By Dr. Liji Thomas, MDReviewed by Dr. Jennifer Logan, MD, MPH
- Sedating antihistamines
- Central side effects
- Anticholinergic and alpha-adrenergic side effects
- Cardiac side effects
- Side effects with geriatric use
- Contraindications to sedating antihistamines
- Non-sedating antihistamines
Allergies have gone up by 40% in recent years, and allergy medications are being used more often than ever before. There are various types of allergy drugs. Some are used to control acute attacks whereas others help prevent or alleviate the severity of allergic reactions. Some of them, especially sedating antihistamines and corticosteroids, are known to produce unwanted effects that limit their use in certain conditions.
Image Credit: Lightspring / Shutterstock
Antihistamines act to prevent the action of histamine, a bioactive amine, at one of the histamine receptor, to block itching, swelling, redness, nasal congestion, teary eyes, cough, nausea and dizziness.
Histamine affects smooth muscle and blood vessels, causing smooth muscle spasm and vasodilation. The administration of antihistamines blocks most of these effects, making them the most commonly used drugs in the world.
Antihistamines are drugs which treat allergic rhinitis and other allergies. Image Credit: Studio BKK / Shutterstock
These medications come in handy for a variety of allergic conditions as well as those associated with wakefulness and anxiety. Thus, in addition to treating allergies, they have been used variously to treat cold symptoms, motion sickness, nausea due to other causes, skin allergies, and to induce sleepiness in tense or anxious patients.
Antihistamines may be classified as sedating (first-generation antihistamines), and non-sedating (second-generation antihistamines). Both act on the H1 receptor, but the first-generation drugs act less selectively on other receptors as well. The difference lies in their ability to cross the blood-brain barrier.
These drugs have a common chemical structure with drugs which antagonize muscarinic receptors and cholinergic receptors; some antihypertensive drugs; and some tranquilizers. They are not selective to histamine receptors, as a result. They have anti-muscarinic effects, anti-alpha-adrenergic effects, and anti-serotonin effects.
Sedating antihistamines easily cross the blood-brain barrier, to act on central histamine receptors as well as those located peripherally. There are about 64,000 neurons in the human brain which secrete histamine. These regulate a host of actions, namely:
- Learning and memory
- Regulation of body temperature
- Regulation of heart rate and blood pressure
- Involvement in stress hormone and endorphin release
Central side effects
Since these actions are disrupted by sedating antihistamines, these drugs produce sedation, drowsiness, tiredness, lack of concentration, difficulty in learning and memory tasks, poor examination performance, and difficulty with work or driving due to cognitive and coordination problems. Moreover, users continue to feel tired, inattentive, forgetful, and experience poor motor and sensory performance the morning after a night dose – mostly because histamine reduces the duration of rapid eye movement (REM) sleep.
Anticholinergic and alpha-adrenergic side effects
Moreover, sedating antihistamines also produce effects via their blockade of the cholinergic and alpha-adrenergic receptors, such as urinary retention, constipation, sinus tachycardia, inhibition of bowel motility, agitation, and worsening of narrow-angle glaucoma. They also produce or worsen dryness of the mouth, increase the appetite, and induce tolerance when used beyond 5 days or so.
Blurred vision, pupillary dilation, dryness of the mouth and skin, flushing, delirium and confusion, and hyperthermia comprise the well-known and life-endangering anticholinergic syndrome caused by high doses of these drugs. Many over-the-counter antihistamines contain a decongestant as well, and therefore if the user experiences palpitations, the medication should be stopped.
Cardiac side effects
Astemizole and terfenadine are two H1-antihistamines which prolong the cardiac QT interval, and can produce dangerous irregularities of the heart rhythm such as the characteristic 'torsades des pointes' in the ventricular myocardium. These are not approved for use in most countries currently, as a result. This issue is also seen with large doses or overdoses of certain sedating antihistamines like brompheniramine, promethazine, or diphenhydramine.
Side effects with geriatric use
These drugs should be used cautiously in older patients because they typically have lower numbers of cholinergic neurons in the brain, have fewer cholinergic receptors, have compromised renal and liver function, and a less stable blood-brain barrier, with increasing age. Even at lower doses, they can produce dizziness, lowering of blood pressure, and sedation carrying over to the next day. This can cause older adults to fall with related injury risks.
About 25% of older people (over 65 years) have some cognitive decline, even if this is subtle or unnoticed. These individuals may respond badly to antihistamines with pronounced anticholinergic effects, and may show signs of dementia as a result.
Delirium or impaired cognition are other associated side effects with the use of sedating antihistamines in older people. This may further result in inappropriate treatment with antipsychotics, and committal to long-term care facilities with hallucinations and other signs of agitation or aggression, caused by the anticholinergic drugs.
