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Antihistamines
ANTIHISTAMINES are drugs which treat allergic rhinitis and other allergies . Antihistamines
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 drug 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
Antihistamines
are usually for short-term treatment. Chronic allergies increase the risk of health problems which 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. Although typical people use the word “antihistamine” to describe drugs for treating allergies, doctors and scientists use the term to describe a class of drug that opposes the activity of histamine receptors in the body. In this sense of the word, antihistamines are subclassified according to the histamine receptor that they act upon. The two largest classes of antihistamines are H1-antihistamines and H2-antihistamines . Antihistamines
Antihistamines
that target the histamine H1-receptor are used to treat allergic reactions in the nose (e.g., itching, runny nose, and sneezing) as well as for insomnia
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Drug Class
A DRUG CLASS is a set of medications that have similar chemical structures , the same mechanism of action (i.e., bind to the same biological target ), a related mode of action , and/or are used to treat the same disease. In several dominant drug classification systems, these four types of classifications form a hierarchy. For example, the fibrates are a chemical class of drugs (amphipathic carboxylic acids) that share the same mechanism of action ( PPAR agonist ), mode of action (reducing blood triglycerides ), and are used to prevent and to treat the same disease (atherosclerosis ). Conversely not all PPAR agonists are fibrates, not all triglyceride lowering agents are PPAR agonists, and not all drugs that are used to treat atherosclerosis are triglyceride lowering agents. CONTENTS * 1 Comprehensive systems * 2 Chemical class * 3 Mechanism of action * 4 Mode of action * 5 Therapeutic class * 6 Amalgamated classes * 7 Attributes * 8 Legal classification * 9 References * 10 External links COMPREHENSIVE SYSTEMS * Anatomical Therapeutic Chemical Classification System (ATC) - most widely used
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Anatomical Therapeutic Chemical Classification System
The ANATOMICAL THERAPEUTIC CHEMICAL (ATC) CLASSIFICATION SYSTEM is used for the classification of active ingredients of drugs according to the organ or system on which they act and their therapeutic , pharmacological and chemical properties. It is controlled by the World Health Organization Collaborating Centre for Drug Statistics Methodology (WHOCC), and was first published in 1976. This pharmaceutical coding system divides drugs into different groups according to the organ or system on which they act and/or their therapeutic and chemical characteristics . Each bottom-level ATC code stands for a pharmaceutically used substance, or a combination of substances, in a single indication (or use). This means that one drug can have more than one code: acetylsalicylic acid (aspirin), for example, has A01AD05 (WHO) as a drug for local oral treatment, B01AC06 (WHO) as a platelet inhibitor , and N02BA01 (WHO) as an analgesic and antipyretic . On the other hand, several different brands share the same code if they have the same active substance and indications
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ATC Code R06
ATC CODE R06 _ Antihistamines for systemic use_ is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System , a system of alphanumeric codes developed by the WHO for the classification of drugs and other medical products. Subgroup R06 is part of the anatomical group R _Respiratory system_ . Codes for veterinary use (ATCvet codes ) can be created by placing the letter Q in front of the human ATC code: for example, QR06. National issues of the ATC classification may include additional codes not present in this list, which follows the WHO version
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Mechanism Of Action
In pharmacology , the term MECHANISM OF ACTION (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor . Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives . In comparison, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance
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Receptor Antagonist
A RECEPTOR ANTAGONIST is a type of receptor ligand or drug that blocks or dampens a biological response by binding to a receptor rather than provoking the response like an agonist . They are sometimes called BLOCKERS; examples include alpha blockers , beta blockers , and calcium channel blockers . In pharmacology , ANTAGONISTS have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active orthosteric (= right place) site or to allosteric (= other place) sites on receptors, or they may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding. The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors
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Inverse Agonist
