From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: misc.health.alternative,sci.med,sci.med.pharmacy
Subject: Re: Celebrex (Panacea)
Date: 20 Dec 1998 07:18:28 GMT

In <Pine.GSO.3.95qL.981219081756.14066B-100000@merhaba.cc.columbia.edu>
Aaron Andrew Fox <aaf19@columbia.edu> writes:

>On Fri, 18 Dec 1998, Steve Newport wrote:
>
>> In the UK paper Daily Mail on December 15, Good Health section there
>> was an article on a new 'wonder drug' with NO side effects ( it has
>> been specifically tested' so they say, to confirm that there are no
>> side effects.
>>
>> It is said to work as a pain relief and anti-inflammatory agent based
>> on its action in inhibiting the action of the Cox-2 enzyme.
>>
>> Anybody any comments ?
>
>
>There was a long article on Celebra (as I believe it is called) in the
>*New Yorker* about 6 months back.  Yep.  A new non-steroidal
>anti-inflammatory drug with few if any side effects (in very large scale
>clinical trials) which is *much* more powerful than any existing NSAID
>against pain, and which appears to have the delightful long-term bonus
>effects of delaying and ameliorating both Alzheimer's disease and colon
>cancer.  If I remember the article correctly, it said that clinical trials
>had included 10,000 patients.
>
>Peddlers of acupuncture, massage, magnets, and chiropractic are all
>shaking in their boots.  For years they have sold their services on the
>basis of the negative claim that NSAIDs have gastric side effects, with
>very scant evidence of their positive claims (except for acupuncture) that
>they work better for pain relief.  Take away the side effects ofNSAIDs,
>multiply the power, and it's gonna cost them a lot of $$$$$ when
>suffering people discover they can take a simple pill that is completely
>safe, has long term benefits, and kills big-time pain with nocognitive
>side effects. Poor babies.  They'll probably be accusing the FDA/AMA
>conspiracy of releasing Celebra just to put them out of business.  I wish
>it were so.


Comment:


   On the other hand, please remember that all newly released drugs are
destined to go through the three "P" phases, as outlined by Pharm. D.
Louis Goodman:

1) Panacea Phase.  Best thing since sliced bread; miracle cure!  My
God, they should put this stuff in the water supply.  Think Tagamet,
Prozac, Viagra, etc.

2) Pandora Plague Phase.  Reports of unsuspected side effects come in.
Gynecomastia, drug interactions, suicide, seratonin syndrome, death by
heart attack, vision problems, etc., etc.  Serious wondering now if we
should ever have approved the stuff at all.


Finally, if the drug survives the backlash (which is usually worse in
direct proportion to the hype of the first phase), it at last enters
the:

3) Perfectly Pedestrian Pharmaceutical Phase.  Doctors learn how to use
it, and who not to use it on, and it becomes clear after much placebo
effect wears off, that it's an improvement in technology, but not the
be-all and end-all cure (think AZT).  Though it *will* be a miracle for
a small fraction of people who take it, just as it's a monster drug and
thing from Hell for a few others.   Particularly good drugs that aren't
oral antibiotics or addictive or really poisonous in small overdose,
finally make it to Nirvana (OTC status; no prescription needed) after
making their makers a billion.  Tagament is one, miconozole another,
and I suspect that Diflucan and even Prozac will eventually make it to
Drug Heaven (heretical and strange this may sound now, but there are
those of us who remember how strange OTC miconozole and
cimetidine/Tagamet once seemed).

    Unreleased drugs with lots of promise (your paragraph about
Celebra) by definition are stuck in the Panacea Phase.   "Use the new
drugs quickly, young man," said my old professors, "before they lose
their potency."  Regarding Celebrex, I can only say: just wait.


                                          Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Cerebrex - anti-inflammatory
Date: 22 Feb 1999 09:20:26 GMT

In <sbelknap-210219992128457325@dbts184.uicomp.uic.edu> "Steven
Belknap, M.D." <sbelknap@uic.edu> writes:

>Well, you folks are partially right. The brand name of the drug is
>Celebrex (celecoxib), which is the COX-2 inhibitor. Not to be confused
>with two other sound-alike drugs, one an anticonvulsant (Cerebryx or
>fosphenytoin), the other an antidepressant (Celexa). Now there's a
>medication error just waiting to happen.



