Cromoglicic acid

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Cromoglicic acid
File:Cromoglicic acid.svg
Systematic (IUPAC) name
5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
Clinical data
Pregnancy
category
  • B
Routes of
administration
topical: oral, nasal spray, inhaled, eye drops
Legal status
Legal status
  • inhaler POM, eye OTC(UK)
Pharmacokinetic data
Bioavailability 1%
Biological half-life 1.3 hours
Identifiers
CAS Number 16110-51-3
ATC code A07EB01 (WHO) D11AH03 R01AC01 R03BC01 S01GX01
PubChem CID 2882
DrugBank APRD00336
ChemSpider 2779
Chemical data
Formula C23H16O11
Molar mass 468.367 g/mol[[Script error: No such module "String".]]
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Cromoglicic acid (INN) (also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate) is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells.

Because of their convenience (and perceived safety), leukotriene receptor antagonists have largely replaced it as the non-corticosteroid treatment of choice. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.[1]


History

Cromolyn sodium was discovered by Dr. Roger Altounyan who was himself a lifelong asthma sufferer. It is considered a breakthrough drug in management of asthma as the patients can be freed from steroids in many cases, however, it is mainly effective as a prophylaxis for allergic and exercise induced asthma, not as a treatment for acute attacks. Dr. Altounyan was investigating certain plants and herbs which have bronchodilating properties. One such plant was Khella (Ammi visnaga) which had been used as a muscle relaxant since ancient times in Egypt. Dr. Altounyan deliberately inhaled derivatives of the active ingredient khellin to determine if they could block his asthma attacks. After several years of trial he isolated an effective and safe asthma-preventing compound called cromolyn sodium.


Preparations

Cromoglicic acid is available in multiple forms:

  • in a nebulizer solution for aerosol administration to treat asthma.
  • as an inhaler (Intal) for preventive management of asthma[2]. The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant. As stocks are depleted, this inhaler preparation will no longer be available to patients.[3]

Mechanism of action

"Cromolyn works because it prevents the release of mediators that would normally attract inflammatory cells and because it stabilizes the inflammatory cells."[5] The underlying mechanism of action is not fully understood; for while cromoglicate stabilizes mast cells, this mechanism is probably not why it works in asthma.[6] Pharmaceutical companies have produced 20 related compounds that are equally or more potent at stabilising mast cells and none of them have shown any anti-asthmatic effect.[6] It is more likely that these work by inhibiting the response of sensory C fibres to the irritant capsaicin, inhibiting local axon reflexes involved in asthma, and may inhibit the release of preformed T cell cytokines and mediators involved in asthma. (see review by Garland, 1991)

It is known to somewhat inhibit chloride channels (37% +/- 7%) [7] and thus may inhibit the:

  • exaggerated neuronal reflexes triggered by stimulation of irritant receptors on sensory nerve endings (e.g. exercise-induced asthma)
  • release of preformed cytokines from several type of inflammatory cells (T cells, eosinophils) in allergen-induced asthma

Note: Another chemical (NPPB: 5-nitro-2(3-phenyl) propylamino-benzoic acid) was shown, in the same study, to be a more effective chloride channel blocker.

Finally it may act by inhibiting calcium influx.

Cromoglicate is classified as a chromone.

References

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de:Cromoglicinsäure

fr:Acide cromoglicique it:Sodio cromoglicato nl:Cromoglicinezuur pl:Kromoglikan dwusodowy

pt:Cromoglicato
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  3. http://www.empr.com/Intal-Inhaler-discontinued/article/141142/
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  5. Werner's Pathophysiology page 224
  6. 6.0 6.1 H. P. Rang et al., Pharmacology, Fifth Edition. (2003) ISBN 0 443 07145 4
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