Antihistamines – Latest Classification of Antihistamine

Antihistamines

Antihistamines are drugs that treat allergic rhinitis and other allergies. Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy. Typically people take antihistamines as an inexpensive, generic, over-the-counter drugs with few side effects. As an alternative to taking an antihistamine, people who suffer from allergies can instead avoid the substance which irritates them. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems that antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Doctors recommend that people talk to them before any longer-term use of antihistamines. Histamine stimulates gastric gland secretion, causing an increased secretion of gastric juice of high acidity. This action is probably due mainly to a direct action on parietal and chief gland cells.

Mechanism of Action

Histamine acts directly on the blood vessels to dilate arteries and capillaries; this action is mediated by both H 1- and H 2-receptors. Capillary dilatation may produce flushing of the face, a decrease in systemic blood pressure, and gastric gland secretion, causing an increased secretion of gastric juice of high acidity. Increased capillary permeability accompanies capillary dilatation, producing an outward passage of plasma protein and fluid into the extracellular spaces, an increase in lymph flow and protein content, and the formation of edema. In addition, histamine has a direct stimulant action on smooth muscle, producing contraction if H 1-receptors are activated, or mostly relaxation if H 2-receptors are activated. Also in humans, the stimulant effect of histamine may cause contraction of the intestinal muscle. However, little effect is noticed on the uterus, bladder, or gallbladder. Histamine has some stimulant effect on duodenal, salivary, pancreatic, bronchial, and lacrimal glands. Histamine also can bind to H3 and H4 receptors which are involved in the CNS/PNS neurotransmitter release and immune system chemotaxis, respectively.

Types

H1-antihistamines

H1-antihistamines refer to compounds that inhibit the activity of the H1 receptor. Since the H1 receptor exhibits constitutive activity, H1-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H1 receptor and heightens the receptor’s activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine’s.

The vast majority of marketed H1-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. Clinically, H1-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H1-antihistamines that readily cross the blood-brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H1-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by both the receptor’s constitutive activity and agonist (i.e., histamine) binding at the H1 receptor.

Second-generation antihistamines cross the blood-brain barrier to a much lower degree than first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness by acting on the central nervous system. Some second-generation antihistamines, notable cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.

Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.

H1 antagonists

Examples of H1 antagonists include:

  • Acrivastine (see Benadryl entry in this section)
  • Azelastine
  • Benadryl is a brand name for different H1 antagonist antihistamine preparations in different regions: acrivastine is the active component of Benadryl Allergy Relief and cetirizine of Benadryl One a Day Relief in the UK; Benadryl is diphenhydramine in the US and Canada.
  • Palestine
  • Bromodiphenhydramine
  • Brompheniramine
  • Buclizine
  • Carbinoxamine
  • Cetirizine (Zyrtec)
  • Chlorodiphenhydramine
  • Chlorphenamine
  • Clemastine
  • Cyclizine
  • Cyproheptadine
  • Dexbrompheniramine
  • Dexchlorpheniramine
  • Dimenhydrinate (most commonly used as an antiemetic)
  • Dimetindene
  • Diphenhydramine (see Benadryl entry in this section)
  • Doxylamine (most commonly used as an over-the-counter drug sedative)
  • Ebastine
  • Embramine
  • Fexofenadine (Allegra)
  • Hydroxyzine (Vistaril)
  • Loratadine (Claritin)
  • Meclizine (most commonly used as an antiemetic)
  • Mirtazapine (primarily used to treat depression, also has antiemetic and appetite-stimulating effects)
  • Olopatadine (used locally)
  • Orphenadrine (a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent)
  • Phenindamine
  • Pheniramine
  • Phenyltoloxamine
  • Promethazine
  • Quetiapine (antipsychotic; trade name Seroquel)
  • Rupatadine (Alergoliber)
  • Tripelennamine
  • Triprolidine
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H1 inverse agonists

