What is antihistamine

Antihistamines are medicines often used to relieve symptoms of allergies, such as hay fever, hives, conjunctivitis and reactions to insect bites or stings. Antihistamines are also sometimes used as antiemetic to prevent motion sickness and as a short-term treatment for sleeping difficulties (insomnia).

Most antihistamines can be bought over-the-counter (OTC) from pharmacies and shops, but some are only available on prescription. Antihistamine medications are generally administered orally in pill form. Intravenous (IV) and intramuscular (IM) administration are also possible, reserved mostly for in-patient usage for the treatment of specific conditions.

Antihistamines treat these allergy symptoms:

• Congestion, runny nose, sneezing, or itching
• Swelling of the nasal passages
• Hives and other skin rashes
• Itchy, runny eyes

Treating symptoms can help you or your child to feel better during the day and sleep better at night.

Antihistamines are typically separated into sedating (first generation) and nonsedating (second generation) forms, based upon their central nervous system effects, the nonsedating agents being less likely to cross the blood-brain barrier. In addition, some antihistamines have additional anticholinergic, antimuscarinic or other actions. The antihistamines are some of the most commonly used drugs in medicine, and most are available in multiple forms, both by prescription and in over-the-counter products, alone or combined with analgesics or sympathomimetic agents. Common uses include short term treatment of symptoms of the common cold, seasonal allergic rhinitis (hay fever), motion sickness, nausea, vertigo, cough, urticaria, pruritus and anaphylaxis. The sedating antihistamines are also used as mild sleeping aids and to alleviate tension and anxiety. Many antihistamines are also available in topical forms, as creams, nasal sprays and eye drops for local use in alleviating allergic symptoms. The nonsedating antihistamines are typically used in extended or long term treatment of allergic disorders, including allergic rhinitis (hay fever), sinusitis, atopic dermatitis, and chronic urticaria.

Antihistamines are a pharmaceutical class of drugs which act to treat histamine-mediated conditions ¹. There are two main classes of histamine receptors: H-1 receptors and H-2 receptors. Antihistamine drugs which bind to H-1 receptors are generally used to treat allergies and allergic rhinitis. Drugs that bind to H-2 receptors are used to treat upper gastrointestinal conditions that are caused by excessive stomach acid ².

H-1 antihistamines are further classified by the first and second generation agents. First generation H-1 antihistamines cross the blood-brain barrier into the central nervous system (CNS) whereas second-generation H-1 antihistamines do not ¹. The first generation antihistamine drugs will bind to both central and peripheral histamine-1 receptors whereas second-generation drugs only bind to peripheral histamine-1 receptors. This leads to different therapeutic and side effect profiles ³.

U.S. Food and Drug Administration (FDA)-approved Indications ⁴:

H-1 Antihistamines

• Allergic rhinitis
• Allergic conjunctivitis
• Allergic dermatological reaction(s)
• Sinusitis
• Urticaria
• Angioedema
• Atopic dermatitis
• Bronchitis
• Motion sickness
• Nausea
• Vomiting

H-1 antihistamine medications

• First Generation Antihistamines:
  • Brompheniramine
  • Carbinoxamine
  • Chlorcyclizine
  • Chlorpheniramine
  • Clemastine
  • Cyclizine
  • Cyproheptadine
  • Dexbrompheniramine
  • Dexchlorpheniramine
  • Dimenhydrinate
  • Diphenhydramine
  • Doxylamine
  • Hydroxyzine
  • Meclizine
  • Phenyltoloxamine
  • Promethazine
  • Triprolidine

• Second Generation Antihistamines:
  • Acrivastine
  • Cetirizine
  • Fexofenadine
  • Levocetirizine
  • Loratadine
  • Desloratadine

H-2 Antihistamines

• Peptic ulcer
• Acid reflux
• Gastritis

H-2 antihistamine medications

• Cimetidine
• Famotidine
• Nizatidine
• Ranitidine
• Roxatidine

Non-FDA approved uses for H-1 antihistamines include insomnia and for H-2 antihistamines include indigestion.

There are two other classes of histamine receptors: H-3 and H-4. While compounds exist that bind them, there is no specific clinical benefit to the usage of those compounds in humans.

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.

Is benadryl an antihistamine?

