Sulindac
Encyclopedia
Sulindac is a non-steroidal anti-inflammatory drug
of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck
as Clinoril.
inflammatory
conditions. Sulindac is a prodrug
, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIDs except for drugs of the COX-2 inhibitor
class . The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.
Its usual dosage
is 150-200 milligrams twice per day, with food. It should not be used by persons with a history of major allergic reactions (urticaria
or anaphylaxis
) to aspirin
or other NSAIDs, and should be used with caution by persons having pre-existing peptic ulcer
disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas.
Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association with familial adenomatous polyposis
, and may have other anti-cancer properties.
Sulindac is an effective tocolytic
and may be used in the treatment of preterm labor. In common with other NSAIDs, sulindac is currently being investigated for its role in the treatment of Alzheimer's disease
.
Since it was found that the sulfoxide functional group can be reduced by methionine sulfoxide reductase A (MsrA)
, a possible anti-oxidative capability is being discussed.
Sulindac inhibits canonical Wnt signaling by blocking the PDZ Domain of the protein dishevelled
.
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
as Clinoril.
Uses
Like other NSAIDs, it is useful in the treatment of acute or chronicChronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
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...
conditions. Sulindac is a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIDs except for drugs of the COX-2 inhibitor
COX-2 inhibitor
COX-2 selective inhibitor is a form of non-steroidal anti-inflammatory drug that directly targets COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration, and is the main feature of celecoxib, rofecoxib and other members of this...
class . The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.
Its usual dosage
Effective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
is 150-200 milligrams twice per day, with food. It should not be used by persons with a history of major allergic reactions (urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
or anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
) to aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
or other NSAIDs, and should be used with caution by persons having pre-existing peptic ulcer
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas.
Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association with familial adenomatous polyposis
Familial adenomatous polyposis
Familial adenomatous polyposis is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when not treated....
, and may have other anti-cancer properties.
Sulindac is an effective tocolytic
Tocolytic
Tocolytics are medications used to suppress premature labor . They are given when delivery would result in premature birth...
and may be used in the treatment of preterm labor. In common with other NSAIDs, sulindac is currently being investigated for its role in the treatment of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Since it was found that the sulfoxide functional group can be reduced by methionine sulfoxide reductase A (MsrA)
MSRA (gene)
Peptide methionine sulfoxide reductase is an enzyme that in humans is encoded by the MSRA gene.-Further reading:...
, a possible anti-oxidative capability is being discussed.
Sulindac inhibits canonical Wnt signaling by blocking the PDZ Domain of the protein dishevelled
Dishevelled
Dishevelled is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors...
.