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Title: Over-the-counter drugs and non-febrile thermoregulation : is there cause for concern?
Author: Foster, Josh
ISNI:       0000 0004 7226 7513
Awarding Body: University of Bedfordshire
Current Institution: University of Bedfordshire
Date of Award: 2017
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Core temperature (Tc) regulation is fundamental to mammalian survival, since hypothermia (Tc ≤ 35°C) and hyperthermia (Tc ≥ 40°C) are major risk factors for health and wellbeing. The purpose of this thesis was to determine if acetaminophen, an analgesic and antipyretic drug, increased the onset of hypothermia or hyperthermia during passive cold and heat stress, respectively. It was later investigated if acetaminophen induced inhibition of cyclooxygenase mediated these side-effects. In Study 1a, the plasma acetaminophen response to a dose of 20 mg·kg-1 of lean body mass was determined through enzyme linked immunosorbent assay. In Study 1b, the effect of acetaminophen administration on internal temperature (rectal; Tre) during a passive 2-hour mild cold (20°C, 40% relative humidity) exposure was examined. Study 1a showed that the plasma response was homogenous between subjects, reaching peak concentrations between 80-100 minutes (14 ± 4 μg·ml-1). In Study 1b, acetaminophen reduced Tre in all participants compared with baseline, and the average peak reduction was 0.19 ± 0.09°C. In contrast, Tre remained stable when participants ingested a sugar placebo. Study 1 is the first experiment which confirms a hypothermic side-effect of acetaminophen in healthy humans. Study 2 investigated whether acetaminophen augmented the rate of Tre rise during exposure to passive dry (45°C, 30% r.h.) and humid (45°C, 70% r.h.) heat stress for 2-hours and 45-minutes, respectively. This study showed that the rate of Tre rise in the dry (0.005 vs 0.006°C∙min-1) and humid (0.023 vs 0.021 °C∙min-1) conditions were similar between the acetaminophen and placebo trials (p > 0.05). Study 2 is the first experiment which confirms acetaminophen has no meaningful effect on thermoregulation during passive dry or humid heat exposure. Study 3 determined how the hypothermic effect of acetaminophen changes during exposure to a thermoneutral (25°C, 40% r.h.) and cold (10°C, 40% r.h.) environment for 2-hours. In summary, there was no hypothermic effect of acetaminophen in a thermoneutral environment (p > 0.05), whereas Tre fell by 0.40 ± 0.15°C compared with baseline during cold stress (p < 0.05). Compared with the placebo, Tre was ~0.35°C lower at 120 minutes, but was significantly lower from 70-minutes. Study 3 confirmed that there is a relationship between the level of cold stress and magnitude of the hypothermic effect of acetaminophen. Study 4 determined whether ibuprofen (400 mg), a cyclooxygenase inhibitor, reduced Tre during 2-hour passive cold stress (10°C, 40% r.h.) to a level comparable with acetaminophen. Ibuprofen administration did not influence Tre, vastus medialis shivering, or energy expenditure compared with a placebo throughout the cold exposure (p > 0.05). Taken together, this renders it unlikely that cyclooxygenase activity is required for thermogenesis induced by skin cooling. Study 4 provides evidence that acetaminophen induced hypothermia is not exclusively mediated by cyclooxygenase inhibition. In Summary, this series of experiments has shown that acetaminophen has a hypothermic side effect in healthy humans, which is amplified during acute cold stress. Ibuprofen had no such effect on thermoregulation during cold exposure, so it is unlikely that cyclooxygenase inhibition mediates the hypothermic side-effect of acetaminophen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: paracetemol ; hypothermia ; hyperthermia ; body temperature ; ibuprofen