From: ((Steven B. Harris))
Subject: Re: Arginine & Sexual Function
Date: 12 Jul 1995
Newsgroups: sci.life-extension

In <3tutpo$2td@crl6.crl.com> smart@crl.com (John Morgenthaler) writes:

>ARGININE & SEX
>(Nitric Oxide/Prosexual Hypothesis Validated)
>
>     New human studies on arginine and nitric oxide are confirming what
>laboratory animal and tissue studies have previously shown. L-arginine, taken
>orally, has a prosexual effect, probably resulting from an increase in the
>levels of nitric oxide (NO).



Yep, interesting.  I suggested doing this exact study to one of the
urology/sex/impotence researchers at UCLA about 3 days after the
connection between NO and erection hit the papers.  He agreed it would
be an interesting study, but wasn't too excited about it.  No drug
company was going to give him money to study arginine, I guess.

BTW, it also occurs to me that there is absolutely no reason, given
these studies, to imagine that arginine supplements should not also have
treatment value in mild cardiac angina-- the kind for which
nitroglycerine patches or nitrate pills are prescribed now.  It's all
the same mechanism.

                                             Steve Harris, M.D.

From: sbharris@ix.netcom.com (Steven B. Harris )
Subject: Re: Yohimbine, Minoxidil and  NO ...
Date: 09 Sep 1995
Newsgroups: sci.life-extension

In <suzmanDEIH5z.9DI@netcom.com> suzman@netcom.com (Peter Suzman)
writes:

>Peter H. Proctor (pproctor@sam.neosoft.com) wrote:
>
>> In article <41odha$1bg@citadel.evolving.com> Gregory
>> Bloom<gjb@evolving.com> writes:
>>
>> >pproctor@sam.neosoft.com (Peter H. Proctor) wrote:
>> >[snip-o-rama...]
>> >>     You bet...  Actually all of this is very tied in with life-extension.
>> >>Again to oversymplify:  Increased superoxide and its products seem to
>> >>be tied in with decreased longevity.  Nitric oxide and similar agents
>> >>( e.g., PBN ) seem to be associated with life-extension, as long as
>> >>you keep them away from superoxide.  We may be looking at just the
>> >>elephant's trunk.
>>
>> >Might an increased environmental NO concentration be beneficial?
>> >Perhaps a
>> >[snip]
>>
>> Actually, inhaled NO is used medically to treat pulmonary hypertension
>> ( in which there may be a deficit ).  The real problem is that NO is so
>> reactive that it has a blood half-life of a second or less.  This means
>> you can't use it directly as a drug except for lung problems.
>> 
>> The trick is to use NO analogs ( such as minoxidil ).  Or compounds
>> which release NO ( such as nitroglycerin, PBN, etc.). Nitroglycerin has
>> been used for 150 years or so, so this is not exactly new.  The problem
>> with such compounds is that they have to be metabolically-activated, so
>> you may not be able to get the NO when and where you want it.
>> 
>> Dr. P
>
>Some recent Medline cites posted on the migraine group claimed that
>either increased NO or hypersensitivity to NO was implicated in migraine.
>Giving migraineurs nitroglycerin typically provoked migraine-like
>headaches. This mechanism also could explain why MSG provokes migraines
>in some people. I've also heard reports of Minoxidil causing headaches,
>at least initially.
>
>So despite the other effects of increased NO, it could mean "Not tonight,
>dear, I've got a headache."
>
>Peter Suzman



   Right.  A good stiff snort or taste of nitroglycerin causes a
terrific headache in most people, not just migraine sufferers.  The
body adapts after time to that effect, or most people with coronary
disease would not be able to stand their nitrate treatment.  Years ago
(I heard this in medical school in the early 80s) cardiac patients
discovered that their nitroglycerin paste could be used directly on the
penis to give them erections (an early nitric oxide treatment as it now
appears), but if they didn't use a condom, the result was a really
terrific headache for the female partner.  No reports about whether the
[skull] "popper effect" (NO or nitrite vasodilation enhanced orgasm)
was consolation enough for this.  Timing here, I imagine, would be a
bit difficult.  It's not for nothing that poppers (alkyl nitrites) as
recreational drugs are sniffed.

                                              Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Viagra:  pharmacological mechanism?
Date: 19 Aug 1998 04:39:19 GMT

In <6rckg8$nk2$1@heliodor.xara.net> "Phil & Sue Morris"
<morriz@globalnet.co.uk> writes:

>Hi all,
>
>There's been an awful lot of hype, hysteria and humour about Viagra, but
>I still haven't seen an account of how this drug actually works in
>biochemical terms.
>
>Answers or references please!
>
>Phil
>Bath, UK



   Inhibits enzyme which breaks down cGMP, a second messanger in muscle
cells which vasodilate vessels in response to NO.  Effect is to
increase NO effect.  First tested as a blood pressure drug, but had
interesting side effects, as reported by first users.  Also, patients
refused to return their unused pills at end of study.  Company thought:
hmmmm.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Viagra:  pharmacological mechanism?
Date: 21 Aug 1998 00:43:08 GMT

In <35DB81D7.B0E1B576@servtech.com> Ed Mathes <emathes@servtech.com>
writes:
>
>Steven B. Harris wrote:
>
>>    Inhibits enzyme which breaks down cGMP, a second messanger in muscle
>> cells which vasodilate vessels in response to NO.  Effect is to
>> increase NO effect.  First tested as a blood pressure drug, but had
>> interesting side effects, as reported by first users.  Also, patients
>> refused to return their unused pills at end of study.  Company thought:
>> hmmmm.
>
> Isn't this an effect similar to amyl nitrate?  Poppers?