The H1 receptor inverse agonists include

  • Cetirizine (does not cross the blood-brain barrier)
    • Levocetirizine
  • Desloratadine (does not cross the blood-brain barrier)
  • Pyrilamine (crosses the blood-brain barrier; produces drowsiness)
  • Agonists: 2-Pyridylethylamine
  • Betahistine
  • Histamine
  • HTML
  • L-Histidine
  • UR-AK49
  • Antagonists: First-generation: 4-Methyldiphenhydramine
  • Alimemazine
  • Antazoline
  • Azatadine
  • Bamipine
  • Benzatropine (benztropine)
  • Bepotastine
  • Bromazine
  • Brompheniramine
  • Buclizine
  • Captodiame
  • Carbinoxamine
  • Chlorcyclizine
  • Chloropyramine
  • Chlorothen
  • Chlorphenamine
  • Chlorphenoxamine
  • Cinnarizine
  • Clemastine
  • Clobenzepam
  • Clocinizine
  • Cloperastine
  • Cyclizine
  • Cyproheptadine
  • Dacemazine
  • Decloxizine
  • Deptropine
  • Dexbrompheniramine
  • Dexchlorpheniramine
  • Dimenhydrinate
  • Dimetindene
  • Diphenhydramine
  • Diphenylpyraline
  • Doxylamine
  • Embramine
  • Etodroxizine
  • Etybenzatropine (ethylbenztropine)
  • Etymemazine
  • Fenethazine
  • Flunarizine
  • Histapyrrodine
  • Homochlorcyclizine
  • Hydroxyethylpromethazine
  • Hydroxyzine
  • Isopromethazine
  • Isothipendyl
  • Meclozine
  • Medrylamine
  • Mepyramine (pyrilamine)
  • Mequitazine
  • Methafurylene
  • Methapyrilene
  • Methdilazine
  • Moxastine
  • Orphenadrine
  • Oxatomide
  • Oxomemazine
  • Perlapine
  • Phenindamine
  • Pheniramine
  • Phenyltoloxamine
  • Pimethixene
  • Piperoxan
  • Pipoxizine
  • Promethazine
  • Propiomazine
  • Pyrrobutamine
  • Talastine
  • Thenalidine
  • Thenyldiamine
  • Thiazinamium
  • Thonzylamine
  • Tolpropamine
  • Tripelennamine
  • Triprolidine
  • Second/third-generation: Acrivastine
  • Alinastine
  • Astemizole
  • Azelastine
  • Bamirastine
  • Barmastine
  • Beastie
  • Bepotastine
  • Palestine
  • Cabastinen
  • Carebastine
  • Cetirizine
  • Clemastine
  • Clemizole
  • Clobenztropine
  • Desloratadine
  • Dorastine
  • Ebastine
  • Efletirizine
  • Emedastine
  • Epinastine
  • Fexofenadine
  • Flezelastine
  • Ketotifen
  • Latrepirdine
  • Levocabastine
  • Levocetirizine
  • Linetastine
  • Loratadine
  • Mapinastine
  • Mebhydrolin
  • Mizolastine
  • Moxastine
  • Noberastine
  • Octane
  • Olopatadine
  • Pristine
  • Pibaxizine
  • Piclopastine
  • Quifenadine (phencarol)
  • Rocastine
  • Rupatadine
  • Setastine
  • Sequifenadine (bicarphen)
  • Talastine
  • Temelastine
  • Terfenadine
  • Capitaine
  • Zepastine
  • Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, RP-5063, ziprasidone, zotepine)
  • Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione)
  • Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
  • Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
  • Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)
  • Unknown/unsorted: Azanator
  • Belarizine
  • Elbanizine
  • Florentine
  • Napactadine
  • Tagorizine
  • Trelnarizine
  • Trenizine

