How Antihistamines Work: Why One Family of Medicines Treats Hay Fever, Hives, Nausea and Sleeplessness
What histamine does in the body, how antihistamines block it, why some make you drowsy and others do not, everything they are used for, what they cannot do, and how to use them safely.
Part of the Hay Fever & Allergy Guides.
Key fact: Antihistamines do not stop your body making histamine. They sit on the receptors histamine acts on and hold them switched off, which is why they work best taken before a reaction rather than in the middle of one. Whether an antihistamine makes you drowsy depends almost entirely on one thing: how easily it crosses into the brain.
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See allergy treatments →What histamine does
Histamine is a chemical messenger made and stored by the body. Most of it is packed into mast cells, which sit in the skin, the lining of the nose and airways, the eyes and the gut, and into similar cells in the blood. When the immune system of someone with an allergy recognises pollen, dust mite, animal dander, a food or an insect sting, those cells release their histamine within minutes.
Histamine works by attaching to receptors on other cells, and it has four types of receptor, each doing something different. That is the key to understanding why “antihistamine” covers medicines with such different uses.
| Receptor | Where it is | What histamine does there |
|---|---|---|
| H1 | Blood vessels, nerve endings, airways, and the brain | Itching, sneezing, a runny nose, watery eyes, swelling and redness, wheals on the skin. In the brain, wakefulness and part of the nausea and balance system |
| H2 | The stomach lining | Switches on stomach acid production |
| H3 | The brain and nerves | Regulates the release of histamine and other brain messengers |
| H4 | Immune cells | Involved in inflammation and itch; still mainly a research target |
When people say “antihistamine” they almost always mean an H1 antihistamine, the type used for allergies. H2 antihistamines are a separate group used for acid, covered further down.
How an antihistamine blocks it
An H1 antihistamine has a shape that fits the H1 receptor. It attaches to it and holds it in its “off” position, so that when histamine arrives there is nowhere for it to act. The histamine is still released; it simply has less effect.
Two practical consequences follow from that. First, an antihistamine works best when it is already in place before the histamine arrives, which is why daily use through an allergy season, or taking a dose before a known exposure, works better than waiting for symptoms. Second, an antihistamine only helps with symptoms that histamine causes. Allergic reactions involve many other messengers, and the slower inflammation that blocks a nose or tightens the airways is largely driven by those, not histamine.
| Antihistamine | Starts to work | Lasts | Drowsiness |
|---|---|---|---|
| Cetirizine | Within about an hour | 24 hours | Uncommon; mild in a minority |
| Loratadine | Within one to three hours | 24 hours | Rare |
| Fexofenadine | Within one to two hours | 24 hours | Least of all |
| Chlorphenamine (Piriton) | Within about an hour | 4 to 6 hours | Common |
| Promethazine | Within about an hour | Up to 12 hours | Marked, often into the next day |
How the everyday allergy antihistamines compare head to head for hay fever is set out in hay fever antihistamines compared.
Why some make you drowsy
In the brain, histamine is one of the signals that keeps you awake and alert. An antihistamine that reaches the brain blocks that signal, and the result is drowsiness. Whether it gets there depends on the blood–brain barrier, the protective layer that controls what passes from the blood into brain tissue.
1st gen
Older antihistamines that cross readily into the brain and sedate
2nd gen
Newer ones designed to stay out, so rarely cause drowsiness
24 hrs
How long most second-generation antihistamines last
The older, first-generation antihistamines, such as chlorphenamine, promethazine, diphenhydramine and hydroxyzine, are small, fat-soluble molecules that cross the barrier easily. The newer, second-generation antihistamines, such as cetirizine, loratadine and fexofenadine, were designed to be pumped back out of the brain, so very little reaches it. Fexofenadine is the most effectively excluded, which is why it is the least sedating.
First-generation antihistamines also block another messenger, acetylcholine. These anticholinergic effects explain their other side effects: a dry mouth, blurred vision, constipation, difficulty passing urine, and, in older people, confusion. The same property is part of why some of them help nausea and motion sickness.