ROFL.  Yeah, like Prozac and Prilosec, both 20 mg once a day.  A lot of
people with stomach problem had their depression go away but stomach
problems return, and vice versa.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Cerebrex - anti-inflammatory
Date: 27 Feb 1999 23:07:48 GMT

In <sbelknap-260219992235177201@dbts181.uicomp.uic.edu> "Steven
Belknap, M.D." <sbelknap@uic.edu> writes:

>[[ This message was both posted and mailed: see
>   the "To," "Cc," and "Newsgroups" headers for details. ]]
>
>In article <7ar7gq$koo@dfw-ixnews11.ix.netcom.com>, Steven B. Harris
><sbharris@ix.netcom.com(Steven> wrote:
>
>> In <sbelknap-210219992128457325@dbts184.uicomp.uic.edu> "Steven
>> Belknap, M.D." <sbelknap@uic.edu> writes:
>> >
>> >Well, you folks are partially right. The brand name of the drug is
>> >Celebrex (celecoxib), which is the COX-2 inhibitor. Not to be confused
>> >with two other sound-alike drugs, one an anticonvulsant (Cerebyx or
>> >fosphenytoin), the other an antidepressant (Celexa). Now there's a
>> >medication error just waiting to happen.
>>
>>
>>
>> ROFL.  Yeah, like Prozac and Prilosec, both 20 mg once a day.  A lot of
>> people with stomach problem had their depression go away but stomach
>> problems return, and vice versa.
>
>Omeprazole (Prilosec) actually had another early name collision as
>well. For a while, the brand name was Losec. So why were the poor
>dyspeptics peeing like racehorces? Cause they were prescribed Losec,
>but given Lasix! When I was a senior scientist in the Drug Evaluations
>group at the AMA, my office was next to the person who managed the
>assigning of generic names. I discovered how close we were to a
>meltdown of the drug naming system, and that was five years ago!
>
>-Steven
>
>Name space is getting rather crowded.



   See, they wouldn't have these problems if they just left it called
nambumetone <g>.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: 27 Feb 1999 23:06:20 GMT

In <sbelknap-260219992243347148@dbts181.uicomp.uic.edu> "Steven
Belknap, M.D." <sbelknap@uic.edu> writes:

>>> It should be effective, though whether as good as indomethicin
>>> is hard to predict. And do remember, if you have problems, to take these
>>> things with Prilosec or other proton pump inhibitor-- it greatly cuts
>>> their stomach damaging proclivities (though maybe not to zero). I have
>>> the feeling that even the celebrated Celebrex is going to cause a few
>>> gut problems.
>>>
>>> 					Steve Harris, M.D.
>>
>> Soooooooo right!  I'm on Prilosec 20mg bid and Celebrex 200mg bid for RA
>> and it's STILL killing my stomach.  I'm going 2 days on, one day off for
>> now.
>>
>> Kitty
>
>You might try misoprostil 100 mcg with each dose of ibuprofen (400 to
>800 mg Q8, depending on the patient.) This is well tolerated by most
>people.


    Yes, though not as well as the proton pump inhibitors.  Gives em
diarrhea.  True in my own experience and true in the last studies.  And
not as protective, either.  Of course this is the average person, and
it makes sense to try something different for anyone who's have
problems with one regimen.

    As for Celebrex/celocoxib, I'm not impressed by what I read in the
Medical letter.   The have a 12 week endoscopy study 3200 pts total
which shows GI ulcer rate of 7% for celocoxib 200 bid, 10% diclofenac
75 (non slow release) bid, 35% Naprosyn 500 bid, and 23% ibuprofen 800
tid, and 4% placebo.   For something that supposedly doesn't inhibit
COX-1 at all therapeutic doses, they sure got a bigger ulcer rate than
placebo.  Is it worth paying $3 a day vs $2 to cut your ulcer risk from
10% to 7% ?

  In the 24 week study (2200 people) they got 4% ulcers with celcoxib
200 bid and 15% sustained release Voltarin/diclofenac 75 bid.    The
lesson, I suppose, is take diclofenac as the generic. Its lower ulcer
generally as a drug compared with the OTC standbys does correspond with
its partial COX-2 selectivity.  And there has to be a reason why they
didn't dare test Celebrex head to head against Relafen/nambumetone, the
most benign stuff on the market so far, and clearly the stuff to beat.

   And now for the ethics issue for today.  Why is it that the non
selective NSAIDS with the 20-30% chance of giving you an ulcer are OTC,
whereas the safer ones are all by Rx?  I thought the idea was for it to
be the other way around.  That's what the FDA *says* the purpose is.
Could they be fibbing?

                                         Steve Harris, M.D.

From: "Steven Belknap, M.D." <sbelknap@uic.edu>
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: Sat, 27 Feb 1999 21:43:47 -0600

> >You might try misoprostil 100 mcg with each dose of ibuprofen (400 to
> >800 mg Q8, depending on the patient.) This is well tolerated by most
> >people.
> >
> >-Steven
>
>     Yes, though not as well as the proton pump inhibitors.  Gives em
> diarrhea.

At a dose of 200 mcg 4X daily, misoprostil causes diarrhea or abdominal
cramping in about 1/3 of persons. At a dose of 100 mcg 3X daily, fewer
than 10% get diarrhea or cramps. I generally give the misoprostil with
each dose of NSAID, so if they are taking ibuprofen 800 Q8, they get
one dose of misoprostil with each dose of ibuprofen. Misoprostil also
protects against renal nephrotoxicity, which is a particular concern in
the elderly or those with atherosclerosis.