Yes. Benadryl is a first generation OTC (over-the-counter) antihistamine

Taking antihistamines with other medicines, food or alcohol

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

There may be a risk the medicines could affect each other, 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 gastro-esophageal reflux disease (GERD) medicines
• cough and cold remedies that also contain an antihistamine

It’s best to avoid alcohol while taking an antihistamine, particularly if you’re taking an older type of antihistamine, as this can increase the chances of it making you feel sleepy.

Food and other drinks don’t affect most antihistamines, but check the leaflet that comes with your medicine to make sure.

What does an antihistamine do

Antihistamines are medicines often used to relieve symptoms of allergies, such as hay fever, hives, conjunctivitis and reactions to insect bites or stings.

Antihistamines also sometimes used to prevent motion sickness and as a short-term treatment for sleeping difficulties (insomnia).

Antihistamines work by stopping a substance called histamine affecting the cells in your body.

Histamine is a chemical released when the body detects something harmful, such as an infection. Histamine is an important mediator of immediate hypersensitivity reactions acting locally and causing smooth muscle contraction, vasodilation, increased vascular permeability, edema and inflammation. But in people with allergies, the body mistakes something harmless, such as pollen, for a threat. It then produces histamine, which causes symptoms such as rashes, a runny nose and/or sneezing. Antihistamines stop this effect by acting as antagonists at the H-1 receptors. The clinical benefit is a reduction in allergy symptoms and any related symptoms ⁵. 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 taken afterwards.

Histamine acts through specific cellular receptors which have been categorized into four types, H1 through H4 receptors. Antihistamines represent a class of medications that block the histamine type 1 (H1) receptors. Importantly, antihistamines do not block or decrease the release of histamine, but rather reduce its local actions. Agents that specially block other histamine type 2 (H2) receptors are generally referred to as H2 blockers rather than antihistamines.

First generation antihistamines cross the blood-brain barrier into the central nervous system and antagonize H-1 receptors, which leads to a different therapeutic and adverse effect profile in contrast to second-generation antihistamines which only bind to peripheral histamine receptors.

The duration of the pharmacological action of first-generation antihistamines is about 4 to 6 hours. In contrast, second-generation antihistamines work for 12 to 24 hours. They are both metabolized by the liver using the P450 cytochrome system.

Parietal cells in the gastrointestinal tract exist to secrete hydrochloric acid. They undergo regulation by acetylcholine, gastrin, and also histamine. The histamine releases from enterochromaffin-like cells. When histamine binds to the H-2 receptors on parietal cells, cyclic adenosine monophosphate (cAMP) increases thereby inducing protein kinase A. This then leads to phosphorylation of the proteins that take part in the transport of hydrogen ions. Increased histamine leads to increased stomach acid secretion ⁶.

The use of antihistamines that are specific to the H-2 receptor blocks the entire process and thereby reduce stomach acid secretion.

Antihistamine drugs

Antihistamines are a class of medications which subdivide into H-1 and H-2 antihistamine categories.

1. H-1 antihistamines, which further subdivide into first and second generations, are primarily used to treat allergic symptoms and illnesses mediated through similar mechanisms.
2. H-2 antihistamines are used to lower excessive stomach acid and thereby treat acid reflux, gastritis, and gastrointestinal ulcers.

H-1 antihistamine medications

• First Generation Antihistamines:
  • Brompheniramine
  • Carbinoxamine
  • Chlorcyclizine
  • Chlorpheniramine
  • Clemastine
  • Cyclizine
  • Cyproheptadine
  • Dexbrompheniramine
  • Dexchlorpheniramine
  • Dimenhydrinate
  • Diphenhydramine
  • Doxylamine
  • Hydroxyzine
  • Meclizine
  • Phenyltoloxamine
  • Promethazine
  • Triprolidine

• Second Generation Antihistamines:
  • Acrivastine
  • Cetirizine
  • Fexofenadine
  • Levocetirizine
  • Loratadine
  • Desloratadine

H-2 antihistamine medications

• Cimetidine
• Famotidine
• Nizatidine
• Ranitidine
• Roxatidine

Types of antihistamine

Antihistamines are usually divided into two main groups:

1. Older antihistamines that make you feel sleepy – such as chlorphenamine, hydroxyzine and promethazine
2. Newer, non-drowsy antihistamines that are less likely to make you feel sleepy – such as cetirizine, loratadine and fexofenadine

They also come in several different forms – including tablets, capsules, liquids, syrups, creams, lotions, gels, eye drops and nasal sprays.

