H1 antagonist

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H ₁ antagonist , also called H ₁ blocker , is a class of drugs that blocks the action of histamine at H < > 1 , helps to eliminate allergic reactions. Agents in which the main therapeutic effect is mediated by negative modulation of histamine receptors is called antihistamines; Other agents may have antihistaminergic measures but not the correct antihistamines.

In general usage, the term "antihistamine" refers only to H ₁ -antihistamine. Almost all H ₁ -antihistamines serve as inverse agonists on histamine H ₁ -receptors, compared with neutral antagonists, as previously believed.

Video H1 antagonist

Pharmacology

In type I hypersensitivity allergic reactions, allergens interact with and connect between IgE antibody surfaces in mast cells and basophils. After allergen cross-link Immunoglobulin E, tyrosine kinases rapidly signal into cells, leading to cell degranulation and release of histamine (and other chemical mediators) from mast cells or basophils. Once released, histamine can react with local or widespread tissue via histamine receptors.

Histamine, acting on H ₁ -receptor, produces pruritus, vasodilation, hypotension, redness, headache, bradycardia, bronchoconstriction, increased vascular permeability and pain potential.

While H ₁ -antihistamine helps counteract this effect, they work only when taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects can be life-threatening. Additional epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivity.

Maps H1 antagonist

Clinical use H ₁ -antihistamines

Indication

H ₁ -antihistamine is clinically used in the treatment of histamine-mediated allergies. These indications may include:

• Allergic rhinitis
• Allergic conjunctivitis
• Allergic dermatological conditions (contact dermatitis)
• Rhinorrhea (watery nose)
• Urticaria
• Angioedema
• Diarrhea
• Pruritus (atopic dermatitis, insect bites)
• Anaphylactic reactions or anaphylactoid - just added
• Nausea and vomiting
• Sedation (first generation H ₁ -antihistamine)

H ₁ -antihistamine may be administered topically (via skin, nose, or eye) or systemically, based on the nature of the allergic condition.

The authors of the American College of Chest Physicians Updates on Cough Guidelines (2006) recommend that, for coughs associated with common colds, first-generation antihistamines are more effective than newer non-sedating antihistamines. First-generation antihistamines include diphenhydramine (Benadryl), carbinoxamine (Clistin), clemastine (Tavist), chlorpheniramine (Chlor-Trimeton), and brompheniramine (Dimetane). However, a 1955 study of "antihistamine drugs for colds," conducted by the US Army Medical Corps, reported that "there was no significant difference in the proportion of drugs reported by patients receiving oral antihistamine drugs and those receiving oral placebo. , essentially the same proportion of patients reporting no benefit from either type of treatment. "

Adverse drug reactions

Adverse drug reactions are most often associated with the first generation H ₁ -antihistamine. This is due to their lack of relative selectivity to H _{1 receptor} and their ability to cross the blood-brain barrier.

The most common side effects are sedation; These "side effects" are used in many OTC sleep preparations. Other common side effects in first generation H ₁ -antihistamines include dizziness, tinnitus, blurred vision, euphoria, no coordination, anxiety, increased appetite leading to weight gain, insomnia, tremor, nausea and vomiting , constipation, diarrhea, dry mouth, and dry cough. Rare side effects include urinary retention, palpitations, hypotension, headache, hallucinations, and psychosis.

Newer, second generation H ₁ -antihistamine is much more selective for histamine receptors H ₁ peripheral and has a better tolerability profile compared to first generation agents. The most common side effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth.

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First generation (not selective, classic)

These are the oldest H-3 drugs ₁ and their prices are relatively cheap and widely available. They are effective in relieving allergic symptoms, but are usually sufficient for acetylcholine receptors (anticholinergic) very strong antagonists as well. These agents also typically act in receptors -adrenergic and/or 5-HT receptors. The lack of selectivity of these receptors is the basis of the poor tolerability profiles of some of these agents, especially when compared to the second generation H-15 ₁ -antihistamine. The patient's response and the occurrence of adverse drug reactions vary greatly between classes and between agents in the classroom.