Both PPIs and misopristil are effective in reducing the rate of GI
upset. There have only been a very small number of studies with direct
comparison of these two drugs. At this point, it is still unsettled
which is better; it may depend on the relative doses being used and the
rate of adherence to the prescribed regimen.

>     As for Celebrex/celocoxib, I'm not impressed by what I read in the
> Medical letter.   The have a 12 week endoscopy study 3200 pts total
> which shows GI ulcer rate of 7% for celocoxib 200 bid, 10% diclofenac
> 75 (non slow release) bid, 35% Naprosyn 500 bid, and 23% ibuprofen 800
> tid, and 4% placebo.   For something that supposedly doesn't inhibit
> COX-1 at all therapeutic doses, they sure got a bigger ulcer rate than
> placebo.  Is it worth paying $3 a day vs $2 to cut your ulcer risk from
> 10% to 7% ?

Agreed. Also, they showed that it decreased the ulcer rate, but it
causes just as much GI upset, and so far there is no evidence it
decreases the gastrointestinal hemorrhage rate.

And in turn, why was nabumetone not compared directly with ibuprofen or
sulindac? It is unfortunate that independent clinical trials funding is
so difficult to come by. Incidently, in my clinical experience,
nabumetone causes about as much GI upset as ibuprofen.


>    And now for the ethics issue for today.  Why is it that the non
> selective NSAIDS with the 20-30% chance of giving you an ulcer are OTC,
> whereas the safer ones are all by Rx?  I thought the idea was for it to
> be the other way around.  That's what the FDA *says* the purpose is.
> Could they be fibbing?
>
>                                          Steve Harris, M.D.

In this case, the FDA is making the right call. Analgesic nephropathy
is the second most common cause of renal failure in the USA after
diabetes mellitus. We will need to have 5 years or so of experience
with celecoxib to know if it causes this problem. There are already
reports of (reversible) renal failure with celecoxib.

-Steven

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: 28 Feb 1999 11:26:51 GMT

In <sbelknap-270219992143478661@dbts183.uicomp.uic.edu> "Steven
Belknap, M.D." <sbelknap@uic.edu> writes:

>In this case, the FDA is making the right call. Analgesic nephropathy
>is the second most common cause of renal failure in the USA after
>diabetes mellitus. We will need to have 5 years or so of experience
>with celecoxib to know if it causes this problem. There are already
>reports of (reversible) renal failure with celecoxib.


   Since the vasodilatory properties of several prostaglandins help out
renal perfusion, we know that it would be truely weird if an "NSAID",
or at least an NSAID that worked by the traditional COX mechanism,
didn't cause some loss of GFR.  But it's reversible, as you point out.
And some of it will inevitably also be caused by selective COX-2
inhibitors, since brain and kidney are the few places where COX-2 is
present "constituitively" (ie, not induced by inflammation).  But this
is NOT the same mechanism as what produces "analgesic nephropathy" and
people on chronic dialysis forever.  That's a mixed bag which mix
almost always contains a ton of APAP (aka Tylenol), which is almost as
bad on the kidneys as the old outlawed phenacitin (which is metabolized
to the same active compound as APAP/acetaminophen-- so what do they
expect?)

   Analgesic nephropathy is the direct result of the DEA's deliberate
policy of using APAP as a denaturation agent for narcotics, in the same
way methanol was used to denature ethanol that wasn't meant to be
drunk, so that it could be sold without the imbiber's tax.  In the case
of APAP, if you take too much Darvon it just wrecks your kidneys.  The
DEA doesn't care.  It teaches a lesson to others.  Don't abuse drugs:
they can ruin your life.

   Check out codeine.  Put it with APAP and it's schedule III.  Same
dose without APAP (or indeed any dose of codeine alone) is schedule II,
and the level of control goes up sharply. The message could hardly be
clearer.  It's not that all that APAP makes it less likely to be
abused-- the stuff isn't antabuse, and it often doesn't make you sick
if you take too much chronically.  Until, of course, it's too late.

                                           Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: 1 Mar 1999 14:09:34 GMT

In <36D9D50C.ADD6F750@interlog.com> Happy Dog <happydog@interlog.com>
writes:

>"Steven B. Harris" wrote:
>
>>    Analgesic nephropathy is the direct result of the DEA's deliberate
>> policy of using APAP as a denaturation agent for narcotics, in the same
>> way methanol was used to denature ethanol that wasn't meant to be
>> drunk, so that it could be sold without the imbiber's tax.  In the case
>> of APAP, if you take too much Darvon it just wrecks your kidneys. The
>> DEA doesn't care.  It teaches a lesson to others.  Don't abuse drugs:
>> they can ruin your life.
>>
>>    Check out codeine.  Put it with APAP and it's schedule III.  Same
>> dose without APAP (or indeed any dose of codeine alone) is schedule II,
>> and the level of control goes up sharply. The message could hardly be
>> clearer.  It's not that all that APAP makes it less likely to be
>> abused-- the stuff isn't antabuse, and it often doesn't make you sick
>> if you take too much chronically.  Until, of course, it's too late.
>
>
>Is this why percodan & percocet contain analgesics?