In the field of pharmacology , an INVERSE AGONIST is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either. Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists. A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level activity in the absence of any ligand . An agonist increases the activity of a receptor above its basal level, whereas an inverse agonist decreases the activity below the basal level. The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy, and an inverse agonist has < 0% (i.e., negative) efficacy. CONTENTS * 1 Examples * 2 See also * 3 References * 4 Further reading * 5 External links EXAMPLESAn example of a receptor that possesses basal activity and for which inverse agonists have been identified is the GABAA receptor . Agonists for the GABAA receptor (such as benzodiazepines ) create a sedative effect, whereas inverse agonists have anxiogenic effects (for example, Ro15-4513 ) or even convulsive effects (certain beta-carbolines )
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Biological Target
A BIOLOGICAL TARGET is anything within a living organism to which some other entity (like an endogenous ligand or a drug ) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are proteins and nucleic acids . The definition is context-dependent, and can refer to the biological target of a pharmacologically active drug compound , the receptor target of a hormone (like insulin ), or some other target of an external stimulus. Biological targets are most commonly proteins such as enzymes , ion channels , and receptors . CONTENTS * 1 Mechanism * 2 Drug targets * 3 Drug target identification * 4 Databases * 5 See also * 6 References MECHANISMThe external stimulus (_i.e._, the drug or ligand) physically binds to ("hits") the biological target
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Histamine Receptor
The HISTAMINE RECEPTORS are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand . There are four known histamine receptors: * H1 receptor * H2 receptor * H3 receptor * H4 receptor COMPARISON Histamine
Histamine
receptors RECEPTOR MECHANISM FUNCTION ANTAGONISTS H1 Gq * ileum contraction * modulate circadian cycle * itching * systemic vasodilatation * bronchoconstriction (allergy-induced asthma)* H1-receptor antagonists * Diphenhydramine * Loratadine * Cetirizine
Cetirizine
* Fexofenadine
Fexofenadine
* Clemastine H2 Gs ↑ cAMP2+ * speed up sinus rhythm * Stimulation of gastric acid secretion * Smooth muscle relaxation * Inhibit antibody synthesis, T-cell proliferation and cytokine production* H2-receptor antagonists * Ranitidine
Ranitidine
* Cimetidine
Cimetidine
* Famotidine * Nizatidine H3 Gi * Decrease Acetylcholine, Serotonin and Norepinephrine Neurotransmitter
Neurotransmitter
release in CNS * Presynaptic autoreceptors * H3-receptor antagonists * ABT-239 * Ciproxifan * Clobenpropit * Thioperamide H4 Gi * mediate mast cell chemotaxis
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HRH1
3RZE IDENTIFIERS ALIASES HRH1, H1-R, H1R, HH1R, hisH1, histamine receptor H1 EXTERNAL IDS OMIM: 600167 MGI: 107619 HomoloGene: 668 GeneCards: HRH1 GENE ONTOLOGY MOLECULAR FUNCTION • histamine receptor activity • signal transducer activity • G-protein
G-protein
coupled receptor activity CELLULAR COMPONENT • integral component of membrane • membrane • integral component of plasma membrane • plasma membrane • cytosol BIOLOGICAL PROCESS • eosinophil chemotaxis • inositol phosphate-mediated signaling • regulation of vasoconstriction • positive regulation of inositol trisphosphate biosynthetic process • cellular response to histamine • regulation of vascular permeability • phospholipase C-activating G-protein
G-protein
coupled
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HRH2
NM_001131055 NM_022304 NM_001010973 NM_008286 REFSEQ (PROTEIN)NP_001124527 NP_071640 NP_001010973 NP_032312 LOCATION (UCSC) Chr 5: 175.66 – 175.71 Mb Chr 13: 54.19 – 54.24 Mb PUBMED SEARCH Wikidata View/Edit Human View/Edit MouseH2 RECEPTORS are positively coupled to adenylate cyclase via Gs . It is a potent stimulant of cAMP production, which leads to activation of protein kinase A . PKA functions to phosphorylate certain proteins, affecting their activity. The drug betazole is an example of a histamine H2 receptor agonist. CONTENTS * 1 Function * 2 Tissue distribution * 3 Physiological responses * 4 See also * 5 References * 6 Further reading * 7 External links FUNCTION Histamine
Histamine
is a ubiquitous messenger molecule released from mast cells , enterochromaffin-like cells , and neurons . Its various actions are mediated by histamine receptors H1, H2, H3 and H4. The histamine receptor H2 belongs to the rhodopsin -like family of G protein-coupled receptors . It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation
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HRH3
NM_007232 NM_133849 REFSEQ (PROTEIN)NP_009163 NP_598610 LOCATION (UCSC) Chr 20: 62.21 – 62.22 Mb Chr 2: 180.1 – 180.1 Mb PUBMED SEARCH Wikidata View/Edit Human View/Edit MouseHISTAMINE H3 RECEPTORS are expressed in the central nervous system and to a lesser extent the peripheral nervous system , where they act as autoreceptors in presynaptic histaminergic neurons , and also control histamine turnover by feedback inhibition of histamine synthesis and release. The H3 receptor has also been shown to presynaptically inhibit the release of a number of other neurotransmitters (i.e. it acts as an inhibitory heteroreceptor) including, but probably not limited to dopamine , GABA , acetylcholine , noradrenaline , histamine and serotonin . The gene sequence for H3 receptors expresses only about 22% and 20% homology with both H1 and H2 receptors respectively. CONTENTS * 1 Tissue distribution * 2 Function * 3 Isoforms * 4 Pharmacology * 4.1 Agonists * 4.2 Antagonists * 5 Therapeutic potential * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links TISSUE DISTRIBUTION * Central nervous system * Peripheral nervous system * Heart
