Pharmacists can educate patients on preventive measures to avoid heat-related illnesses.
The hottest temperature ever recorded on Earth was 130oF in Death Valley National Park, and the US is careening toward that record this summer.1 The last thing anyone wants is to make it even worse, but hypersensitivity to heat may be associated with some medications.2-7 Below are 10 common medication classes that could be increasing a patient’s heat intolerance.
Synthesized in 1959 and released in 1962, the loop diuretic furosemide (Lasix; Sanofi) has been a key component in heart failure, hypertension, and edema management for well over 6 decades.8 It acts on the Loop of Henle and inhibits sodium and chloride reabsorption in the ascending Loop of Henle as well as the proximal and distal renal tubules, leading to fluid and electrolyte excretion such as sodium, chloride, magnesium, calcium, and potassium.9,10
Similarly, hydrochlorothiazide (HCTZ), a thiazide diuretic, has been around for nearly 6 decades as well, helping patients with edema, volume overload, and chronic hypertension.11 Compared with furosemide, HCTZ acts in the distal convoluted tubule, inhibiting sodium reabsorption and promoting sodium, water, and potassium excretion.10
Diuretics’ ability to cause electrolyte imbalances and volume depletion (due to pulling salt and fluid from the kidneys into the urine) leads to hypovolemia, dehydration, and frequent urination, causing intolerance to heat.2,3-5,7
Commonly used in chronic angina, β blockers such as atenolol (Tenormin; Almatica Pharma), metoprolol (Lopressor; Validus Pharmaceuticals), and propranolol (Inderal; ANI Pharmaceuticals, Inc) can cause heat intolerance by reducing the superficial vasodilation of the blood vessels, which helps cool the skin.12,13 It may seem counterintuitive, but the β adrenergic receptor located in the heart helps circulate blood to cool. Slower heart rate and reduced blood pressure will cause decreased sweating, which will lead to disruption in the body’s natural temperature control and a higher risk of masking heat-related symptoms, such as dehydration and dizziness.2,5,7
Although multiple sources say antiplatelet agents in general cause heat insensitivity, clopidogrel (Plavix; Bristol-Myers Squib, Sanofi) is specifically notable for its ability to reduce peripheral vasodilation, or the blood’s ability to cool the skin.2,4,5,14 By blocking the P2Y12 component of adenosine diphosphate receptors, it prevents activation of the glycoprotein IIb/IIIa receptor but also reduces protein kinase phosphorylation of vasodilator-stimulated phosphoprotein, which leads to decreased peripheral vasodilation.14-16 One study’s findings suggested clopidogrel may alter central hypothalamic thermoregulatory control even with minimal blood brain barrier crossing.14
Lisinopril (Zestril; Twi Pharmaceuticals) is used for acute coronary syndrome (ACS), heart failure with reduced ejection fraction (HFrEF), and most commonly in the treatment of hypertension.17 It is a competitive inhibitor of angiotensin-converting enzyme that prevents the conversion of angiotensin I to angiotensin II.18
Valsartan (Diovan; Novartis) and losartan (Cozaar; Organon) are used for ACS, HFrEF, and hypertension, as well. They block the nonpeptide angiotensin II receptor competitively and selectively, leading to vasodilation, natriuresis, and decreased blood pressure.19
ACEi and ARBs affect angiotensin, a potent vasodilator that decreases blood pressure, which affects the body’s core ability to cool itself, but angiotensin itself also affects thirst. Angiotensin II has a widespread effect on thirst and sodium appetite, and inhibition can reverse the usual increase in water intake, decreasing the appetite for water.2,3-5,19,20
Haloperidol (Haldol; Essential Pharma), introduced in October of 1959, was a breakthrough drug for patients with schizophrenia. It works by acting on the postsynaptic dopaminergic D2 receptors in the brain.21 Olanzapine (Zyprexa; Eli Lilly) acts as a potent antagonist for serotonin 5-HT2A, muscarinic, and dopaminergic receptors.22 Finally, quetiapine (Seroquel; Cheplapharm) acts as an antagonist on the dopamine and serotonin receptors, much like olanzapine but without the effects on muscarinic receptors.23
Haloperidol is known for its potential to cause neuroleptic malignant syndrome (NMS) and its mechanism causes dysregulation of temperature within the body. Similarly, olanzapine and quetiapine can cause NMS and heat intolerance due to the blockage of dopaminergic receptors, causing dysregulation of temperature.2-5,7,24