   Why they contain aspirin or APAP.  Perhaps originally.  Today,
however, they're the same schedule as if they didn't.   It's only
codeine and "softer" narcotics which are allowed to be sold more
freely, if mixed with something toxic on overdose.



> In Canada, codeine
>cough syrup is sold sorta OTC.  (You have to ask the pharmacist.)  Not much
>codeine in it though...


    I'd be surprised if codeine was all that was in it.  That is never
true in the US.  The second ingredient always keeps you from drinking a
pint.

                                           Steve

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: 2 Mar 1999 02:12:26 GMT

In <36DAEC25.BA3D7E15@interlog.com> Happy Dog <happydog@interlog.com>
writes:

>"Steven B. Harris" wrote:
>
>>  In Canada, codeine cough syrup is sold sorta OTC.  (You have to ask the
>> pharmacist.)  Not much codeine in it though...
>>
>>     I'd be surprised if codeine was all that was in it.  That is never
>> true in the US.  The second ingredient always keeps you from drinking a
>> pint.
>
>Just looking at a bottle...  Eh voila: Each 5ml contains: 3.3mg of codine
>phosphate, 30mg of pseudoephedrine hydrochloride and 100mg of guiafenesin.
>Plus some inactive ingredients incl. alcohol.  The recommended dose is 10ml
>every 4hrs.
>hd



   Yep.  That much psuedofed will make you very dysphoric if you drink
a pint.  Might well make you hypertensive enough or a stroke, even.
And that much guaifenesin will make you very nauseated.

   So:  the codeine in your country is denatured also.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: Celebrex and Gout
Date: 3 Mar 1999 12:00:29 GMT

In <7bhlgv$h6f$1@nnrp1.dejanews.com> damonkarl@hotmail.com writes:

>In my opinion, if someone wants to get a nice codeine buzz, they're not
>really going to have too many problems.  Anyone with any background in simple
>chemistry can easily titrate the 8 mg of Codeine Phosphate out of the OTC
>pills called 222's in Canada.


   Anyone with a background in chemistry really doesn't have these
problems, in more ways than one.  But that's hardly an answer, since
most people don't.  "Well, Mr. Smith, it's easy.  Aspirin doesn't
disolve in cold water, but codeine phosphate does.  And separations
from other things are accomplished with titration of pH appropriately
to the pka of your narcotic, followed by solvent extraction.  Nothing
to it."   "Oh, I had no idea it was so easy, doctor."

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.pharmacy,sci.med
Subject: Re: APAP in Combo (was: Celebrex and Gout)
Date: 5 Mar 1999 13:11:34 GMT

In <7bo29u$2tl$1@nnrp1.dejanews.com> amp_spamfree@yahoo.com writes:

>Toxicity is one component of safety.  The greatest risk of pharmacologic
>misadventure is related to use patterns, not the drugs themselves. Drug
>interactions are more likely to result in adverse outcomes than drug
>toxicity.

   That being so, why would you want to make narcotics most easily
available in preparations where you cannot add another class of
analgesic without running into drug interaction?  Analgesic nephropathy
is generally a disease of people taking weak narcotics, NSAIDS, and
APAP all together.  It is the toxicity of the NSAID or APAP in the
fixed dose combinations which prompts people to add the third agent,
instead of simply increasing the dose of narcotic alone.  Pure agonist
narcotics alone are highly controlled.  In a previous message you said
something about codeine alone being an unusual and rarely used drug,
but you're confusing the cause and effect.  If it were schedule III
instead of schedule II, it would not used rarely at all.  Rather, it
would be used commonly when people hit the APAP or NSAID dose limit in
fixed dose combinations.  That pain relief limit, or wall, in schedule
III analgesics, is what sends people looking for something more at the
corner drugstore, when the doctor says "tough."   And lo, they usually
find it, since NSAIDS, APAP, and narcotics all have different
mechanisms of action, and are often synergistic.


>All drugs carry risks.	The best way to mediate the risk is to use the agents
>within the accepted use guidelines (I purposely avoid the term indications
>here for obvious reasons).  Promoting appropriate use results in better (and
>safer) outcomes.  One way to promote appropriate use is by limiting access -
>hence we have OTC and legend drugs, and within legend drugs we have scheduled
>and unscheduled.


