Antihistamines are ‘good old drugs’ that have a long history of use. H1 antihistamines work on the histamine-1 receptors as inverse agonists or antagonists to provide relief for conditions such as allergic rhinitis, urticaria and motion sickness. H2 antihistamines target receptors primarily in the upper gastrointestinal tract and stomach, providing relief for gastric conditions such as peptic ulcer and acid reflux. Since its discovery in the last century, H1-antihistamines have been topping medication sales billboards, proving to be a safe and effective symptomatic remedy for common ailments. Are antihistamines really a true saviour, or a wolf in sheep’s disguise?

The first antihistamine in history

The first antihistamine was discovered as a voyage experiment to search for a substance that can antagonise histamines. In 1937, scientist Daniel Bovet wrote about the presence of three naturally occurring amines - acetylcholine, epinephrine and histamines, which all have a similar chemical structure. He observed that these chemicals were naturally present in-vivo, and they interfere with the effects of acetylcholine. Bovet's work led to the discovery of the first H1-antihistamine (i.e. antergen) in 1942, followed by diphenhydramine in 1945.

H1 antihistamines in the 21st century

Today, extensive research on H1 antihistamines is conducted, resulting in the development of innumerable chemical structures bearing anti-histaminergic effects in the market. These agents are made into various dosage forms including oral syrup, oral tablet, topical creams and gels as well as nasal sprays. Different chemical compounds have slightly different mechanisms of action, bind to receptors with different affinity, have different absorption and metabolism pharmacokinetics and different side effect profiles. Drug companies tap on these differences as marketable unique selling points to target different audiences.

Antihistamines now – Things to note

1. Easy access, highly affordable and relatively safe

There are few antihistamines that remain as a prescription only medication (POM) in the market. Most are readily available as pharmacy-only (P-only) item or over-the-counter (OTC) item. This ease of purchase has led to a widespread use of antihistamines. Owning to its relatively safe profile, we have seen more antihistamines, especially the non-sedating second generation antihistamines getting delisted from P-only item to OTC status, making it even more accessible to the public. Prices for antihistamines have also skydived from being exclusive to cheap over the past decade due to generics.

2. The “family antihistamine” phenomenon

Allergies have a genetic component. Patients with a history of allergies sometimes come to the pharmacy to ask for an antihistamine not for themselves, but for the family. They reside in the same environment, eat similar food, face the same allergens and sometimes have the same type of allergic reactions. The lack of surveillance of sale of antihistamines, unlike potentially abusive medications, also allows patients to get stock for more than oneself at any one time. Dinnertime conversation exaggerates this phenomenon as family members discuss this miracle medication, which is cheap, good, effective and safe.

3. Creative names for impact

Brand names of medications are created to deliver impact and attract customers. Drug names peppered with tricatives such as X and Z are fast sounding words, implying that these medications work faster. It is no wonder that sometimes patients are more inclined to purchase antihistamines with brand names with such fast sounding tricatives due to the idea of immediate symptomatic relief.

Realise that it is not a one size fit all

Many pharmacists today will applaud the act of delisting antihistamines from P-only to OTC items, as we deemed antihistamines to be relatively safe medications. Second generation antihistamines are especially popular due to the non-sedating side effect profile and long duration of action. However, missing out on the following caveats may endanger a patient.

1. Elderly and antihistamines use

1st generation antihistamines crosses the blood brain barrier and are therefore sedating. We know that they can cause drowsiness and this effect is especially prominent in the elderly. What one often fails to realise is the consequences of the excessive somnolence, leading to avoidable falls and accidents. Antihistamines with anticholinergicity can also worsen glaucoma, constipation, acute urinary retention, all of which are medical conditions commonly present in the geriatric population. They are also more likely to be on medications that can have potential drug interactions with antihistamines such as TCA antidepressants, muscle relaxants and anti-seizure medications. Pharmacists should be vigilant and remind elderly patients of the potential drug and disease interactions with chronic use of antihistamines.

2. Liver and cardiac toxicity

Terfenadine, the first non-sedating antihistamine, marketed for allergic rhinitis was withdrawn from the US market in 1997 due to its potential cardiac toxicity, causing arrhythmia and QTc prolongation. This drug also bears a black box warning of causing liver failure when taken together with liver toxic drugs such as ketoconazole. Today, fexofenadine, a metabolite of its parent prodrug terfenadine, has taken its place in the market for similar indication. Though antihistamines in the market today are deemed to be safe, pharmacists should remain vigilant and informed of possible drug-drug interactions and use of certain antihistamines in patients with cardiac conditions as antihistamines with similar chemical structure can cause similar adverse reactions.

3. Therapeutic duplication with combination medications

Self-medication is becoming more popular with the public being more informed of the use of medications. It is also not uncommon to find antihistamines being present alone or in combination with other ingredients in cold and cough medications, and OTC sleep aid products. Many patients today, however, do not read or fail to understand the ingredients in a combination medication, leading to harmful duplication. Pharmacists should stay cautious of patients taking duplicative antihistamines and perform opportunistic counselling to avoid unnecessary adverse reactions due to repeated active ingredients.

A simple request for an antihistamine in the pharmacy can lead to more than meets the eye. While they are safe, easily available and affordable, healthcare professionals should pay attention to patients with specific health conditions. It is also imperative for pharmacists to perform opportunistic counselling to prevent the duplication of active ingredients in combination medications. MIMS