Cromoglicate
Encyclopedia
Cromoglicic acid (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 cell
s.
Because of their convenience (and perceived safety), leukotriene receptor antagonist
s have largely replaced it as the non-corticosteroid
treatment of choice in the treatment of asthma
. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.
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.
is another mast cell stabilizer that also works in controlling asthma.
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. 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. 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%) and thus may inhibit the:
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
.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
), cromoglycate (former BAN
British Approved Name
A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...
), or cromoglicate) is traditionally described as a mast cell stabilizer
Mast cell stabilizer
Mast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmacodynamic...
, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
chemicals such as histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
from mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s.
Because of their convenience (and perceived safety), leukotriene receptor antagonist
Leukotriene antagonist
A leukotriene antagonist is a drug that inhibits leukotrienes, which are fatty compounds produced by the immune system that cause inflammation in asthma and bronchitis, and constrict airways....
s have largely replaced it as the non-corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
treatment of choice in the treatment of asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.
History
Cromolyn sodium was discovered by Dr. Roger AltounyanRoger Altounyan
Roger Edward Collingwood Altounyan was an Armenian physician and pharmacologist who pioneered the use of sodium cromoglycate as a remedy for asthma...
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
Khellin
Khellin is a furanochromone, an organic compound which is derivative of chromone and furan. It has lipophilic properties and causes vasodilation . It is found in the plant Ammi visnaga which has been used in Egyptian folk medicine.In Egypt, the plant "Khella" was used for renal colic...
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:- as a nasal sprayNasal sprayNasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
(Rynacrom(UK), Nasalcrom, Prevalin (Netherlands)) to treat allergic rhinitisAllergic rhinitisAllergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
.
- in a nebulizer solution for aerosol administration to treat asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
.
- as an inhalerInhalerAn inhaler or puffer is a medical device used for delivering medication into the body via the lungs. It is mainly used in the treatment of asthma and Chronic Obstructive Pulmonary Disease . Zanamivir , used to treat influenza, must be administered via inhaler...
(Intal) for preventive management of asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
. 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. In the EU it is manufactured without CFCs by Sanofi-Aventis, although it must be imported from Canada for USA residents.
- as eye dropEye dropEye drops are saline-containing drops used as a route to administer medication in the eye. Depending on the condition being treated, they may contain steroids, antihistamines, sympathomimetics, beta receptor blockers, parasympathomimetics, parasympatholytics, prostaglandins, non-steroidal...
s (Opticrom and Optrex Allergy (UK), Crolom) for allergic conjunctivitisAllergic conjunctivitisAllergic conjunctivitis is inflammation of the conjunctiva due to allergy. Although allergens differ between patients, the most common cause is hay fever. Symptoms consist of redness , oedema of the conjunctiva, itching and increased lacrimation...
- in an oral form (Gastrocrom) to treat mastocytosisMastocytosisMastocytosis is a group of rare disorders of both children and adults caused by the presence of too many mast cells and CD34+ mast cell precursors in a person's body.- Classification :Mastocytosis can occur in a variety of forms:...
, dermatographic urticariaDermatographic urticariaDermatographic urticaria is a skin disorder seen in 4–5% of the population and is one of the most common types of urticaria, in which the skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped.-Presentation:The symptoms are thought to be caused by mast cells in...
and ulcerative colitisUlcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
. Another oral product, Intercron (sodium cromoglicate in distilled water, from ZambonZambonZambon Group is a multinational pharmaceutical and chemical company founded in 1906, with headquarter in Bresso , Italy. It operates directly on three continents - Europe, South America and Asia....
France), is used for food allergies.
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." NedocromilNedocromil
Nedocromil sodium is a medication used to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade and as an eye drop under the brand name Alocril...
is another mast cell stabilizer that also works in controlling asthma.
The underlying mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
is not fully understood; for while cromoglicate stabilizes mast cells, this mechanism is probably not why it works in asthma. 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. It is more likely that these work by inhibiting the response of sensory C fibres to the irritant capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
, 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%) 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 cellT cellT cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, eosinophilsEosinophil granulocyteEosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...
) 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
Chromone
Chromone is a derivative of benzopyran with a substituted keto group on the pyran ring. It is an isomer of coumarin.Derivatives of chromone are collectively known as chromones...
.