    I can only comment that most things are safe when used within the
accepted use guidelines.  To use a non-pharmacologic example, the old
single shot revolvers were quite safe when used according to accepted
use guidelines (hammer down on empty chamber or fired brass).  Alas,
too many people screwed up to make the continued manufacture of such
arms a great idea, safety-wise.  So most have been converted if not
historical models (Ruger will do it free).  If the government was now
oddly insisting that we keep doing such a thing (making old style
single action revolvers without a transfer block or other adequate
safety), and had made it illegal to convert to the new style, you might
think that not only was the government not interested in safety, but
that it was actively trying to require use of a tricky product, in
order to teach people who misused it, a lesson.  It's hard to think of
why else they would do such a thing.   If the government makes codeine
harder to get then codeine mixed with tylenol, and makes it illegal to
separate the two, that tells you exactly what?  That the government is
so concerned about your pain ("Ah FEEL your pain...") that it mandates
the tylenol so you'll always have something extra with your codeine, in
case you forget?  No?  Then what?


>At least we agree that APAP and hepatotoxicity go together (as opposed to the
>Harris premise that nephrotoxicity is the main culprit).


   That depends on whether or not you're taking about acute or chronic
toxicity.   I will admit that it's usually not seen that people suffer
renal falure on the basis of narcotic and APAP alone, with nothing
else.   It's that tempation to add NSAID because you can't get rid of
the APAP and therefore can't increase the narcotic, that cause the
problem.  Or the temptation to add the APAP as a third agent because
you can't get rid of the NSAID in the fixed dose VIcoprofen and
therefore can't increase the narcotic.




> It takes quite a
>bit of APAP to cause irreversible hepatotoxicity - but I expect that some
>abusers could easily take their 20 grams in one sitting.  When it comes to
>drug dependency on prescription pain killers, codeine monotherapy is an
>unlikely candidate.

    The DEA disagrees with you, which is why it is schedule II.


> CII's of choice tend toward the dilaudids and morphines,
>not codeine.  I don't recall any combo's with these products to
>denature them.

    That's part of what makes them schedule II.  There are a few fixed
dose combo schedule II narcotics with ASA and APAP, to be sure (the
oxycodone ones) but only as monuments to frozen historical accidents.
These are basically once upon a time schedule III meds which got
upgraded because the potency of the narcotic was eventually found to
exceed the toxicity of the aduvant by too large a margin.  They chould
have cut the narcotic down.  Instead they simply upgraded the product
to another control classification.

   You seem to have some disdain of my explanation for why codeine
alone is schedule II, but codeine mixed with other things which do not
allow large doses to be taken, is schedule III.  I seem to sense in
your reply that you think codeine as a single agent is some kind of odd
epiphenomenon which nobody would want to abuse anyway.   I assure you,
it isn't.  Codeine is basically a prodrug for morphine, but has the
advantage of having a much better ratio of oral to paranteral efficacy,
and one that doesn't change over time.  But you think codeine alone is
a strange drug just because your rarely see it, and it doesn't prove
the point by itself?  Very well.  Explain to us then why tincture of
opium plus camphor (paragoric) is schedule III (or is it IV?), whereas
tincture of opium without the disgusting camphor (Laudenum) is schedule
II.  And why the benzodiazepine Librium is schedule IV, whereas the
fixed dose of Librium plus the nasty anticholinergic clinidium, in a
fixed combo known as Librax, is not a controlled substance *at all*?

   This should be interesting and creative.


                                        Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med,sci.med.pharmacy
Subject: Re: celebrex
Date: 24 Apr 1999 05:56:25 GMT

In <7fq156$kpq$3@bgtnsc02.worldnet.att.net> "mjdgdc"
<mjdgdc@worldnet.att.net> writes:

>The important point is the RELATIVE safety of Celebrex. The drug was
>introduced as a safer alternative to other NSAIDS, being a COX-2
>inhibitor and all that. If people are going to take an NSAID, the safest
>one is best (assuming the effectiveness is similar), and until further
>info disputes, Celebrex is still considered the safer alternative. For
>patients on blood thinners and in pain, Celebrex is a much welcomed
>arrival.
>
>Jon Garzillo DC



   Celebrex produced fewer stomach ulcers than diclofenac generic 75
bid and Relafen 750 bid, but the numbers were barely significant (7% vs
9% or something).  And these were asymptomatic ulcers seen on EGD:
nobody knows if they translate directly to serious ulcers causing large
bleeds (hospitalization needed) or death.  There were large differences
between Celebrex and the old propionic acid derviatives Naprosyn/Aleve
and Ibuprofen/Motrin, now OTC.  But that just means that the safer
NSAIDS are available only by prescription, not that Celebrex has yet
proven safe than the best of these.  FDA, take note.  We thought the
purpose of the prescription status was to keep access to the least safe
drugs more controlled?  Now we see that clearly corrupted by
profit-seeking.  We either need to get rid of the Rx status for drugs
(other than antibiotics or drugs that are addictive), or else get rid
of the laws which effectively allow a higher price to be charged for a
drug which is available only by Rx, rather than OTC (there is no
reason, for example, why an insurance company should not be able to
anounce that it will pay for drugs gotten by Rx, but which can be
bought OTC also).  Which status (OTC vs generic, by Rx vs. WITH Rx
ONLY, vs OTC), of course, need have nothing to do with patent vs.
generic status, which would still allow discovering companies to make
money to pay back their research costs and investors.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: barium enema vs colonoscopy
Date: 8 May 1999 09:19:12 GMT

In <3733B823.EA59208F@servtech.com> Ed Mathes <emathes@servtech.com>
writes:

>Final note.  There has been at least one recently published study that
>demonstrates that most guiac + stools have an upper GI source for the
>bleed.