Doctors and other healthcare professionals, as well as older patients, should avoid these drugs now that non-sedating antihistamines are available.
Contraindications to sedating antihistamines
These drugs should be avoided in very young children and in conditions like:
- urinary retention due to benign prostatic hyperplasia
- closed-angle glaucoma
- cardiac disease
They should be used with caution and only if essential, in patients with:
- xerostomia or dryness of the mouth
- chronic obstructive lung disease
- renal disease
- liver disease
- benign prostatic hyperplasia, which is associated with chronic urinary retention
- patients on antidepressants or seizure medication should also consult their doctors before taking antihistamines
- In patients who drink alcohol
With the availability of second-generation antihistamines, the older sedating antihistamines should be avoided if possible. In any case, individuals who are about to write examinations, who are learning exacting materials or tasks, and adults who must fly, drive or work at any task requiring focused concentration should avoid using these drugs.
These are also called second-generation H1-antihistamines, and include loratadine, fexofenadine, mizolastine, ebastine, azelastine, cetirizine, desloratadine, and levocetirizine. These have no currently known cardiac side effects.
Fexofenadine and desloratidine, which, along with levocetirizine, are the most commonly used non-sedating antihistamines, cause very little sedation, as they do not cross the blood-brain barrier to any significant extent and thus have little effect on histamine receptors in the brain. Their failure to cause central sedation is due to their interaction with a pump protein, P-glycoprotein, which inhibits their translocation across the blood-brain barrier. Levocetirizine may produce sedation in a percentage of patients, though it needs to be taken at higher than recommended doses for this.
With their freedom from off-target effects, the non-sedating antihistamines are much more suitable for patients who need long-term therapy. Not only are they safer, but they have a more potent anti-allergic effect.
Non-sedating antihistamines can rarely cause acute liver injury. Although the liver damage is typically mild, if it occurs, antihistamines should be stopped. The liver function is usually only slightly deranged, and returns to normal with substitution of another antihistamine or cessation of the therapy. Thankfully, stopping these drugs produces prompt reversal of most of these side effects, which are typically mild.
The newer antihistamines are generally safe, but should be avoided in children and in pregnancy unless essential.
- Pharmacology of antihistamines. Martin K. Church and Diana S. Church. Indian Journal of Dermatology. 2013 May-Jun; 58(3): 219–224. doi: 10.4103/0019-5154.110832. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667286/
- Coggins, Mark D. Antihistamine risks. Today’s Geriatric Medicine. https://www.todaysgeriatricmedicine.com/archive/0313p6.shtml
- Livertox.nih.gov. (2019). Cetirizine and levocetirizine. https://livertox.nih.gov/Cetirizine_Levocetirizine.htm
- Livertox.nih.gov. (2019). Antihistamines. https://livertox.nih.gov/Antihistamines.htm
- Mayoclinic.org. Allergy medications: know your options. www.mayoclinic.org/.../art-20047403
- Smith N., et al., (2015). Long-term antihistamine therapy revisited. SA Pharmaceutical Journal. https://www.researchgate.net/publication/283758657
- Drugoffice.gov.hk. (2012). Oral anti-allergy medicines. www.drugoffice.gov.hk/.../dm_08.html#e
- Simsek A. et al., (2016). The effect of long-term use of intranasal steroids on intraocular pressure. Clinical Ophthalmology. https://dx.doi.org/10.2147%2FOPTH.S106392.
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How do you know when to stop antihistamines? ›
While there's no set timeline for when someone should stop taking an antihistamine, one should speak to a doctor or drug rehabilitation specialist if they feel like they have become addicted to your antihistamine. The severity and length of an antihistamine withdrawal will depend on the specific drug.What happens if you suddenly stop taking antihistamines? ›
The main withdrawal symptom is called pruritus— itching and burning sensations of the skin ranging from moderate to severe. Other antihistamine withdrawal symptoms include interruptions in sleep patterns.Do you have to wean off antihistamines? ›
In general, wean gradually by 25-50% of the daily dose every 1-4 weeks. If reason for deprescribing is serious adverse effects, wean faster or cease immediately.How long is too long to take antihistamines? ›
First-generation antihistamines come with an increased risk of certain side effects and drug interactions, so are not generally advised for long-term usage. “With first-generation antihistamines, some people note decreasing effectiveness if used daily for several days,” says Dr. Lin.Can you become dependent on antihistamines? ›
Sometimes this effect is mistakenly called an addiction; no, you're not becoming addicted to your allergy medication, but your tissues can become used to the effect of the medication. The result is that, when the dose wears off, you can feel a little worse.Is it OK to take antihistamine everyday? ›
Depending on your symptoms, you can take antihistamines: Every day, to help keep daily symptoms under control. Only when you have symptoms. Before being exposed to things that often cause your allergy symptoms, such as a pet or certain plants.Should I stop taking allergy medicine? ›
When is it safe to stop taking seasonal allergy medications? There is no one-size-fits-all answer to this question. Everyone's experience with seasonal allergies is different and can change from year to year. Stopping too early can cause your symptoms to suddenly appear and be difficult to get back under control.Can antihistamines cause anxiety? ›
Antihistamines are known to cause extreme drowsiness; however, in certain people, they can cause insomnia, excitability, anxiety, restlessness, and a rapid heart rate.Can you get hives from antihistamine withdrawal? ›
Stopping Cetirizine Produces Unbelievable Itching:
Like many others, I experienced severe itching and hives all over my body when I stopped taking it. One tablet would cover 36 hours free of symptoms. However, if I missed taking it right before the time limit, my skin started itching and hives would develop.
