zito, P. M. (2024). Antiemetic histamine H1 receptor blockers. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK533003/
  12. Pagel, J. F., & Parnes, B. L. (2001). Medications for the treatment of sleep disorders: An overview. Primary Care Companion to the Journal of Clinical Psychiatry, 3(3), 118-125. https://doi.org/10.4088/pcc.v03n0303