 Sure enough.  I'm beginning to think the most important use of stool
guaiacs is to warn people that their NSAIDS are starting to erode their
GI tracts, and they need a Prilosec holiday.  Something like half as
many people die of NSAID GI bleed as from colon cancer, but years of
life lost?  It has to be closer.

  In any case, there is no doubt you must start with EGD first if you
scope.  And without melena, it's worth doing a month of Prilosec and
seeing where you are, even then.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.physics,sci.med
Subject: Re: Research Funding: (was jets and propellers)
Date: 17 Jul 1999 09:12:02 GMT

In <7molr2$4n$1@nnrp1.deja.com> pooua@aol.com writes:

>[snip]
>
>> >I remember a case like that in my neighborhood.  Old
>> >fellow collapses at street fair, but fortunately, doctor
>> >and nurse are standing right there! Perform CPR, revive
>> >gentleman, send him to hospital! Great heros! The local
>> >paper reported he died two weeks later in the hospital.
>> >Oh well.  At least a lot of income was transferred.
>
>I understand that an aspirin tablet administered to the
>victim during or soon after a heart attack would greatly
>increase victim survival rates.

   Only if his heart is still beating <g>.


>A half an aspirin tablet
>taken every day could significantly reduce the number of
>heart attacks.


   And significantly increase the number of severe GI bleeds and
probably hemorrhagic strokes (which tend to be those which cause the
worst long term morbility).  Whether or not total mortality would
change, even for just the group comprised of well-educated men 40 years
old and up, is not known.  This, because they stopped the longest and
best study of the matter (PHS) before they had data enough to decide
this.  For this we pay ethicists (sigh).  When I take aspirin, I don't
want to know, really, if it will prevent heart attacks.  What I want to
know is if it will improve my life.


> The down side is that aspirin causes
>physical damage to the stomach, so people are supposed
>to use coated aspirin.

    Which is not terribly important for low-dose aspirin, where the
small tablets are not very irritating (especially if a baby aspirin is
chewed), and the danger is produced not by local damage, but by having
platelets which don't work as well, in the face of other stomach
insults (ulcers from other causes, etc).  At high doses, BTW, coated
aspirin doesn't help much to protect the stomach either, since the
serious effect on the stomach there is the typical NSAID interruption
of COX-I mediated production of prostaglandins which control protective
stomach mucin production.  If it weren't so, all aspirin would be
coated and buffered by now.  Alas, years of trials show little effect
of these great sounding (but in practice not very helpful) ideas.

  Better advice is that people who take NSAIDS (aspirin, Aleve, Motrin,
etc) chronically would probably best also take a stomach acid blocker
also (Zantac, Tagament, Pepcid, etc. work okay, but the best ones are
still available only by prescription).


>Free medical advice; consider what you paid for it.


   Yep.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.physics,sci.med
Subject: Re: Research Funding: (was jets and propellers)
Date: 17 Jul 1999 13:33:37 GMT

In <37907467.F4063C3E@servtech.com> Edward Mathes
<emathes@servtech.com> writes:

>Steven B. Harris wrote:
>
>>  If it weren't so, all aspirin would be
>> coated and buffered by now.  Alas, years of trials show little effect
>> of these great sounding (but in practice not very helpful) ideas.
>
>Sure it's helpful!  A coated SA is easier to swallow dry than an uncoated
>one.  Same for coated Ibuprofen (advil).



Comment:

   Yes, and I'm sure that swords with handle-guards are easier to
manipulate when swallowing them, too.  The question is: why would you
want to?  If you need to take more than a baby aspirin where you can't
get to water, you probably should quit worrying about whatever it is
you're taking the NSAID for, and start worrying about water.  You
probably don't need the pills that badly.

>30-50% of NSAID users develop ulcers, a large percentage of
>which are asymptomatic.
>
>We had a severe GI bleed on Celebrex last month.


   Yep, the stuff is not totally benign in that way.  In the Celebrex
testing the company did for the FDA they found about 30% asymptomatic
GI ulcers on endoscopy for the standard OTC NSAID controls, and
something like 7% for Celebrex.  But the kicker is that they only found
something like 9% for Voltarin/diclofenac (semi-selective) and they
didn't test Relafen/nabumetone, which is my own favorite and probably
at least as good (and not likely as hepatotoxic).  And they surely
didn't compare Celebrex to [Relafen-or-Voltarin plus
Previcid-or-Prilosec.]  Which you can just about do at the prices they
charge for Celebrex.   You can certainly add OTC Zantac to nabumetone
or etodolac for the price they charge for the COX-2 inhibitors.  So why
no comparison studies?