Natural antihistamines may help you control your seasonal allergies. Common ones are stinging nettle, vitamin C, quercetin, butterbur, bromelain, and probiotics. Some alternative practices—such as acupuncture, nasal irrigation, and exercise—may also help you manage symptoms.
Do antihistamines raise blood pressure? ›
Determining which allergy medications can raise your blood pressure comes down to the ingredients. Most antihistamines are safe for people with hypertension. But decongestants should be avoided, since they can raise your blood pressure further.When should I stop taking Zyrtec? ›
See your doctor if your mild allergy symptoms have not improved after three days of treatment with Zyrtec, or if your hives persist for more than six weeks despite taking Zyrtec. Discontinue Zyrtec once your allergy symptoms have resolved.Which is the safest antihistamine? ›
Claritin and Zyrtec are effective and safe for most people with minor allergies. However, as with all medications, there may be some side effects. Loratadine—present in Claritin—may not be safe for people with severe liver conditions.How do I stop histamine reaction? ›
Antihistamines block histamine activity, seeking to stop the allergic reaction. Many allergy medications on the shelves of your local drugstore work as antihistamines. But there are also certain foods and plant extracts that may similarly block the effects of histamine.How many times should you take antihistamine? ›
Adults—25 to 100 milligrams (mg) three or four times a day as needed. Children 6 years of age and older—12.5 to 25 mg every six hours as needed. Children 4 to 6 years of age—12.5 mg every six hours as needed. Children and infants up to 4 years of age—Use is not recommended .Can I take antihistamine all year round? ›
Because antihistamines like Claritin and Zyrtec are now available over the counter, we can trust that they're generally safe for longterm use, says Shih.Do antihistamines have long term side effects? ›
Commonly used first-generation antihistamines have strong anticholinergic properties, and recently published data from the adult population have suggested that long-term use of these drugs may increase the risk for developing dementia.What do antihistamines do to the brain? ›
They work on histamine receptor in the brain and spinal cord along with other types of receptors. Most notable about this generation of antihistamines is that they cross the blood-brain barrier, which results in drowsiness.How long does allergy medicine stay in your system? ›
Although everybody processes medications differently, diphenhydramine, loratadine, and cetirizine are likely eliminated from your body about 2 days after your last dose. However, some studies have shown that loratadine and cetirizine may have residual effects for 1 to 4 days after stopping daily use.Does antihistamine make you tired? ›
Antihistamines, mainly used to treat symptoms of hay fever or other allergies, can induce drowsiness by working against a chemical produced by the central nervous system (histamine). These medications can be useful in certain situations, such as for treating sleeplessness related to travel.
Can antihistamines be taken long term? ›
Non-sedating antihistamines are used in the long-term control of allergy, as in hay fever, eczema, sinusitis, and chronic urticaria. No serious side effects have been reported. Tolerance is not a problem.Is it good to change antihistamines? ›
Newer “second-generation” antihistamines including Claritin, Zyrtec, and Allegra are generally safe to use regularly. However, Nimmagadda says, some people find that a given antihistamine becomes less effective over time. Rather than increasing the dose, he recommends switching to a different antihistamine.What does high histamine feel like? ›
These include: Flushing, difficulty regulating body temperature, sudden excessive sweating. Hives, rashes, swelling, itchy skin, eczema. Racing heart, palpitations, arrhythmia.Why do antihistamines make you feel weird? ›
Unrelated to the immune system, histamine is also produced in the brain, where it plays an important part in feeling awake. Antihistamines used to treat respiratory symptoms can get into the brain and interrupt this work, making you feel drowsy.Can antihistamines cause health problems? ›
Side effects of antihistamines
sleepiness (drowsiness) and reduced co-ordination, reaction speed and judgement – do not drive or use machinery after taking these antihistamines. dry mouth. blurred vision. difficulty peeing.