Drowsy does not just mean sleepy. Sedating antihistamines slow reaction times and impair driving, and the effect can last into the next morning after a bedtime dose. The sleepy feeling may fade after a few days of regular use, but the impairment can persist. It is an offence to drive while impaired by any medicine, including one bought over the counter.
What antihistamines are used for
Because histamine acts in so many places, antihistamines treat a surprisingly wide range of problems. Which one is used depends on whether the aim is to block allergy symptoms without sedation, or whether the brain effects are part of the point.
| Use | Usually chosen | Worth knowing |
|---|---|---|
| Hay fever and year-round allergic rhinitis | Non-drowsy, once daily | Treats sneezing, itch, runny nose and eyes; not a blocked nose |
| Hives (urticaria) | Non-drowsy, taken regularly | For persistent hives, a clinician may advise a higher than standard dose. See hives: when it is not a bite |
| Insect bites and stings | Non-drowsy by day, sometimes sedating at night | Reduces itch and swelling from the reaction |
| Itchy skin, including eczema and after scabies treatment | Sedating, at night | Helps mainly by aiding sleep; does little for eczema itch itself |
| Itchy, watery allergic eyes | Tablets, or antihistamine eye drops | Drops act directly on the eye surface |
| Mild food allergy reactions | Non-drowsy or chlorphenamine | For itch and hives only, never for breathing or swallowing problems |
| Nausea, vertigo and motion sickness | Cyclizine, cinnarizine, promethazine | Act on the balance and vomiting centres in the brain. See motion sickness tablets |
| Short-term sleeplessness | Diphenhydramine (Nytol), promethazine (Sominex) | Short-term only; the effect wears off within days of regular use. See sleeping tablets in the UK |
The same drug can appear in more than one row. Promethazine, for example, is used for allergy, nausea and sleep, which is a reminder to check the active ingredient of every product you take so that you do not double up by accident.
H2 antihistamines: the ones for stomach acid
H2 antihistamines, such as famotidine, block the histamine receptors in the stomach lining that switch on acid production. They are used for heartburn, indigestion and reflux, and have no effect on allergy symptoms. Equally, allergy antihistamines do nothing for acid. Ranitidine, once the best-known H2 antihistamine, was withdrawn in the UK in 2020 after an impurity was found, which is why it is no longer available. For most people with persistent reflux, a proton pump inhibitor such as omeprazole is now the more common choice.
What antihistamines cannot do
Antihistamines do not treat anaphylaxis. If someone has difficulty breathing, wheezing, a swollen tongue or throat, a hoarse voice, faintness or collapse after a sting, food or medicine, use their adrenaline auto-injector if they have one and call 999. UK resuscitation guidance no longer includes antihistamines in the emergency treatment of anaphylaxis, because they act too slowly and do not reverse the dangerous effects. Giving one must never delay adrenaline.
Beyond emergencies, there are several common situations where an antihistamine is the wrong tool:
| Problem | Why an antihistamine does not fix it | What does |
|---|---|---|
| A blocked nose from hay fever | Caused by slower inflammation, not histamine | A steroid nasal spray. See Avamys vs fexofenadine |
| Asthma and wheeze | Airway narrowing is driven by other messengers | Asthma inhalers |
| A cold | Not an allergic reaction | Time, fluids and simple painkillers |
| Eczema itself | The itch of eczema is mostly not histamine-driven | Emollients and steroid creams |
Using them safely
Second-generation antihistamines are among the safest medicines available without prescription, but a few groups need extra care, mainly with the sedating kind.
