COX 2 inhibitors can affect the stomach lining

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COX 2 inhibitors can affect the stomach lining

BMJ 1999;319:1518 ( 11 December )

Deborah fson , San Francisco

http://bmj.com/cgi/content/full/319/7224/1518

A new class of analgesics designed to be less ulcerogenic than

traditional non-steroidal anti-inflammatory drugs may not protect the

gastric lining after all, according to a University of California study

(Nature Medicine 1999;5:1415-23, 1348-9).

Their ulcerogenic effect may stem from their antiangiogenic properties,

and as such they may be useful anticancer drugs.

The analgesics, agents known as selective cyclo-oxygenase-2 (COX 2)

inhibitors, were specifically designed to be less harmful to the gastric

mucosal lining than traditional non-steroidal anti-inflammatory

medications such as aspirin, indomethacin, and ibuprofen, which block

the activity of both cyclo-oxygenase-1 (COX 1) and COX 2 to some extent.

The cyclo-oxygenases are enzymes that catalyse various reactions in

prostaglandin synthesis. Previously, COX 1 was thought to be solely

responsible for catalysing reactions that produced protective

prostaglandinssuch as those involved in maintaining the integrity of the

gastric lining, regulating renal blood flow by keeping the renal blood

vessels open, and maintaining platelet function. Inhibition of COX 1

could therefore produce deleterious as well as anti-inflammatory side

effects.

COX 2, meanwhile, was thought to catalyse the synthesis of painful

prostaglandins such as those mediating inflammation. The theory was that

selective inhibition of COX 2 would yield a safer anti-inflammatory

agent.

Non-steroidal anti-inflammatory drugs are widely used for headache,

menstrual cramps, musculoskeletal pain syndromes, and arthritis.

Additionally, they are widely prescribed for both primary and secondary

prevention of both heart attack and stroke. Recently they have received

attention as useful agents in decreasing the severity of Alzheimer's

disease as well as in possibly preventing the formation of adenomatous

polyps and colon cancer.

Up to a quarter of patients taking these drugs, however, experience side

effects such as gastroduodenal ulcers, delayed wound healing, bleeding,

and perforated ulcers.

Researchers led by Dr of the Veterans Affairs Medical

Center in Long Beach, California, compared the antiangiogenic properties

of a selective COX 2 inhibitor, NS-398, with those of a non-selective

non-steroidal anti-inflammatory drug, indomethacin, in in vitro assays

of angiogenesis using aortic endothelial cells from rats, human dermal

microvascular cells, and endothelial cells from the human umbilical

vein.

Both indomethacin and NS-398 substantially inhibited angiogenesis in all

cell lines studied. The extent of inhibition was similar for both.