H2

  • Agonists: Amthamine
  • Betazole
  • Dimaprit
  • Histamine
  • HTML
  • Impromidine
  • L-Histidine
  • UR-AK49
  • Antagonists: Bisfentidine
  • Burimamide
  • Cimetidine
  • Dalcotidine
  • Donetidine
  • Ebrotidine
  • Etintidine
  • Famotidine
  • Isolamtidine
  • Lafutidine
  • Lamtidine
  • Lavoltidine (loxtidine)
  • Lupitidine
  • Metiamide
  • Mifentidine
  • Niperotidine
  • Nizatidine
  • Outline
  • Oxmetidine
  • Pibutidine
  • Quisultazine (quisultidine)
  • Ramixotidine
  • Ranitidine
  • Roxatidine
  • Sufotidine
  • Tiotidine
  • Tuvatidine
  • Ranitidine
  • Xaltidine
  • Zolantidine

H3

  • Agonists: α-Methylhistamine
  • Cipralisant
  • Histamine
  • Emetic
  • Immepip
  • Immethridine
  • L-Histidine
  • Methimepip
  • Proxyfan
  • Antagonists: A-349,821
  • A-423,579
  • ABT-239
  • ABT-652
  • AZD5213
  • Basant
  • Betahistine
  • Burimamide
  • Ciproxifan
  • Clobenpropit
  • Conessine
  • Enerisant
  • GSK-189,254
  • Impentamine
  • Iodophenpropit
  • Irdabisant
  • JNJ-5207852
  • MK-0249
  • NNC 38-1049
  • PF-03654746
  • Pitolisant
  • SCH-79687
  • Thioperamide
  • VUF-5681

H4

  • Agonists: 4-Methylhistamine
  • α-Methylhistamine
  • Histamine
  • L-Histidine
  • OUP-16
  • VUF-8430
  • Antagonists: JNJ-7777120
  • Mianserin
  • Seliforant
  • Thioperamide
  • Tolerant
  • VUF-6002

Which type is best?

There’s not much evidence to suggest any particular antihistamine is better than any other at relieving allergy symptoms.

Some people find certain types work well for them and others do not. You may need to try several types to find one that works for you.

Non-drowsy antihistamines are generally the best option, as they’re less likely to make you feel sleepy. But types that make you feel sleepy may be better if your symptoms stop you from sleeping.

Ask a pharmacist for advice if you’re unsure which medicine to try as not all antihistamines are suitable for everyone.

How to take antihistamines

Take your medicine as advised by the pharmacist or doctor, or as described in the leaflet that comes with it.

Before taking an antihistamine, you should know:

  • how to take it – including whether it needs to be taken with water or food, or how to use it correctly (if eye drops or a nasal spray)
  • how much to take (the dose) – this can vary depending on things such as your age and weight
  • when to take it – including how many times a day you can take it and when to take it (some types should be taken before bedtime)
  • how long to take it for – some types can be used for a long time, but some are only recommended for a few days
  • what to do if you miss a dose or take too much (overdose)
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The advice varies depending on the exact medicine you’re taking. If you’re not sure how to take your medicine, ask a pharmacist.

Side effects of antihistamines

Like all medicines, antihistamines can cause side effects.

Side effects of antihistamines that make you drowsy can include:

  • sleepiness (drowsiness) and reduced co-ordination, reaction speed, and judgment – do not drive or use machinery after taking these antihistamines
  • dry mouth
  • blurred vision
  • difficulty peeing

Side effects of non-drowsy antihistamines can include:

  • headache
  • dry mouth
  • feeling sick
  • drowsiness – although this is less common than with older types of antihistamines

Check the leaflet that comes with your medicine for a full list of possible side effects and advice about when to get medical help.

If you think your medicine has caused an unwanted side effect, you can report it through the Yellow Card Scheme.

Taking antihistamines with other medicines, food, or alcohol

Speak to a pharmacist or GP before taking antihistamines if you’re already taking other medicines.

There may be a risk the medicines do not mix, which could stop either from working properly or increase the risk of side effects.

Examples of medicines that could cause problems if taken with antihistamines include some types of:

  • antidepressants
  • stomach ulcer or indigestion medicines
  • cough and cold remedies that also contain an antihistamine

Try not to drink alcohol while taking an antihistamine, particularly if it’s a type that makes you drowsy, as it can increase the chances of it making you feel sleepy.

