posted July 15, 2000 07:34 PM            

Any information will be greatly appreciated!!

Thanks in advance!

"Arnian"

posted July 15, 2000 07:47 PM            

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Check out my Injection and Syringe Info Page:

http://2thick.elitefitness.com

posted July 16, 2000 03:26 PM            

I am grateful, indeed, for the high measure of understanding and competence, which has been given to this forum by its highly esteemed patrons.

PART ONE OF TWO PART DISCUSSION

Some very interesting questions have been raised regarding the use, dosage and side effects associated with intra-cycle arimidex usage. I want to express a special gratitude to forum members �Dropkick�, �Sanjac�, and �Dr. Jeckyll�, without whose distinguished insight we might seldom see progress.

ENZYMES

Enzymes catalyze virtually every process in the cell, and it shouldn�t be too surprising that enzyme inhibitors are among the most important pharmaceutical agents known. For example, aspirin inhibits a step that changes prostaglandins into pain chemicals. Like many inhibitors, aspirin also affects other reactions � In the case of aspirin, it simultaneously blocks clotting mechanisms.

Does arimidex, (anastrozole), block to any degree the formation of other hormones in addition to estrogen (primarily estradiol)? I will talk about that in a minute here�

There may be a question here about the two broad classes of enzyme inhibitors: reversible and irreversible. So I will attempt to address that as well as the aforementioned�

Of the reversible inhibitors, there are two basic classes: Competitive and Noncompetitive. (There is Uncompetitive inhibition too � but lets skip that one). Competitive inhibition is where you make a chemical that looks like the substrate, and like a key, it fits the enzyme thereby blocking its activity�. Simply put: A competitive inhibitor is in the slot blocking the substrate� The substrate can�t get in there�.. The inhibitor is in the way.

Therapeutically: Patient drinks anti-freeze. Anti-freeze has methanol in there that the alcohol dehydrogenase enzyme can convert to formaldehyde causing blindness and stuff�. If this were my patient, I would consider an ethanol infusion, which gets in there blocking that enzyme from converting methanol to formaldehyde. Result is that the patient gets drunk and safely pee�s out the methanol. (No blindness). Cool huh?!

A noncompetitive enzyme inhibitor doesn�t hook-up at the substrate site � rather it attaches to the enzyme somewhere else� And that somehow causes the enzyme to get all messed up and stuff� (I was warned for using that "F" word!)

All this inhibition talk is really academic. The merits of inhibitor design are in its pharmacokinetics. What you can do is plot these reversible inhibitors on a kinetic �double-reciprocal plot�. This tells the scientist when something acts and how much it acts� how fast it acts on the body and all that kind of stuff� And the bored-out-of-his-mind scientist, notes that in competitive inhibition, by virtue of its slope of action in that kinetic curve plot, (Km/Vmax in the Michaelis-Menton equation), regardless of its concentration, the initial rate of the catalyzed reaction (Vmax), will remain unchanged. Further observation also reveals that when enough substrate is present the probability that an inhibitor molecule will bind is minimized. This effect on the apparent Michaels-Menton constant � Km, (affinity of the enzyme for the substrate in most cases), and the absence of an effect on Vmax, (initial rate of catalyzed reaction), is diagnostic for competitive inhibition.

In noncompetitive inhibition, similar plots of the rate data reveal that the substrates inherent Michaels-Menton constant, (Km), is not altered, but Vmax decreases. By actually lowering the concentration of the active enzyme itself, you can lower the apparent Vmax!

Irreversible inhibitors are pretty permanent. There is a very interesting class of these guys called mechanism-based inactivators, because they utilize the normal enzyme reaction mechanism to inactive that enzyme. Often they are relatively unreactive and designed to bind to an active site of the enzyme � Interestingly enough, this inhibitor is designed to carry out the first few chemical steps of the normal enzyme reaction. Instead of being transformed to the normal product, the inhibitor is converted to a very reactive compound that combines irreversibly with the enzyme.

These type of inhibitors fit a new pharmaceutical drug design fondly referred to as: Rational Drug Design (I�m not making this up folks)! But because the inhibitor is designed to be specific for a single enzyme and is unrective until within that enzyme�s active site, drugs based on this approach are often very effective and have few side effects! [For more boring info on this stuff look into DFMO, (difluoromethylornithine) for the strategic treatment of Trypanosoma brucei rhodesiense, (the causative agent of African Sleeping Sickness) � DFMO is inert in solution; binds to ornithine decarboxylase, and is thereby quickly inactivated.]

PART TWO OF TWO PART DISCUSSION ON ARIMIDEX - THE STORY HEATS UP

SCIENTIFIC RESEARCH AND CITATIONS

This is a problem area � its not enough to read these scientific papers, but you have to consider the source, compare to other studies, and probably see how it works in your own practice!

Case In Point: Last year a study was submitted in JAMA, (Journal of the American Medical Assc.), that said that Andro products REDUCED testosterone production, and INCREASED estrogen production. This raised the eyebrows of several researchers and luminaries in the field! Come to find out it was sponsored by some major designer supplement corporation. So those concerned extracted the study�. And after lots of research and calls to the publishers, they found out a few interesting things: Apparently the data was clouded by nebulous measures � They were using like bizarre derived units of measure with special names and mysterious conversion factors. In summary, we couldn�t tell from the article what the actual volume of testosterone or estrogen production was� Moreover, in time we realized that their reported findings were a result of sample timing and some other smoke-and-mirror efforts to promote their self-serving corporate conclusion.

So what does all this boring stuff have to do with arimidex? Glad you asked!! Last time I checked, Zeneca sponsored at least 18 self-promoting arimidex studies. The Zeneca studies suggested that their good product arimidex does not affect cortisol levels, etc. Could this be like the JAMA studies? I don�t know� How could I? Not until I do the clinical trials myself, and/or examine studies sponsored by others who report similar findings�

It is very possible from the foregoing discussion on mechanism-based inhibitors to have a pretty specific one out there� So maybe arimidex IS highly specific at normal doses.

Another problem: I am aware that several top bodybuilding competitors often utilize 4 grams of various testosterones a week. This much testosterone with orals, taken year round, (thanks largely to continuous GH infusion), makes me question just how much arimidex they take on a daily basis. I would have to think allot! If so, what unreported side effects does heavy arimidex use cause in those competitors? At what point will arimidex alter other hormone levels? or more?

Do you feel symptoms of adrenal insufficiency while on mega-dosese of arimidex? The clinical features of such are often vague. Maybe increased pigmentation on hands, face, back of hands.. elbows... knees.. buccal mucosa, conjunctiva, nails, and skin creases... Even more vague are weakness, anorexia (splism god no), abdominal pain, hypotension, nausea, impaired ability to recover from physical stress, salt craving.. etc..

And then we have anecdotal evidence � that underground talk that led us to our present day treatments for HIV, MS, Lupus, Sarcoidosis, RA, and the rest. If we had ignored what we saw, we wouldn�t be having the successes with those diseases that we have today. Who would have ever thought that anabolic steroids make immunocompromised patients live, and help fight heart disease?

So there we have it, a forum� The vanguard of information being volleyed between creative minds � That I believe leads to new discovery and cures. That is my aim here with all those who honor this forum with their patronage.

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Jeff

Don't look back, life is too short