| Situation | What to know |
|---|---|
| Pregnancy | Loratadine and cetirizine have the most safety data and are usually preferred if an antihistamine is needed. Check with a pharmacist or midwife first |
| Breastfeeding | Loratadine is often preferred; sedating antihistamines can make a baby drowsy and may reduce milk supply |
| Children | Several are licensed as liquids for young children, such as cetirizine oral solution. Cough and cold remedies containing antihistamines should not be given to children under six. Promethazine must not be given under two |
| Older adults | First-generation antihistamines can cause confusion, falls, constipation and urinary retention, and are best avoided. Long-term use of medicines with anticholinergic effects has been linked with memory problems |
| Glaucoma, an enlarged prostate or epilepsy | Sedating antihistamines need caution; ask a pharmacist |
| Kidney disease | Cetirizine and similar antihistamines may need a lower dose |
| Alcohol and other sedating medicines | Alcohol, opioid painkillers, sleeping tablets and some antidepressants add to the drowsiness of first-generation antihistamines |
| Fexofenadine specifically | Take it with water, not fruit juice, and two hours apart from indigestion remedies containing aluminium or magnesium, which reduce absorption |
Do not take two antihistamines at once unless a clinician has advised it: a second one adds side effects without adding much benefit, and many combination cold, sleep and travel products already contain one.
Not Sure Which Antihistamine Is Right for You?
Our pharmacist independent prescribers can recommend a non-drowsy or sedating antihistamine, or a nasal spray or eye drops where those would work better, after a GPhC-regulated online consultation.
See allergy treatments →Frequently Asked Questions
How do antihistamines work?
Allergic reactions release histamine, which acts on H1 receptors to cause itching, sneezing, a runny nose, watery eyes and hives. An antihistamine attaches to those receptors and holds them switched off, so the histamine has much less effect. It does not stop histamine being released, which is why antihistamines work best taken before exposure rather than once symptoms are established.
Why do some antihistamines make you sleepy?
Histamine is one of the brain signals that keeps you awake. Older, first-generation antihistamines such as chlorphenamine and promethazine cross easily into the brain and block that signal, causing drowsiness. Newer, second-generation antihistamines such as cetirizine, loratadine and fexofenadine are largely kept out of the brain, so they rarely cause drowsiness.
How long do antihistamines take to work?
Most start working within one to three hours. Cetirizine is among the fastest, usually within an hour. Second-generation antihistamines last around 24 hours, so they are taken once a day, while chlorphenamine lasts four to six hours and is taken several times a day.
Can antihistamines treat a severe allergic reaction?
No. Antihistamines do not treat anaphylaxis. If someone has difficulty breathing, swelling of the tongue or throat, faintness or collapse, use their adrenaline auto-injector if they have one and call 999. Antihistamines act too slowly and do not reverse the dangerous effects, and giving one must never delay adrenaline.
Why are antihistamines used for nausea and sleep?
Histamine also acts in the parts of the brain that control balance, vomiting and wakefulness. Antihistamines that reach the brain, such as cyclizine, cinnarizine and promethazine, therefore reduce nausea and motion sickness, and some, such as diphenhydramine and promethazine, are sold as short-term sleep aids.
Is it safe to take antihistamines every day?
Second-generation antihistamines such as cetirizine, loratadine and fexofenadine are generally safe for daily use through an allergy season or longer when needed. Sedating antihistamines are better kept for short-term use, particularly in older adults. If you need an antihistamine every day all year round, it is worth reviewing what is causing your symptoms.
References
- NHS. Antihistamines. nhs.uk
- National Institute for Health and Care Excellence. Clinical Knowledge Summaries: Allergic rhinitis; Urticaria. cks.nice.org.uk
- Joint Formulary Committee. British National Formulary: antihistamines. bnf.nice.org.uk
- Resuscitation Council UK. Emergency treatment of anaphylaxis: guidelines for healthcare providers (2021). resus.org.uk
- UK Teratology Information Service. Use of antihistamines in pregnancy. medicinesinpregnancy.org
- Medicines and Healthcare products Regulatory Agency. Over-the-counter cough and cold medicines for children. gov.uk
- electronic Medicines Compendium. Summaries of Product Characteristics: cetirizine, loratadine, fexofenadine, chlorphenamine, promethazine. medicines.org.uk
Medical disclaimer: This article is for informational purposes only and does not constitute medical advice. Antihistamines do not treat anaphylaxis: in a severe allergic reaction use adrenaline if available and call 999. Sedating antihistamines can impair driving and are not suitable for everyone. Always read the patient information leaflet and consult a qualified healthcare professional for diagnosis and treatment.