Antihistamine contraindications

Given the potential cardiotoxic (toxic effect on your heart) effects of antihistamines, they are relatively contraindicated in any patient with QT prolongation. Patients using other QT prolonging drugs require careful monitoring for further prolongation of the QT interval, due to the risk of potentially fatal cardiac arrhythmias ⁷.

Usage in pregnant women is a relative contraindication. Additionally, women who are lactating should also avoid antihistamines.

Patients with impaired renal or hepatic function should use antihistamines with caution.

Hypertension, cardiovascular disease, urinary retention, increased ocular pressure are relative contraindications to the usage of antihistamines.

Dosages of the antihistamines require monitoring. The cardiotoxic effects of antihistamines may be monitored on an electrocardiogram (ECG) to assess prolongation of the QT interval.

Over the counter antihistamine

Antihistamines are a class of medications which subdivide into H-1 and H-2 antihistamine categories.

1. H-1 antihistamines, which further subdivide into first and second generations, are primarily used to treat allergic symptoms and illnesses mediated through similar mechanisms.
2. H-2 antihistamines are used to lower excessive stomach acid and thereby treat acid reflux, gastritis, and gastrointestinal ulcers.

Over-the-counter (OTC) antihistamines are medicines that help relieve or prevent allergy symptoms. OTC means you can buy them at a store, without a prescription from your doctor. They are available in pills or liquids, nasal sprays or gels, and eyedrops.

Two types of OTC antihistamines are available: first-generation and second-generation. Both types can be useful for allergies. First-generation antihistamines are sometimes used in OTC cold medicines.

First-generation OTC antihistamines

These were some of the first antihistamines scientists developed. They are cheaper and widely available. They also work in the part of the brain that controls nausea and vomiting. They can help prevent motion sickness. One of the most common side effects of first-generation antihistamines is feeling sleepy. For this reason, they are sometimes used to help people who have trouble sleeping (insomnia).

Some common antihistamines you can buy over the counter include:

• Brompheniramine (brand names include Children’s Dimetapp Cold)
• Chlorpheniramine (brand names include Chlor-Trimeton, Actifed Cold)
• Dimenhydrinate (brand names include Dramamine)
• Diphenhydramine (brand names include Benadryl, Nytol, Sominex)
• Doxylamine (brand names include Vicks NyQuil, Tylenol Cold and Cough Nighttime)

Second-generation OTC antihistamines

These are newer medicines. Many of them provide relief from allergy symptoms without causing side effects, such as sleepiness. Common kinds include:

• Loratadine (brand names include Alavert, Claritin)
• Cetirizine (brand names include Zyrtec)
• Fexofenadine (brand names include Allegra)

Note: Some antihistamines are mixed with other medicines. These could include pain relievers or decongestants. Many of the brand names above are for these combination medicines. These are meant to treat many symptoms at the same time. It is a good idea to treat just the symptoms that you have. If you have only a runny nose, don’t choose a medicine that also treats headache and fever.

Who shouldn’t take OTC antihistamines?

Talk to your doctor before using a first-generation antihistamine if you have any of the following health problems:

• glaucoma
• trouble urinating (from an enlarged prostate gland)
• breathing problems, such as asthma, emphysema, or chronic bronchitis
• thyroid disease
• heart disease
• high blood pressure.

If you have kidney or liver disease, talk to your doctor before taking a second-generation antihistamine.

How do I safely take OTC antihistamines?

Read the directions on the label before taking any medicine. Learn how much to take and how often you should take it. If you have any questions about how much medicine to take, call your family doctor or pharmacist. Keep track of which OTC medicines you are using and when you take them. If you need to go to the doctor, take the list with you.

Follow these tips to make sure you are taking the right amount of medicine:

• Take only the amount recommended on the medicine’s label. Don’t assume that more medicine will work better or quicker. Taking more than the recommended amount can be dangerous.
• If you take a prescription medicine, ask your doctor if it’s okay to also take an OTC antihistamine.
• Don’t use more than one OTC antihistamine at a time unless your doctor says it’s okay. They may have similar active ingredients that add up to be too much medicine.

