Antihistamines are among the most frequently used medications globally. They function by blocking the effects of histamine, a chemical released during an allergic reaction. While generally considered safe, these common allergy drugs can sometimes cause heart palpitations—a noticeable change in heartbeat. These sensations may feel like a fluttering, pounding, racing, or skipping of the heart. Understanding the biological differences between these medications explains why some can cause this side effect.
Classification of Antihistamines and Cardiac Risk
Antihistamines are separated into first-generation and second-generation agents, a distinction that directly affects their potential to impact the heart. Older, first-generation drugs, such as diphenhydramine and hydroxyzine, carry a higher risk of cardiac side effects. This risk stems from their structural properties, which allow them to interact non-selectively with various receptors throughout the body, not just histamine receptors.
First-generation antihistamines are highly lipophilic, meaning they easily cross the blood-brain barrier and the membranes of heart cells. This broad interaction leads to side effects like sedation and cardiovascular issues. In contrast, second-generation antihistamines, such as loratadine and fexofenadine, are more selective for peripheral histamine receptors. They are less lipophilic and do not readily penetrate the central nervous system or the heart muscle, making them safer regarding cardiac complications.
The most significant cardiac safety concerns were initially raised by older second-generation drugs, namely terfenadine and astemizole, which have since been withdrawn from the market. These compounds posed a risk, especially when their metabolism was impaired. Newer second-generation drugs demonstrate a higher safety profile because they do not exhibit the same harmful interactions with the heart’s electrical system as their predecessors.
The Mechanism: Drug Interaction with Heart Rhythm
The scientific explanation for how certain antihistamines trigger palpitations lies in their interference with the heart’s precise electrical timing. The heart’s rhythm is maintained by electrical impulses regulated by the flow of ions, such as potassium and sodium, through channels in the heart muscle cell membranes. A component of this process is the repolarization phase, where the heart muscle cells reset their electrical charge to prepare for the next beat.
This repolarization process is largely controlled by a specific protein channel known as the hERG (human Ether-à-go-go-Related Gene) potassium channel. The hERG channel mediates the rapid delayed rectifier potassium current, which is essential for terminating the electrical impulse. Certain antihistamines, particularly the older first-generation types, possess a molecular structure that allows them to physically block or inhibit the normal function of this hERG channel. When the channel is blocked, the outflow of potassium ions is reduced, causing the electrical resetting phase to be prolonged.
On an electrocardiogram (ECG), this delay in repolarization is represented by a lengthening of the QT interval. This condition, known as QT prolongation, destabilizes the heart’s electrical system, creating an environment where abnormal, rapid, and disorganized heartbeats can spontaneously arise. The resulting electrical instability can manifest as the sensation of heart palpitations or, in more severe and rare instances, as a life-threatening ventricular arrhythmia called Torsades de Pointes. The core mechanism is the drug’s physical binding to and blocking of the hERG potassium channel, directly disrupting the heart’s natural rhythm.
Factors That Increase the Risk of Palpitations
Several external and internal factors can heighten the chance of a person experiencing cardiac side effects from antihistamines.
Drug Interactions
Drug interactions are a primary concern, especially those involving medications that inhibit the liver enzymes responsible for breaking down the antihistamine. Taking a first-generation antihistamine alongside certain macrolide antibiotics (like erythromycin) or antifungal agents (such as ketoconazole) can interfere with the CYP3A4 enzyme system. This interference leads to a buildup of the antihistamine in the bloodstream, driving its concentration to toxic levels that increase hERG channel blockage.
Underlying Health Conditions
Underlying health conditions modify an individual’s susceptibility to drug-induced cardiac issues. People with pre-existing heart disease, inherited Long QT syndrome, or structural heart abnormalities are more vulnerable to rhythm disturbances. Imbalances in the body’s electrolytes, particularly low levels of potassium or magnesium, can further impair the heart’s electrical stability, making it more prone to the effects of QT-prolonging drugs.
Dosage and Combination Products
The dosage of the antihistamine plays a direct role in toxicity, as excessive doses increase the likelihood of channel blockage and subsequent palpitations. Many over-the-counter allergy medications are combination products that include a decongestant, such as pseudoephedrine. These decongestants independently constrict blood vessels, which increases heart rate and blood pressure, creating a separate source of palpitations that compounds the risk.
Seeking Medical Guidance and Prevention
When taking an antihistamine, be aware of symptoms that signal a potential problem and require immediate medical assessment. Palpitations accompanied by chest pain, dizziness, fainting (syncope), or severe shortness of breath warrant emergency attention. If palpitations are persistent, irregular, or involve a sustained, rapid pounding, consult a healthcare professional promptly.
Preventative measures involve careful medication management and awareness of personal health history. Before starting any new antihistamine, consult with a doctor or pharmacist, especially if taking other medications. This screens for potential drug-drug interactions, particularly with known CYP3A4 inhibitors or other drugs that prolong the QT interval.
Reviewing medical history for cardiac conditions, liver or kidney impairment, or electrolyte abnormalities is necessary before use. If cardiac risk is a concern, switching to a newer, second-generation antihistamine is the safest strategy, as these drugs generally lack the hERG-blocking properties of older agents. Always follow the recommended dosage, as overdosage is a common cause of serious cardiac complications.