Sertraline (Zoloft; Viatris) and fluoxetine (Prozac; Eli Lilly) both act on the presynaptic serotonin, inhibiting its reuptake.25 Serotonin inhibition affects the hypothalamus, which is responsible for sweating and cooling the body.2,26 SSRIs are also related to reduced alertness, judgement, and perception of hot weather due to potential cognitive impairments.2-4,26 Sertraline and fluoxetine are commonly associated with hyponatremia due to an increase in serotonin activating syndrome of inappropriate antidiuretic hormone secretion (SIADH), causing excessive water retention and electrolyte imbalance.27,28
As their name suggests, duloxetine (Cymbalta; Eli Lilly) and venlafaxine (Effexor; Viatris, Pfizer) both inhibit the reuptake of serotonin and norepinephrine.25 SNRIs are like SSRIs in the way they inhibit serotonin, and they also cause the hypothalamus to impair the body’s ability to self-regulate.2-4,26 Venlafaxine can also lead to hyponatremia.29
Amitriptyline, the second tricyclic antidepressant to be marketed for major depressive disorder in 1961, acts in the central nervous system by inhibiting the reuptake of serotonin and norepinephrine in the presynaptic neuronal membrane pump, allowing for increased concentration.30 Its effects on serotonin, much like its sister classes SSRIs and SNRIs, causes decreased sweating from impairments occurring in the hypothalamus. Amitriptyline also has a strong anticholinergic effect, causing alterations in central thermoregulation, blurry vision, and increasing risk of fainting and falls.2-5,7
When discussing heat tolerance, diphenhydramine (Benadryl; Kenvue) is most likely be the first medication noted due to its antihistamine and anticholinergic properties. Its mechanism of action directly competes with histamine on effector cells and also possesses anticholinergic and sedative effects.31 Although it is true that anticholinergic medications have famously been linked to feeling hot, dry, and confused, studies have shown that at typical OTC doses, diphenhydramine does not cause an increase in temperature for healthy adults.32,33 However, in older adults and those with chronic conditions, the anticholinergic properties can impair sweat production; cause dry mouth, nose, and throat; and alter central thermoregulation.2-5
Methylphenidate (Ritalin; Novartis) blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and stimulates the central nervous system.34 By increasing the metabolic rate of the body and amplifying the heart rate and respiration rate via autonomic sympathetic response, stimulants can disrupt the body’s cooling mechanisms, causing inability to cool down.2,4,5,7 However, study findings have shown that stimulant medications, including methylphenidate, led to a decreased risk of heat-related illnesses such as dehydration, hyperthermia, and heat stroke.35 More research is warranted on this topic to clarify the effects of stimulants on heat tolerance.
Liang Jun Ren is a 2027 PharmD candidate at Saint Joseph’s University in Philadelphia.
Thomas F. Turco, PharmD, is pharmacy team leader at the Hospital of the University of Pennsylvania–Cedar Avenue in Philadelphia.
The authors have no financial disclosures and no relationship with any pharmaceutical company whose products are mentioned in this article or with the manufacturers of competing products.
Pharmacists are often the first and most frequent source of medication counseling and education. Pharmacists should advise patients to not stop taking their medications because of the potential for heat intolerance and to store their medications in a dry, cool area to avoid drug destabilization.6,36 Remind patients with travel plans to check the weather for their destination and bring appropriate prevention measures, such as water and sunscreen, and take preventative actions such as seeking shade and taking frequent breaks to avoid heat sickness.6,36
Recommendations from the American Academy of Family Physicians include gradually increasing exercise intensity and duration over a period of 1 to 2 weeks in order to acclimate to a new climate.6 Other recommendations include limiting strenuous activities during peak temperatures; limiting travel during hot and humid seasons; remaining hydrated; wearing light-colored, loose-fitting clothing; and learning about symptoms of heat stroke and dehydration, such as dizziness, thirst, heavy sweating, nausea, confusion, and weakness.6 Pharmacists should be aware that the patients at highest risk are older adults and individuals with chronic conditions, increased body mass index, sedentary or deconditioned lifestyles, or a history of heat-related illnesses.6 Education about proper medication usage, prevention measures, and symptoms of heat-related illness will help patients beat the heat.