Healthy adults don’t usually experience side effects from antihistamines. However, side effects can be a concern for older adults or people who have health problems. First-generation antihistamines may make you feel sleepy. This can affect your ability to drive or operate machines. They can make it hard for you to think clearly. Alcohol can increase the drowsiness caused by antihistamines. Antihistamines may cause your mouth and eyes to feel dry. They can also cause abdominal pain and headaches. Second-generation antihistamines are less likely to cause these side effects.

Could OTC antihistamines cause problems with any other medicines I take?

Antihistamines can interact with other medicines you take. Talk to your doctor before taking a first-generation antihistamine if you take any medicines that can make you tired. These include sleeping pills, sedatives, or muscle relaxants.

Antihistamines are often combined with decongestants and/or pain relievers. If you take a combination medicine, it’s important to know each active ingredient. One or more could interact with other medicines you’re taking.

Be sure not to take too much antihistamine. Many OTC cold and allergy medicines contain them already. Some prescription medicines do, too. If you take more than 1 of these medicines, you may get much more antihistamine than is good for you.

Second-generation antihistamines are less likely to interact with other medicines you are taking. Always talk to your doctor if you take other medicines to make sure they are safe.

Best antihistamine

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 more than one type to find one that works for you.

• 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.

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 affect your sleep.

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

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.

Antihistamine side effects

Like all medicines, antihistamines can cause side effects. Antihistamine medications carry a broad range of side effects depending on the specific class of drugs utilized. H-1 receptor antihistamines will generally cause clinically noticeable adverse effects that are dosage dependent. These side effects are far more commonly seen in first-generation antihistamines. Second generation antihistamines do not cross the blood-brain barrier, and therefore their side effect profile is far more limited. In contrast to H-1 receptor antihistamines, H-2 receptor antihistamines do not commonly cause adverse effects except for cimetidine.

H-1 receptor antihistamines have anticholinergic properties which are adverse effect inducing; this principally occurs from the first generation category of antihistamines only. As a whole, they are sedating but may cause insomnia in some users. Due to their anticholinergic properties, dry mouth is a relatively common adverse effect. Some users experience dizziness and tinnitus. At increasing dosages, euphoria and decreased coordination may also occur, and at even higher dose ranges, delirium is a potential adverse effect ⁸. Antihistamines may also be cardiotoxic in some users as they have QT-prolonging effects ⁷.

H-2 receptor antihistamines are generally well tolerated by users but do carry the risk of uncommon side effects. Gastrointestinal changes can be seen, including both diarrhea and constipation. Reports exist of fatigue, dizziness, and confusion. One specific drug in this category that may cause a range of adverse effects is cimetidine. Its antiandrogenic effects correlate with the possible occurrence of gynecomastia in men. In women, it has been known to cause galactorrhea. Other H-2 receptor antihistamines do not exhibit the same properties as cimetidine ⁹.

H-2 receptor antihistamines can cause inhibition of the cytochrome system thereby leading to drug toxicity and interactions with other medications.

Patients who suffer from hemodynamic alterations, increased intraocular pressure or increased urinary retention should use antihistamines with caution as these conditions can become exacerbated.

Side effects of older types of antihistamines can include:

• sleepiness (drowsiness) and reduced co-ordination, reaction speed and judgement – don’t drive or use machinery after taking these antihistamines because of this risk
• dry mouth
• blurred vision
• difficulty emptying your bladder

Side effects of non-drowsy antihistamines can include:

• headache
• dry mouth
• feeling sick
• drowsiness – 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.

Antihistamine overdose

Antihistamine toxicity occurs almost exclusively via oral ingestion. Other forms can include intravenous (IV), intramuscular, and topical, but these forms are rare in households ¹⁰. Populations most at risk for antihistamine toxicity from ingestion of unintentional toxic doses or attempted suicide fall into two categories: the young or the elder ¹¹. With the former, antihistamines can be commonly overly administrated due to their therapeutic sedative properties and worldwide available indications. The latter can be contributed to their sedative properties ¹².

