ヒスタミンH1受容体遮断薬、ヒスタミンH1受容体拮抗薬、H1遮断薬、H1拮抗薬、抗ヒスタミン薬、抗ヒスタミン剤、H1ブロッカー、抗ヒ剤
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/28 23:17:51」(JST)
H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
In common use, the term "antihistamine" refers only to H1 antagonists, also known as H1-receptor antagonists and H1-antihistamines. It has been discovered that some H1-antihistamines function as inverse agonists, as opposed to receptor antagonists, at the histamine H1-receptor.[1]
In type I hypersensitivity allergic reactions, an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, the histamine can react with local or widespread tissues through histamine receptors.
Histamine, acting on H1-receptors, produces pruritus, vasodilation, hypotension, flushing, headache, bradycardia, bronchoconstriction, increase in vascular permeability and potentiation of pain.[2]
While H1-antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be of life-threatening severity. Additional administration of epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities.
H1-antihistamines are clinically used in the treatment of histamine-mediated allergic conditions. These indications may include:[3]
H1-antihistamines can be administered topically (through the skin, nose, or eyes) 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 cough associated with the common cold, first-generation antihistamine-decongestants 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 "antihistaminic drugs for colds," carried out by the U.S. Army Medical Corps, reported that "there was no significant difference in the proportion of cures reported by patients receiving oral antihistaminic drugs and those receiving oral placebos. Furthermore, essentially the same proportion of patients reported no benefit from either type of treatment."[4]
Adverse drug reactions are most commonly associated with the first-generation H1-antihistamines. This is due to their relative lack of selectivity for the H1-receptor and their ability to cross the blood-brain barrier.
The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H1-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, increased appetite leading to weight gain, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis.[3]
The newer, second-generation H1-antihistamines are far more selective for peripheral histamine H1-receptors and have a better tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth.[3]
These are the oldest H1-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially when compared with the second-generation H1-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes.
The first H1-antihistamine discovered was piperoxan, by Ernest Fourneau and Daniel Bovet (1933) in their efforts to develop a guinea pig animal model for anaphylaxis at the Pasteur Institute in Paris.[5] Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution. Following their discovery, the first-generation H1-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties.
| Class | Description | Examples |
| Ethylenediamines | Ethylenediamines were the first group of clinically effective H1-antihistamines developed. |
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| Ethanolamines | Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, as well as sedation, are observed in this group but the incidence of gastrointestinal adverse effects is relatively low.[3][6] |
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| Alkylamines | The isomerism is a significant factor in the activity of the agents in this group. E-triprolidine, for example, is 1000-fold more potent than Z-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H1-receptor binding site.[6] Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical central nervous system (CNS) stimulation.[3] |
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| Piperazines | These compounds are structurally related to the ethylenediamines and the ethanolamines, and produce significant anticholinergic adverse effects. Compounds from this group are often used for motion sickness, vertigo, nausea, and vomiting. The second-generation H1-antihistamine cetirizine also belongs to this chemical group.[6] |
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| Tricyclics and Tetracyclics | These compounds differ from the phenothiazine antipsychotics in the ring-substitution and chain characteristics.[6] They are also structurally related to the tricyclic antidepressants (and tetracyclics), explaining the H1-antihistaminergic adverse effects of those three drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. The second-generation H1-antihistamine loratadine was derived from compounds in this group. |
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X = N, R1 = R2 = small alkyl groups
X = C
X = CO
Second-generation H1-antihistamines are newer drugs that are much more selective for peripheral H1 receptors as opposed to the central nervous system H1 receptors and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions. The reason for their peripheral selectivity is that most of these compounds are zwitterionic at physiological pH (around pH 7.4). As such, 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, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.[7]
Systemic:
Topical:
Third-generation H1-antihistamines are second-generation antihistamines informally labeled third-generation because the active enantiomer (levocetirizine) or metabolite (desloratadine and fexofenadine) derivatives of second-generation drugs are intended to have increased efficacy with fewer adverse drug reactions. Fexofenadine is associated with a lower risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively[citation needed].
There is some controversy associated with the use of the term "third-generation antihistamines."[8]
Systemic:
Antihistamines (R06)
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| Aminoalkyl ethers |
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| Substituted alkylamines |
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| Substituted ethylenediamines |
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| Phenothiazine derivatives |
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| Piperazine derivatives |
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| Others for systemic use |
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| For topical use |
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Histamine receptor modulators
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| H1 |
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| H2 |
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| H3 |
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| H4 |
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See also: Receptor/signaling modulators • Monoamine metabolism modulators • Monoamine reuptake and release modulators
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Pharmacology: major drug groups
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| Gastrointestinal tract/ metabolism (A) |
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| Blood and blood forming organs (B) |
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| Cardiovascular system (C) |
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| Skin (D) |
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| Genitourinary system (G) |
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| Endocrine system (H) |
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| Infections and infestations (J, P, QI) |
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| Malignant disease (L01-L02) |
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| Immune disease (L03-L04) |
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| Muscles, bones, and joints (M) |
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| Brain and nervous system (N) |
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| Respiratory system (R) |
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| Sensory organs (S) |
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| Other ATC (V) |
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Pharmacomodulation
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| リンク元 | 「抗ヒスタミン薬」「抗ヒ剤」「H1拮抗薬」「H1遮断薬」「H1ブロッカー」 |
| 関連記事 | 「block」「H1」「blocker」「H」 |
| 鎮静性 | 世代 | 一般名 | 商品名 |
| 非鎮静性 | 第二世代 | フェキソフェナジン | アレグラ |
| エピナスチン | アレジオン | ||
| エバスチン | エバステル | ||
| ロラタジン | クラリチン | ||
| セチリジン | ジルテック | ||
| オロパタジン | アレロック | ||
| ベポタスチン | タリオン | ||
| 軽度鎮静性 | アゼラスチン | アゼプチン | |
| メキタジン | ゼスラン | ||
| セチリジン | ジルテック | ||
| 鎮静性 | オキサトミド | セルテクト | |
| ケトチフェン | ザジテン | ||
| 第一世代 | d-クロルフェニラミン | ポララミン | |
| ジフェンヒドラミン | レスタミンコーワ | ||
| クレマスチン | タベジール | ||
| ヒドロキシジン | アタラックス |
| 受容体括抗作用 | イオン電流阻害作用 | 血液脳関門透過性 | ||||||||||
| H1 | ACh | NA | 5-HT | DA | PAF | LT | Ca | Na | K | |||
| 第 | ジフェンヒドラミン | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋＋ | ||||
| 一 | ||||||||||||
| 世 | プロメタジン | ＋＋ | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋＋ | ||
| 代 | クロルフェニラミン | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋＋ | ||||
| 第 | ケトチフェン | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ||||
| 二 | ||||||||||||
| 世 | アゼラスチン | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ||||
| 代 | オキサトミド | ＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋ | ＋ | |||
| 第 | テルフェナジン | ＋＋＋ | ＋ | ＋ | ＋ | ＋ | ＋ | － | ||||
| 三 | ||||||||||||
| 世 | アステミゾール | ＋＋＋ | ＋ | ＋ | ＋ | － | ||||||
| 代 | セチリジン | ＋＋＋ | － | |||||||||