Is There Greater Inhibition By NSAIDS of the COX 1&2 Enzymes (COX 2 Excluded), or they both Mostly Equal?

Question

I'm Sorry fot Not Being Terribly Clear, the Question is, Are There Signifcant Differences in the Inhibition By NSAIDS (Other than Cox 2 Inhibitors) of the COX 1&2 Enzymes?

Thanks Dale D, I was Wondering if Anybody Would Respond.

Thanks Very Much K, What you Have Written Addresses the Question Very Nicely.

K, Contrary to your Words (Initially), it is Abuntantly Clear that the Question is Not Beyond your Understanding.

Sorry, Abundantly.

K, I personally Strongly Suspect, that you Will Never Be Bored as Long as you Have your Mind.

Answer 1

As you know, this is not my area. So, be aware that info may not be reliably reported or interpreted. Gotta be a great answer when it starts off like this huh?? LOL. I absolutely can't resist interesting challenges, so I wanted to take a shot at this...

Anyway, this is what I've gleaned:

NSAIDs nonselectively inhibit both COX isoforms. Conventional NSAIDs vary though in their relative inhibition of COX-1 and COX-2 enzymes, and the reported ratio of COX-1 to COX-2 specificities for a specific agent can vary by up to 100-fold.

The International Consensus Meeting on the Mode of Action of COX-2 Inhibition (ICMMAC) brought together a bunch of experts in different fields to assess the significance of differential inhibition of COX-1 and COX-2. ICMMAC suggests that a drug is considered COX-2-selective if it inhibits COX-2 but not COX-1 across the entire therapeutic dose range based on whole blood assays. The panel concluded that, according to these criteria, with the exception of rofecoxib and celecoxib, all NSAIDs available (at least in 1999) inhibit both isoenzymes and are COX-nonspecific.

So, sounds like both but effects are not equal and dependent on the drug. Here are some examples relating to differential inhibition:

Rofecoxib, celecoxib, and valecoxib are COX-2-selective inhibitors. These coxibs lack clinically relevant COX-1 inhibition at or above therapeutic levels, though rofecoxib is about 30 times more selective for COX-2 than celecoxib.

Meloxicam, exhibits a high degree of specificity for COX-2 but also inhibits COX-1 at a low dosage (i.e., 7.5 mg/day).

Studies (to do with inhibition of serum thromboxane B2) show that celecoxib at single doses of 100 mg and 400 mg (but not 800 mg), and rofecoxib at doses of 12.5 mg and 25 mg do not inhibit COX-1 to a significant degree compared with placebo; meloxicam (15 mg) and ibuprofen (800 mg) both resulted in significant COX-1 inhibition.

Etoricoxib, a COX-2-selective inhibitor, demonstrates a high degree of COX-2 specificity (106-fold in ex-vivo human blood assays) and has a lower potency of COX-1 inhibition than other reported agents.


http://www.jem.org/cgi/content/full/190/4/445

http://www.spineuniverse.com/displayarticle.php/article2499.html

EDIT: Really?? Kind of cool to contribute to something I know nothing about. Ahhhh, I'm such a geek :-).

EDIT 2: Thanx mdgreg C :-). That's such a nice thing to say. I do love to be challenged. Get reeeeeal bored when I'm not.

EDIT 3: Ahhhhh, gadddd, that's funny. Funny as heck but probably true. Let's hope I can hold onto it for a while anyhow :-).

Answer 2

Different tissues express varying levels of COX-1 and COX-2. Although both enzymes act basically in the same fashion, selective inhibition can make a difference in terms of side-effects. COX-1 is considered a constitutive enzyme, being found in most mammalian cells. More recently it has been shown to be upregulated in various carcinomas and to have a central role in tumorigenesis. COX-2, on the other hand, is undetectable in most normal tissues. It is an inducible enzyme, becoming abundant in activated macrophages and other cells at sites of inflammation.
So NSAIDs exclude COX 2

Answer 3

Nsaids can be selective for COX 2 which is the main target for the drugs as it causes the inflammatory process. However they are not totally selective and have an effect on COX 1.

It depends on the drug you are using. Best look in the BNF if you have a specific one in mind.

COX 1 inhibition can result in peptic ulcer disease and some of the other side effects caused by Nsaids.