Food and other drinks do not affect most antihistamines but check the leaflet that comes with your medicine to make sure.

Who can take antihistamines

Most people can safely take antihistamines.

But speak to a pharmacist or GP for advice if you:

  • are pregnant or breastfeeding
  • are looking for a medicine for a young child
  • are taking other medicines
  • have an underlying health condition, such as heart disease, liver disease, kidney disease, or epilepsy

Some antihistamines may not be suitable in these cases. A pharmacist or doctor can recommend one that’s best for you.

Loratadine is usually recommended if you need to take an antihistamine in pregnancy. Loratadine or cetirizine are usually OK to take while breastfeeding.

Always check the leaflet that comes with your medicine to see if it’s safe for you before taking it or giving it to your child.

How antihistamines work

Antihistamines block the effects of a substance called histamine in your body.

Histamine is normally released when your body detects something harmful, such as an infection. It causes blood vessels to expand and the skin to swell, which helps protect the body.

But in people with allergies, the body mistakes something harmless – such as pollen, animal hair, or house dust – for a threat and produces histamine. The histamine causes an allergic reaction with unpleasant symptoms including itchy, watering eyes, a running or blocked nose, sneezing, and skin rashes.

Antihistamines help stop this happening if you take them before you come into contact with the substance you’re allergic to. Or they can reduce the severity of symptoms if you take them afterward.

How Antihistamines Help

Antihistamines treat these allergy symptoms:

  • Congestion, runny nose, sneezing, or itching
  • Swelling of the nasal passages
  • Hives and other skin rashes
  • Itchy, runny eyes
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Treating symptoms can help you or your child to feel better during the day and sleep better at night.

How to Take Antihistamines

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

For many people with allergies, symptoms are the worst around 4 a.m. to 6 a.m. Taking an antihistamine at bedtime may help you or your child feel better in the morning during allergy season.

What Antihistamine is Right for you?

You can buy many different brands and forms of antihistamines without a prescription.

  • Some work for only 4 to 6 hours, while others last for 12 to 24 hours.
  • Some are combined with a decongestant, a drug that dries up your nasal passages.

Ask your health care provider what type of antihistamine and what exact dosage is right for you or your child. Make sure you understand how much to use and how many times a day to use it. Be sure to read the label carefully. Or ask your pharmacist if you have questions.

  • Some antihistamines cause less sleepiness than others. These include cetirizine (Zyrtec), desloratadine (Clarinex), fexofenadine (Allegra), and loratadine (Claritin).
  • Do not drink alcohol when you are taking antihistamines.

Also, remember:

  • Store antihistamines at room temperature, away from heat, direct light, and moisture.
  • Do not freeze antihistamines.
  • Keep all medicines where children cannot reach them.

Most Common Side Effects of Antihistamines

Ask your provider if antihistamines are safe for you or your child, what side effects to watch for, and how antihistamines may affect other medicines you or your child take.

  • Antihistamines are thought to be safe for adults.
  • Most antihistamines are also safe for children over 2 years old.
  • If you are breastfeeding or pregnant, ask your provider if antihistamines are safe for you.
  • Adults who take antihistamines should know how the medicine affects them before driving or using machinery.
  • If your child is taking antihistamines, make sure the medicine is not affecting your child’s ability to learn.

There may be special precautions for using antihistamines if you have:

  • Diabetes
  • Enlarged prostate or problems passing urine
  • Epilepsy
  • Heart disease or high blood pressure
  • Increased pressure in the eye (glaucoma)
  • Overactive thyroid

Side effects of antihistamines may include:

  • Changes in vision, such as blurry vision
  • Decreased appetite
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Feeling nervous, excited, or irritable

When to Call the Doctor

Call your provider if:

  • Your nose is irritated, you are having nosebleeds, or you have any other new nasal symptoms
  • Your allergy symptoms are not getting better
  • You are having trouble taking your antihistamines

References