But with this acute itching, a different type of cell in the bloodstream transmits itch signals to the nerves. Those cells produce too much of another non-histamine substance that triggers itch; therefore, antihistamines don't work in response to such signals.How long does antihistamine withdrawal itching last? ›
"Itching can occur within one-two days of stopping Zyrtec or Xyzal after long term daily use (months to years). It usually lasts a few days and then resolves. The intensity of the itching can be from mild to severe. Occasionally, a brief burst of oral steroids may be needed to help the patient get off the drug.What happens when you stop taking cetirizine? ›
However it's best to take cetirizine only for as long as you need to. If you take it regularly over a long period there's a very small chance of severe itching if you stop treatment suddenly. If you've been taking cetirizine every day for a long time, talk to your doctor before stopping it.What is the most common side effect of antihistamines? ›
Side effects of antihistamines
sleepiness (drowsiness) and reduced co-ordination, reaction speed and judgement – do not drive or use machinery after taking these antihistamines. dry mouth. blurred vision. difficulty peeing.
When is it safe to stop taking seasonal allergy medications? There is no one-size-fits-all answer to this question. Everyone's experience with seasonal allergies is different and can change from year to year. Stopping too early can cause your symptoms to suddenly appear and be difficult to get back under control.
How do I stop histamine reaction? ›
Antihistamines block histamine activity, seeking to stop the allergic reaction. Many allergy medications on the shelves of your local drugstore work as antihistamines. But there are also certain foods and plant extracts that may similarly block the effects of histamine.How often can I take antihistamine? ›
Adults—1 to 2 milligrams (mg) every eight to twelve hours as needed. Children 12 years of age and older—0.5 mg to 1 mg two times a day as needed. Children 4 to 12 years of age—Use and dose must be determined by your doctor. Children and infants up to 4 years of age—Use is not recommended .What are symptoms of too much antihistamine? ›
In overdose symptoms can include dizziness, tachycardia, headache drowsiness or agitation. While the current generation of lesser sedating antihistamines do not affect the QT interval at normal doses (unlike the previous generation of medicines), there are concerns there may be some effect in overdose.Which is the safest antihistamine? ›
Claritin and Zyrtec are effective and safe for most people with minor allergies. However, as with all medications, there may be some side effects. Loratadine—present in Claritin—may not be safe for people with severe liver conditions.What conditions should cause a patient to avoid the use of antihistamines? ›
Hypertension, cardiovascular disease, urinary retention, increased ocular pressure are relative contraindications to the use of antihistamines.How long should you take allergy medicine? ›
Most OTC medicines, including antihistamines and nasal steroids, are safe to use as directed for as long as your symptoms last, but there are some exceptions. Don't use a decongestant nasal spray for more than 3 days unless your doctor says to.How long does allergy medicine stay in your system? ›
Although everybody processes medications differently, diphenhydramine, loratadine, and cetirizine are likely eliminated from your body about 2 days after your last dose. However, some studies have shown that loratadine and cetirizine may have residual effects for 1 to 4 days after stopping daily use.Can antihistamines be taken long term? ›
Non-sedating antihistamines are used in the long-term control of allergy, as in hay fever, eczema, sinusitis, and chronic urticaria. No serious side effects have been reported. Tolerance is not a problem.Does water flush out histamine? ›
Water does aid in the removal of histamines from the body as more that 95% of excess histamines are removed from the body through the urine. Drinking adequate amounts of water helps keep histamines at safe and healthy levels that your body can process efficiently.What time of day is histamine highest? ›
Histamine levels are another potent downstream target. Allergic symptoms exacerbate during nighttime and plasma histamine levels exhibit nocturnal peaks. In mastocytosis patients, peak levels of plasma histamine were observed in the early morning with the lowest in the afternoon (19).
What is a natural antihistamine? ›
Summary. Natural antihistamines may help you control your seasonal allergies. Common ones are stinging nettle, vitamin C, quercetin, butterbur, bromelain, and probiotics. Some alternative practices—such as acupuncture, nasal irrigation, and exercise—may also help you manage symptoms.What do antihistamines do to the brain? ›
Diphenhydramine (e.g., Benadryl®) is a first-generation antihistamine medication . In addition to treating allergy and cold symptoms such as sneezing and watery eyes, it also blocks the actions of acetylcholine. This is a neurotransmitter that is important for brain functions including learning and memory.Do antihistamines damage liver? ›
Non-sedating antihistamines can rarely cause acute liver injury. Although the liver damage is typically mild, if it occurs, antihistamines should be stopped. The liver function is usually only slightly deranged, and returns to normal with substitution of another antihistamine or cessation of the therapy.What drugs should not be taken with antihistamines? ›
You shouldn't take prescription antihistamines if you also are taking certain other prescription medicines. These include erythromycin (an antibiotic), or certain medicines used to treat fungal infections. These include itraconazole or ketoconazole.