Do common over-the-counter antihistamine medications modify thermoregulatory responses during passive heat stress?

Abstract

Over the coming decade, climate change is expected to increase the duration and intensity of pollen season and contribute to higher atmospheric concentrations of inhaled allergens (Corden & Millington, 2001; D’Amato et al, 2015). This is likely to increase the number of individuals who suffer from respiratory conditions such as allergic rhinitis (AR), worsen their symptoms, and stress healthcare infrastructure (Beggs, 2004; Kim et al, 2018; Ziska & Caulfield, 2000; Ziska et al, 2019). Currently, guidance suggests all antihistamines may increase an individuals’ risk of heat-related illness/injury (HRI) during heat stress by suppressing human thermoeffector responses (Casa et al, 2015; Coco et al, 2016; OSHA, 2011; O’Connor & DeGroot, 2024; Roberts et al, 2023; WHO, 2011). However, whether over-the-counter (OTC) antihistamines for allergy, taken as recommended, alter sudomotor and/or cardiovascular responses during heat stress has not been critically analyzed in humans. This thesis sought to determine whether the oral ingestion of three common OTC antihistamines (diphenhydramine, loratadine & desloratadine) would alter sudomotor, cardiovascular, or perceptual responses to heat stress when compared to a placebo pill (sugar). A total of 10 young healthy participants (5M, 5F, 22.6 ± 1.8 yrs, 174 ± 10 cm, 73.6 ± 10.8 kg) completed our double-blind randomized crossover procedure where they consumed either i) 50 mg diphenhydramine ii) 10 mg loratadine iii) 5 mg desloratadine or iv) a sugar pill before being passively heated to a mean body temperature 1.5℃ above baseline. Preliminary data suggests that OTC antihistamines do not alter local sweat rate of the forearm [Mg/cm2/min1 (Placebo (PLA): 0.411, diphenhydramine (DPH): 0.436, loratadine (LOR): 0.368, desloratadine (DES): 0.432)], skin blood flow [%max (DPH: 25.71, LOR: 21.81, DES: 21.10, PLA: 21.27)], heart rate [BPM (DPH: 72.25, LOR: 78.34, DES: 74.86, PLA: 74.94)], mean arterial pressure [Mm/Hg (DPH: 81.95, LOR: 82.09, DES: 82.20, PLA: 80.98)], or rate-pressure product [Mm/Hg (DPH: 8604, LOR: 9051, DES: 9126, PLA: 8851)] during passive heating, suggesting they may continue to be a safe option to allergic symptom management during periods of heat exposure. Further research aimed at examining different OTC antihistamines and/or doses, in other heat-vulnerable groups and types of heat stress is required to wholly conclude the HRI risk posed by OTC antihistamines.