Thermoregulatory considerations and research gaps involving the use of commonly prescribed medications

DrugPhysiologic OutcomesClinical ConsiderationResearch Gaps
MetforminGut-related changes1) Drug initiation should be conservative and progressive
2) Continually review drug tolerance and adjust doses
1) Profile short- and long-term metformin-associated gut flora changes
2) Profile biomarkers of endotoxemia and inflammation during heat stress in patients receiving metformin
SGLT2 inhibitorsOsmotic diuresis (AKI/CKD risk)1) Drug-associated diuresis may increase AKI risk
2) Monitor and report symptoms such as diuresis, postural hypotension, and excessive dizziness
3) Hydration status of susceptible patients with:
a) Concomitant diuretic medication
b) Congestive heart failure
c) Prolonged heat exposure
1) Large-scale prospective studies monitoring renal injury and heat-related hospitalisations with SGLT2 inhibitor use in patients frequently exposed to prolonged exertional heat stress
InsulinMetabolic heat production1) Insulin may raise metabolic heat production and may contribute to greater heat storage, especially in extreme heat
2) Patients should be monitored for hyperthermic responses and appropriate cooling strategies may be required, especially during exertion in the heat
1) Determine the extent of thermoeffector response to heat stress at varying insulin and glycemic levels of patients to isolate insulinemic and glycemic effects on thermoregulation
AntiplateletsThermoeffector response1) Caution advised for patients taking antiplatelet medications before exercise or work in extreme heat1) Determine influence of COX inhibition by aspirin on central control of body temperature
2) Influence of antiplatelet medication on vasomotor adaptations to heat acclimation programs
ACEI and ARBRenal changes (AKI/CKD risk)1) Hydration status of susceptible patients with:
 a) Concomittant diuretic medication
 b) Congestive heart failure
 c) Prolonged heat exposure
1) Assess the effects of ACEIs/ARBs on thirst responses in aging patients
2) Determine efficacy of fluid replenishment strategies in patients on ACEIs/ARBs
Exercise tolerance1) Determine ACEI/ARBs’ effects on exercise tolerance during exertional heat stress
Thermoeffector response1) Determine influence of ACEIs/ARBs on sweat and skin blood flow responses
β-blockersThermoeffector response1) Medication effects on thermoeffector responses:
 a) Inhibited cutaneous vasodilation
 b) Potentiated sweat response
 c) Effects of selective versus nonselective β-blockers
1) Elucidate cardiovascular mechanisms underpinning suppressed SkBF during heat stress
2) Determine effects of selective and nonselective β-blockers on sweat responses across populations in different levels of heat stress
3) Elucidate the impacts of β3 receptor activation and inhibition in BAT activated thermogenesis during heat stress
Anticholinergics and cholinesterase inhibitorsThermoeffector response1) Medication effects on thermoeffector responses:
a) Inhibited sweat response
b) Increased rate of rise in body core temperature
1) Dose-response studies to identify the “dose threshold” at which thermoregulatory responses will be altered by ACh-modulating medications
Dopamine replacement agents and dopamine agonistsThermoeffector response1) Potential thermoregulatory dangers of dose adjustments and withdrawal1) Influence of L-dopa on overall thermal perception in older PD patients under resting conditions
Perceptual1) “Dampening” effect of medication on thermal sensation and perceived exertion during exercise
Chemotherapy (e.g., platinum analogs, taxanes, bortezomib)CIPN1) Hyperthermia may occur secondary to chemotherapy-induced anhidrosis1) Health impacts of extreme or prolonged heat exposures in cancer patients
2) Health impacts of chemotherapy medications during extreme or prolonged heat exposures
3) Efficacy of exercise programs to mitigate chemotherapy-induced thermoregulatory perturbations
Early menopause (Hot flushes)1) Chemotherapy-induced early menopause risk associated with age
2) HRTs not recommended in hormone-dependent cancers (e.g., breast cancer) to treat hot flush
3) Alternative hot flush treatments:
a) Paroxetine
b) Fluoxetine
c) Venlafaxine
d) Citalopram
  • Abbreviations: ACEI, angiotensinogen converting enzyme inhibitor; ACh, acetylcholine; AKI, acute kidney injury; ARB, angiotensin receptor blocker; BAT, brown adipose tissue; CIPN, chemotherapy-induced peripheral neuropathy; CKD, chronic kidney disease; COX, cyclooxygenase; HRT, hormone replacement therapy; PD, Parkinson’s disease; SGLT2, sodium-glucose cotransporter 2; SkBF, skin blood flow.