Cyclooxygenase 2 (COX-2) inhibitors
Cyclooxygenase 2 (COX-2) inhibitors are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) that specifically target the COX-2 enzyme, which plays a significant role in inflammation and has been linked to various cancers. These medications are primarily utilized in the treatment of colorectal cancers, particularly familial adenomatous polyposis (FAP), but they are also under investigation for their potential benefits in other types of cancer, including breast, prostate, and pancreatic cancers. Popular COX-2 inhibitors include Celebrex (celecoxib), Vioxx (rofecoxib), and Bextra (valdecoxib), which are typically administered orally in capsule or tablet form.
The mechanism of action for COX-2 inhibitors involves blocking the production of prostaglandins, hormones that mediate inflammatory responses. Unlike COX-1, which is present in various tissues and can cause gastrointestinal side effects when inhibited, COX-2 is expressed mainly in response to inflammation and is found in fewer tissues. By selectively inhibiting COX-2, these drugs aim to reduce tumor cell growth and enhance immune responses against cancer without the severe gastrointestinal complications associated with COX-1 inhibition.
However, the use of COX-2 inhibitors is not without risks. They have been associated with increased cardiovascular events, including heart attack and stroke, leading to the withdrawal of certain products from the market. Other side effects may include gastrointestinal issues, kidney toxicity, and allergic reactions. Thus, while COX-2 inhibitors hold promise in cancer treatment and pain management, careful consideration of their risks and benefits is essential.
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Cyclooxygenase 2 (COX-2) inhibitors
ATC CODE: M01AH
DEFINITION: Cyclooxygenase 2 (COX-2) inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that inhibits the COX-2 enzyme, which is involved in inflammation and cancer.
Cancers treated: Primarily colorectal cancers, such as familial adenomatous polyposis (FAP); others under investigation, including breast, head, liver, prostate, neck, lung, nasopharyngeal, ovarian, and pancreatic cancers.
Delivery routes: These drugs are administered orally as either capsules or tablets and can be taken on an at-home basis. Common drugs include Celebrex (celecoxib), Vioxx (rofecoxib), Bextra (valdecoxib), and Consensi (amlodipine or celecoxib).
How these drugs work: The COX enzymes catalyze the production of hormones called prostaglandins, which stimulate cells to produce inflammatory responses. COX-1 is always expressed and is found in many tissues. Its inhibition can reduce inflammation but may also cause serious gastrointestinal side effects. In contrast, COX-2 is expressed only in response to stimulation signals and is present in a limited number of tissues. COX-2 is overexpressed, however, in several cancers, correlating with poorer overall survival. Therefore, COX-2 inhibitors are being investigated for the treatment and prevention of cancer.
COX-2 contributes to tumor growth by enhancing tumor cell proliferation and survival, inhibiting the body’s immune response to cancer, and inducing the development of new blood vessels that feed a tumor and help it spread to other parts of the body. Because the active sites of the COX enzymes differ, COX-2 inhibitors can form tight complexes with COX-2 that dissociate slowly, thereby blocking enzyme activity. These inhibitors only loosely and reversibly bind to COX-1, however, with no effect on its activity. Blocking only COX-2 may reduce tumor cell growth and survival and improve immune responses against tumor cells without the risk of severe gastrointestinal complications as seen with COX-1 inhibition.
Side effects: The major side effects of COX-2 inhibitors are cardiovascular, such as increased risks of blood clots, heart attack, stroke, and high blood pressure. Adverse side effects led to two drugs, Vioxx (rofecoxib) and Bextra (valdecoxib), being removed from the market by the Food and Drug Administration (FDA). COX-2 inhibitors may also cause indigestion, constipation, diarrhea, stomach bleeding, ulcers, and perforation of the stomach or intestines. Long-term administration may result in kidney toxicity and (rarely) liver toxicity. Allergic skin rashes may also occur with celecoxib (Celebrex).
Bibliography
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