Antihistamines

Information about Antihistamines

Antihistamines are drugs that are used to prevent or relieve the symptoms of hay fever and other allergies by preventing the action of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, watery eyes, and sometimes can make breathing difficult. Some of these drugs are also used to prevent motion sickness, nausea, vomiting, and dizziness. Since they may cause drowsiness as a side effect, some of them may be used to help people go to sleep.

Antihistamines

Histamine is an important mediator of immediate hypersensitivity reactions acting locally and causing smooth muscle contraction, vasodilation, increased vascular permeability, edema and inflammation. Histamine acts through specific cellular receptors which have been categorized into four types, H1 through H4.

Mechanism of action of Antihistamines

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 ameliorate its local actions. Agents that specially block other H2 receptors are generally referred to as H2 blockers rather than antihistamines.

H1 receptor blockers

H1 receptors are widely distributed and are particularly common on smooth muscle of the bronchi, gastrointestinal tract, uterus and large blood vessels. H1 receptors are also found in the central nervous system. The antihistamines are widely used to treat symptoms of allergic conditions including itching, nasal stuffiness, runny nose, teary eyes, urticaria, dizziness, nausea and cough. Their most common use alone or in combination with other agents is for symptoms of upper respiratory illnesses such as the common cold. The central nervous system effects of antihistamines include sedation and decrease in anxiety, tension and adventitious movements.

Types of antihistamines

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.

Side effects of Antihistamines

The antihistamines have several adverse side effects which are related to their antihistaminic actions. Side effects are, however, usually mild and rapidly reversed with stopping therapy or decreasing the dose. These common side effects include sedation, impaired motor function, dizziness, dry mouth and throat, blurred vision, urinary retention and constipation. Antihistamines can worsen urinary retention and narrow angle glaucoma.

Liver toxicity of Antihistamines

The antihistamines rarely cause liver injury. Their relative safety probably relates to their use in low doses for a short time only. The nonsedating antihistamines, however, are often used for an extended period and several forms have been linked to rare instances of clinically apparent acute liver injury which has generally been mild and self-limiting; the antihistamines most commonly linked to liver injury have been cyproheptadine, cetirizine and terfenadine (which is no longer in clinical use).

FDA approval information for Antihistamines

The first generation oral antihistamines in clinical use (with common brand name(s) and year of approval in the United States, if available) include brompheniramine (Bromphen, Dimetapp), chlorpheniramine (Chlor-Timeton: 1971), carbinoxamine (Palgic), clemastine (Tavist: 1977), cyclizine (Marezine, Bonine: 1966), cyproheptadine (Periactin: 1961), diphenhydramine (Benadryl: 1946), dimenhydrinate (Dramamine), doxylamine (Unisom: 1948), hydroxyzine (Atarax, Vistaril: 1957), meclizine (Antivert: 1957), phenyltoloxamine (Acuflex), promethazine (Phenergan: 1957), and triprolidine (Triafed). Second generation antihistamines in general use and used orally include acrivastine (Semprex-D), cetirizine (Zyrtec: 1995), levocetirizine (Xyzal: 2007), loratadine (Claritin: 1993), desloratadine (Clarinex: 2001), and fexofenadine (Allegra: 1996).

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