Class

H ₁ -the first histopheramine discovered was piperoxan, by Ernest Fourneau and Daniel Bovet (1933) in their attempt to develop a model of marmot animals for anaphylaxis at the Pasteur Institute in Paris. Bovet then won the 1957 Nobel Prize in Physiology or Medicine for his contribution. After their discovery, the first generation H ₁ -antihistamine was developed in subsequent decades. They can be classified by chemical structure, and agents in these groups have the same properties.

General structural features

• Two aromatic rings, connected to central carbon, nitrogen or CO
• Spacer between center X and amine, usually 2-3 carbon long, linear, ring, branched, saturated or unsaturated
• Amine is replaced by a small alkyl group, for example, CH ₃

X = N, R1 = R2 = small alkyl group
X = C X = CO

• The truth in X can increase the potential and selectivity for H1 receptors
• For maximum potential, two aromatic rings must be oriented to different planes
  • for example, a slightly crimped tricyclic ring system and two aromatic rings lie in different geometry plots, providing a very high potential drug.

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Second generation and third generation (selective, no sedation)

Second generation

The second generation H ₁ -antihistamine is a much more selective new drug for peripheral H ₁ recipes compared to the central nervous system H ₁ receptor and cholinergic receptor. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief to allergic conditions. The reason for their peripheral selectivity is that most of these compounds are zwitterionic at physiological pH (about pH 7.4). Thus, they are very polar, meaning that they do not cross the blood-brain barrier and act mainly outside the central nervous system. However, some second generation antihistamines, especially cetirizine, may interact with psychoactive CNS drugs such as bupropion and benzodiazepines.

Example -

Systemic:

• Astemizole (Hismanal)
• Ketotifen (Zaditor)
• Cetirizine (Zyrtec)
• Loratadine (Claritin)
• Rupatadine (Rupafin)
• Mizolastin (Mizollen)
• Acrivastine (Benadryl Allergy Relief (UK), Semprex (USA))
• Ebastine (Evastin, Kestine, Ebastel, Aleva, Ebatrol)
• Bilastine (Bilaxten)
• Bepotastine (Talion, Bepreve)
• Terfenadine (Seldane (USA), Triludan (UK), and Teldane (Australia))
• Quifenadine (Phencarol, ????????)

Topic:

• Azelastine
• Levocabastine (Livostin)
• Olopatadine (Pazeo)

Third generation

The third generation H ₁ -antihistamines are second generation antihistamines that are informally labeled the third generation because the active enantiomer derivatives (levocetirizine) or metabolites (desloratadine and fexofenadine) of second-generation drugs are intended to increase efficacy with fewer reactions harmful drugs. Fexofenadine is associated with a lower risk of cardiac arrhythmias compared with terfenadine. However, there is little evidence for any benefit of levocetirizine or desloratadine, compared with cetirizine or loratadine, respectively.

There is some controversy related to the use of the term "third generation antihistamine."

Example -

Sistemik:

• Levocetirizine
• Desloratadine
• Fexofenadine (Allegra)

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Peraturan

Over-the-counter

Receptor antagonists H _{are approved for free sales, at least in the United States, including:}

First generation (tranquilizer)

Umum/dipasarkan:

• Brompheniramine (Dimetapp, Dimetane)
• Chlorpheniramine (Chlor-Trimeton)
• Dimenhidrinat (Dramamin, Gravol) - kombinasi diphenhydramine dan 8-chlorotheophylline
• Diphenhydramine (Benadryl)
• Doxylamine (Unisom)

Uncommon/discontinued:

• Chlorcyclizine
• Dexbrompheniramine
• Dexchlorpheniramine
• Methapyrilene
• Phenindamine
• Pheniramine
• Phenyltoloxamine
• Pyrilamine
• Thenyldiamine
• Thonzylamine
• Triprolidin

Second generation (no tranquilizer)

• Cetirizine (Zyrtec)
• Loratadine (Alavert, Claritin)

Third generation (no tranquilizers)

• Desloratadine (Clarinex)
• Fexofenadine (Allegra)
• Levocetirizine (Xyzal)

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References

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External links

• Antihistaminics, H1 at the National Library of Medicine US Medical Subject Headings (MeSH)

Source of the article : Wikipedia