Heart
* Lungs * Gastrointestinal tract
Gastrointestinal tract
* Endothelial cells FUNCTIONLike all histamine receptors, the H3 receptor is a G-protein coupled receptor
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HRH4
NM_001143828 NM_001160166 NM_021624 NM_153087 REFSEQ (PROTEIN)NP_001137300 NP_001153638 NP_067637 NP_694727 LOCATION (UCSC) Chr 18: 24.46 – 24.48 Mb Chr 18: 13.01 – 13.02 Mb PUBMED SEARCH Wikidata View/Edit Human View/Edit MouseThe HISTAMINE H4 RECEPTOR is, like the other three histamine receptors , a member of the G protein-coupled receptor superfamily. CONTENTS * 1 Tissue distribution * 2 Function * 3 Structure * 4 Ligands * 4.1 Agonists * 4.2 Antagonists * 4.3 Therapeutic potential * 5 References * 6 External links TISSUE DISTRIBUTIONH4 is highly expressed in bone marrow and white blood cells and regulates neutrophil release from bone marrow and subsequent infiltration in the zymosan -induced pleurisy mouse model. It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea. It was also found that H4R exhibits a uniform expression pattern in the human oral epithelium. FUNCTIONThe Histamine
Histamine
H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis . This occurs via the βγ subunit acting at phospholipase C to cause actin polymerisation and eventually chemotaxis. STRUCTUREThe 3D structure of the H4 receptor has not been solved yet due to the difficulties of GPCR crystallization
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Medical Subject Headings
MEDICAL SUBJECT HEADINGS (MESH) is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it serves as a thesaurus that facilitates searching. Created and updated by the United States National Library of Medicine (NLM), it is used by the MEDLINE / PubMed article database and by NLM's catalog of book holdings. MeSH is also used by ClinicalTrials.gov registry to classify which diseases are studied by trials registered in ClinicalTrials.gov. MeSH was introduced in 1960, with the NLM's own index catalogue and the subject headings of the Quarterly Cumulative Index Medicus (1940 edition) as precursors. The yearly printed version of MeSH was discontinued in 2007 and MeSH is now available online only. It can be browsed and downloaded free of charge through PubMed . Originally in English, MeSH has been translated into numerous other languages and allows retrieval of documents from different languages. CONTENTS* 1 Structure * 1.1 Descriptor hierarchy * 1.2 Descriptions * 1.3 Qualifiers * 1.4 Supplements * 2 Use in Medline/ PubMed * 3 Use in ClinicalTrials.gov * 4 Categories * 5 See also * 6 References * 7 External links STRUCTUREThe 2009 version of MeSH contains a total of 25,186 _subject headings_, also known as _descriptors_
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Pharmaceutical Drug
A PHARMACEUTICAL DRUG (also referred to as MEDICINE, MEDICATION, or simply as DRUG) is a drug used to diagnose , cure , treat , or prevent disease . Drug therapy (pharmacotherapy ) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management. Drugs are classified in various ways. One of the key divisions is by level of control , which distinguishes prescription drugs (those that a pharmacist dispenses only on the order of a physician , physician assistant , or qualified nurse ) from over-the-counter drugs (those that consumers can order for themselves). Another key distinction is between traditional small-molecule drugs, usually derived from chemical synthesis , and biopharmaceuticals , which include recombinant proteins , vaccines , blood products used therapeutically (such as IVIG ), gene therapy , monoclonal antibodies and cell therapy (for instance, stem-cell therapies). Other ways to classify medicines are by mode of action, route of administration , biological system affected, or therapeutic effects . An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines
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Allergic Rhinitis
ALLERGIC RHINITIS, also known as HAY FEVER, is a type of inflammation in the nose which occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing , red, itchy, and watery eyes, and swelling around the eyes. The fluid from the nose is usually clear. Symptom onset is often within minutes following exposure and they can affect sleep, the ability to work, and the ability to concentrate at school. Those whose symptoms are due to pollen typically develop symptoms during specific times of the year. Many people with allergic rhinitis also have asthma , allergic conjunctivitis , or atopic dermatitis . Allergic rhinitis is typically triggered by environmental allergens such as pollen, pet hair, dust, or mold. Inherited genetics and environmental exposures contribute to the development of allergies. Growing up on a farm and having multiple siblings decreases the risk. The underlying mechanism involves IgE antibodies attaching to the allergen and causing the release of inflammatory chemicals such as histamine from mast cells . Diagnosis is usually based on a medical history in combination with a skin prick test or blood tests for allergen-specific IgE antibodies. These tests, however, are sometimes falsely positive. The symptoms of allergies resemble those of the common cold ; however, they often last for more than two weeks and typically do not include a fever
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