   Blast the FDA, anyway.  The schmucks.  We have data that proton pump
inhibitors (PPI) are better at protecting stomachs than misoprostol (in
both efficacy and side effect), but here we have a combination
"Arthrotec" and no combination NSAID/PPI.  We have no OTC PPI, and no
good reason for *that* fact (the esophageal/gastric cancer risk has
turned out to be a confounder).  Nor do we have Relafen OTC.  So people
die of GI bleeds from OTC Aleve or Motrin at the rate of thousands a
year while your wise and watchful FDA dithers about a few cases of some
godawful rare and not very dangerous thing like-- pseudoporphria, or
something.  ARGGHH.

   I've already had one set of Celebrex hives/wheals in a lady who
forgot to tell us she had a sulfa allergy, and one case of GI
(intestinal) upset from somebody taking the new COX-2 drug just
recently out (name of which I don't remember, since I didn't prescribe
it).  As a class, I'm not yet very impressed.  No doubt they'll
improve.  Right now they still need lots of help, and to be used by
people with fear and trepidation.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.physics,sci.med
Subject: Re: Research Funding: (was jets and propellers)
Date: 18 Jul 1999 06:16:25 GMT

In
<chelp-1707991007440001@216-164-249-203.s457.tnt1.atn.pa.dialup.rcn.com
 chelp@my-dejanews.com (chelp) writes:

>In article <37907467.F4063C3E@servtech.com>, Edward Mathes
><emathes@servtech.com> wrote:
>
>> Also true.......30-50% of NSAID users develop ulcers, a large percentage of
>> which are asymptomatic.
>
>   Does H. pylori play any role in these ulcers?
>
>   Lisa


  In some fraction of them, yes.  But H. pylori is neither necessary
nor specific for people who get gastric ulcers taking NSAIDS.  It's
just a really bad risk factor.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.physics,sci.med
Subject: Re: Research Funding: (was jets and propellers)
Date: 18 Jul 1999 06:59:40 GMT

In <3790A6B3.66A5897C@servtech.com> Edward Mathes
<emathes@servtech.com> writes:

>chelp wrote:
>
>> In article <37907467.F4063C3E@servtech.com>, Edward Mathes
>> <emathes@servtech.com> wrote:
>>
>> > Also true.......30-50% of NSAID users develop ulcers, a large
>> > percentage of which are asymptomatic.
>>
>>    Does H. pylori play any role in these ulcers?
>
>Lisa, I recall a study that looked at that. I don't recall the result.
>
>I believe that there is no part played by H.pylori in NSAID induced
>gastric ulcers. Remember, HPylori is important in duodenal ulcers, being
>identified in 80% of cases. It is less important in gastric ulcers.


    Only because of NSAIDS.  If you exclude gastric ulcers caused by
NSAIDS, I suspect that H. pylori would be even more important than in
duodenal ulcers (which seem to have large stress and smoking
components).  In few human experiments self-ingesting H. pylori,
gastritis was all that was seen.

Newsgroups: sci.med.pharmacy
Subject: Re: Relafen question please
From: dyer@spdcc.com (Steve Dyer)
Date: Mon, 02 Oct 2000 04:59:55 GMT

In article <39D779F4.7892F6BE@houston.rr.com>,  <not-me@xyz.net> wrote:
> just been prescribed Relafen 750 mg X 1
> I was wondering ..is this similar to Vioxx or Celebrex ?? of which
>neither help me at all .. and is there any generic of any similar drug
>available for Relafen?
>The expense is going to keep me from using the 'real thing' :(

Relafen is closer in pharmacology to naproxen (Naprosyn, Aleve).
All NSAIDs exert their analgesic, anti-inflammatory and fever-lowering
effects by inhibiting the synthesis of prostaglandins, substances derived
from fatty acids that are involved in transmission of pain signals,
inflammation and fever.  They do this by inhibiting the enzyme,
cyclooxygenase (COX), which is involved in the synthesis of prostaglandins.

Now, it's been known for a long time that long-term chronic use of
NSAIDs can be associated with GI upset and even the development of
stomach and duodenal ulcers.  Some NSAIDs are worse than others
(indomethacin, ketorolac), and there's undoubtedly a good deal of
individual variability when it comes to an individual's susceptibility
to this side effect, but it's been observed in just about every NSAID.
It turns out that prostaglandins synthesized in the stomach help protect
against stomach acid, and by inhibiting their synthesis, you increase
the chance that the mucosa may be damaged.

It was recently found that there are several subtypes of cyclooxygenase:
COX-1 is more prevalent in the gut, whereas COX-2 is involved with pain
and inflammation.  Until this was appreciated, it wasn't possible to
design a drug that would preferentially inhibit COX-2, but spare COX-1,
and most NSAIDs inhibit both forms of the enzyme.  These newer COX-2
inhibitors, Vioxx and Celebrex, tend to have less of an effect on
prostaglandin synthesis in the stomach.  The inference from that is
that these drugs may be less likely to cause ulcers than the older
NSAIDs.