The pathophysiology of antihistamine toxicity varies as the drug has a wide range of therapeutic and toxic effects. Most commonly, ingestion of H1 antihistamines (such as diphenhydramine) manifests as hallucinations or antimuscarinic effects. Rapid IV administration of antihistaminic medications often obtains the hallucinogenic effect. A commonly known mnemonic can help one remember the findings of anticholinergic toxicity: “red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, and full as a flask.” Respectively, this presents with vasodilation and reddening of the skin, anhidrosis and lack of sweat production, hyperthermia due to decreased sweat production, mydriasis causing blurred vision, hallucination and delirium, and urinary retention due to reduced detrusor contraction. Furthermore, diphenhydramine has been shown to potentiate opioid receptors, modulate serotonin function, and enhance the concentration of dopamine ¹³.

Antihistamine toxicity complications:

• Arrhythmias
• Respiratory failure
• Coma
• Rhabdomyolysis
• Hyperthermia
• Seizures

There is no specific antidote used for the treatment of antihistamine overdose ¹. However, physostigmine may be an option if a patient is experiencing delirium due to the anticholinergic effects of the antihistamine ¹.

Antihistamine toxicity key facts

• Remember: “red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, and full as a flask.”
• Brugada-like ECG patterns are seen with anticholinergic toxicity.
• Antihistaminic effects peak after two hours of ingestion.
• Severe sedation could be an initial sign and symptom.
• Many common over-the-counter antihistamines produce false negatives for amphetamines, methadone, and phencyclidine in urinary drug screens.

Antihistamine overdose evaluation

Initially, ECG, temperature, heart rate, respiratory rate, and blood pressure should always be assessed. Further diagnostic testing can be useful as well as unreliable in some aspects of antihistaminic toxicity. Many common over-the-counter antihistamines produce false negatives for amphetamines, methadone, and phencyclidine in urinary drug screens and may lead practitioners down the wrong diagnostic pathways. Extensive testing such as gas chromatography/mass spectroscopy or liquid chromatography/mass spectroscopy can be reliable in determining antihistamine concentrations but are not commonly ordered due to the long diagnostic time. Creatinine and blood urea nitrogen (BUN) to assess kidney function should be assessed as well as beta-hCG or other serum pregnancy test.

If patients are experiencing seizures or have extreme agitation, laboratory testing for creatinine kinase should be routinely obtained and IV benzodiazepines should immediately be administrated and with repeated dosing as needed. If hyperthermic, close monitoring and possible cooling efforts via evaporative methods are indicated. If hypotension occurs, treatment with isotonic fluids should be sufficient measures and should also be administered in the context of rhabdomyolysis. With the findings of worsening QRS complexes or QT intervals concurrent with symptoms, dysrhythmias are indicated to prevent fatal arrhythmias. Administration of 50 mEq of sodium bicarbonate, 2 mg of epinephrine, and IV glucose should be attempted.

Lastly, if anticholinergic symptoms become severe, physostigmine and another anticholinesterase are indicated. These medications function by inhibiting cholinesterase, which degrades acetylcholine within the postsynaptic cleft. Contraindications for physostigmine include widened QRS, asthma and other pulmonary diseases, and bradycardia ¹⁴.

Antihistamine overdose treatment

Proper guidelines exist to guide out-of-hospital management. For diphenhydramine and dimenhydrinate, any ingestion under 7.5 mg/kg in children under the age of 6 and under 300 mg or 7.5 mg/kg for adults and older children. At-home observation is appropriate. If these stated doses fail prompt evaluation to the closest emergency department is needed. Initially, management should include constant cardiac monitoring and initiation of IV access. Activated charcoal administration may be indicated, especially if the patient presents shortly after ingestion of the substance. Attempts to increase renal elimination may tempt to initiate, but due to antihistaminic extensive protein binding and a large volume of distribution, these attempts will be in vain ¹⁵.

Antihistamine overdose prognosis

The outcomes of patients with antihistamine toxicity depend on many factors such as underlying medical condition, the amount of drug ingested and any co-ingestants. The majority of patients do recover fully and are discharged. However, the elderly and children can suffer multiorgan failure from a high dose. The first-generation antihistamines like diphenhydramine are more sedating than most other antihistamines. In addition, there are also reports that this agent is known to cause arrhythmias and seizures.

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