Like older NSAIDs such as ibuprofen and naproxen, Relafen acts as a
non-specific competitive inhibitor of all subtypes of COX (cyclooxygenase).
_However_, unlike most NSAIDs, Relafen is a pro-drug and is inactive by
itself; it has to be converted to its pharmacologically active metabolite,
a carboxylic acid similar to naproxen, in the liver.  This means that
there's less direct exposure in the stomach to a substance that can
directly inhibit prostaglandin biosynthesis (any exposure would be
systemic, after the drug was absorbed in the gut and metabolized by
the liver to its active form.)  So, the hope was that Relafen would
cause fewer ulcers than its fellow NSAIDs, though that's by a somewhat
different mechanism than the new COX-2 inhibitors.

Nonetheless, ulcers have been reported occasionally in certain people
taking Relafen, Vioxx or Celebrex, so the protection isn't absolute.

As far as I know, Relafen is still under patent protection, though
perhaps someone else can give you the details on when a generic form
might be able to be sold.
--
Steve Dyer
dyer@ursa-major.spdcc.com

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: NSAID Definition
Date: 6 Jan 2005 16:03:19 -0800
Message-ID: <1105056199.766052.45180@z14g2000cwz.googlegroups.com>

I don't think COX activity is necessary. Rimadyl/carprofen (a vet
arthritis drug) is generally considered a non-COX inhibiting NSAID. It
probably works higher up in the inflammatory pathway, at NF-kB or
something like that. Similar drugs are in the offing for human use, as
soon as the FDA gets it's head out.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: is there any alternate headache/paninkiller medicine fo NSAID
Date: 25 Aug 2005 11:51:25 -0700
Message-ID: <1124995885.138058.265470@g47g2000cwa.googlegroups.com>

Steven wrote:
> but she is allegry to medicine classified under NSAID.

COMMENT:

If she's had a reaction only to Ibuprofen (Motrin, etc) and Napoxen
(Aleve), that doesn't mean she's allergic to all NSAIDS. These are both
in the same class, and there are many other quite different chemical
NSAID classes. Nobody's allergic to ALL of them.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: misc.health.alternative,sci.med.nutrition,sci.med,alt.health,
	sci.life-extension
Subject: Re: Do You Hate Alternative Medicine?
Date: 31 Aug 2005 15:23:45 -0700
Message-ID: <1125527025.536437.49340@f14g2000cwb.googlegroups.com>

RArmant wrote:
> On 30 Aug 2005 21:16:46 -0700, Steve Harris
> <sbharris@ix.netcom.com> wrote:
>
> >Fish oil, with at least one good controlled trial, is on better ground.
> >But it needs to be used in far larger groups with a diversity of
> >problems before we know it's true relative place.
>
> NSAIDS as cox inhibitors can injure the stomach lining. Do you know what
> effect EPA/DHA has on the stomach -- in other words can fish oil produce
> stomach ulcers?


COMMENT:
No. If so, there'd be a lot of ulcerated Eskimos.  One reason I love
fish and borage oil, is they partly replace the most risky general use
drugs (prescription or not) in the medical armamentarium: NSAIDS. To
get more dangerous drugs you have to go to chemo, some heart drugs, and
the most powerful of the controlled substances. And NSAIDS, because
used so commonly, are still the champion pharmaceutical killers,
numbers-wise. They kill something like 20,000 people every year in the
US! That's a new 9/11 every couple of months! Their use remains an
embarrassment to the whole orthodox medical profession and pharm
industry, *unless* all the dietary tricks for modulating inflammation
more safely have been tried first. Even then, if you do the diet,
you'll need fewer NSAIDS.


> >Meanwhile, of course
> >I take it myself and give it to everybody I know :).
>
> For the record what is the dosage range that you recommend?

COMMENT:

You can start with 5 of the 1000 mg capsules of fishoil a day (about
1.5 grams EPA/DHA) and 2 of the 1000 mg capsules of borage oil (about
0.5 gram GLA). If you get a good anti-inflammatory effect, you can try
doubling this dose to see if you get anything more. All this can be
taken with any single meal.

It takes about 10 ordinary fishoil caps to equal a 7 oz salmon steak.
So this is not even pharmacological dosing. It's just few can eat that
much salmon every day, even if you could get farmed salmon that wasn't
full of arachadonate, or wild salmon that wasn't full of halogenated
industrial chemicals (PCBs and the stuff that pollutes the oceans more
and more). Since I have no way to guage all this, I take the
molecularly purified oil. Just buy the white "enteric" fishoil
concentrate pills from Costco (equivalent dose there is about 7 caps a
day, and twice the cost of the ordinary fishoil-- which is probably
still better than eating the fish).

The cheapest borage oil source I've found (which is the cheapest GLA
source) is Puritan's Pride.

SBH