   It enhances the effects of nitrates and nitrites.  There have been a
few deaths in people using Viagra and poppers, and also heart patients
using Viagra and standard anti-anginal nitrates.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Viagra overdosing
Date: 27 Mar 1999 14:18:00 GMT

In <7dc0l2$omo@bgtnsc03.worldnet.att.net> "Mr. Joyboy" <"$.#"@#.$>
writes:

>So then Medboys, what's to be done with a overdose of Viagra?


   I would say immediate IV methylene blue, a treatment sometimes given
for met-hemogoblinemia.  But it is a little known fact that methylene
blue inhibits cGMP signal transduction, an overdose of which is the
problem with too much Viagra.  Of course, this is all theory.  Still,
methylene blue (which turns urine bright blue) is innocuous stuff (as
many a college prankster can testify).

   In the medical pipeline are various NO (nitric oxide) synthase
inhibitors and NO scavengers.  None are available commercially as
drugs, due to red tape wrapping of our lovely FDA.  All would be useful
in Viagra overdose.  There are a number of cheapy chemicals available
from Sigma which we use in dogs to keep blood pressure up in conditions
of NO overdose (from shock).  But if I gave such a thing to a person,
even somebody dying of hypotension from Viagra, they'd probably have my
license.  So in a standard medical setting it would be Levophed
(norepinephrine) and MAST trousers.

                                        Steve Harris

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: misc.consumers,misc.consumers.frugal-living,talk.politics.medicine,
	sci.med
Subject: Re: Disappointed and confused--don't know what to do
Date: 26 Apr 1999 00:24:03 GMT

In <7fvch2$pu2$8@ash.prod.itd.earthlink.net> kurtullman@sprintmail.com
(Kurt Ullman) writes:

>In article <7furhl$6gv@dfw-ixnews3.ix.netcom.com>,
>sbharris@ix.netcom.com(Steven B. Harris) wrote:
>
>>vitamin B12 and cure for pernicious anemia, the discovery of prion
>>brain disease and prions themselves, discovery of cancer-causing
>>viruses, the discovery of reverse transcriptase in viruses, discovery
>>of the genetic mechanism of mutation.  That sort of thing.
>>
>        Wasn't the last one for discovery of NO.. the paper headlined it as
>research that lead to the development of Viagra.. and oh BTW, it will probably
>have some heart related stuff, too)



   Yes, more than that.  Nitric oxide is the premier signal molecule of
vasodilation, inflammation, and the processes triggered by
inflammation, such as healing and immune activation.  It's why
nitrogylerine works, and nitroprusside.  It's a major mediator of
septic shock and reperfusion injury in tissues like the brain. It's in
the middle of most important pathogenic processes, somewhere.  It's a
tremendous discovery, and certainly deserved the Nobel.  Viagra is the
tip of one very big iceberg.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: soc.culture.indian,alt.fan.jai-maharaj,sci.med,soc.culture.usa,
	soc.culture.japan
Subject: Re: VIAGRA STUDY - MORE THAN ONE-THIRD DIED
Date: 18 Mar 2000 10:55:23 GMT

In <38CFF4ED.BECC3C78@nospam.com> jake <abc@nospam.com> writes:
>
>Bet you they had a smile on their face !!
>
>"Dr. Jai Maharaj" wrote:
>
>> VIAGRA RISK
>>
>> By Jessica Berman, in Washington
>> Correspondent Report 2-260197
>> Voice of America, via News Plus
>> http://www.mantra.com/newsplus
>>
>> Introduction
>>
>> An analysis of major side effects of the sexual
>> enhancement drug, Viagra, has been done.  And researchers
>> say that in more than one third of the cases studied,
>> patients died - usually of some sort of heart ailment.
>> As VOA Science Correspondent Jessica Berman reports, the
>> study's authors say the health risk to most men appears
>> very small but, for some men, the drug may pose an
>> unknown hazard.


   So, if you're at cardiovascular risk, it makes sense to get some
kind of stress test before you use Viagra.  Due to the nature of the
drug, I'd recommend a persantine-perfusion scan.  Viagra works
something like persantine, so if you survive the one without ischemia,
you should survive the other.

   I've suggested to the maker that it ought to test and market an IV
form of Viagra, to be used for chemical heart stress testing, in place
of persantine.  Basically, a Viagra-scan.  That would be the ultimate
screening test for men who worry if the phosphodiesterase-inhibitor
type vasodilators are safe.

   The drug company actually liked my suggestion, but I bet nothing
comes of it.  I mean, I recommended the hooker-stress-scan and the
mistress-stress-scan years ago, and it never caught on.  The FDA wanted
Phase I trials, and it was all a mess.

   What can I say?

                                        Doc Practicality

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med,sci.med.cardiology
Subject: Re: viagra
Date: Thu, 28 Feb 2002 10:05:59 -0800
Message-ID: <a5lrl0$b6r$1@slb5.atl.mindspring.net>

Carey Gregory wrote in message
<48ns7us7tprfb0q76t4je82s8bvdphjha8@4ax.com>...
><nlp-master@bk.ru> wrote:
>
>>Hello.
>>My name is Jim.
>>The following is a true story:
>
>Hi, Jim.  You're a spammer.
>
>My name is Carey.  The following is also a true strory.
>
>A local gentleman here ordered viagra by mail in preparation for his
>"big date."  Unfortunately, he died of sudden cardiac arrest... in
>bed... with his lover... before he was even able to get out of those
>elegant silk pajamas he'd purchased just for the occassion.  I felt
>really bad about having to slice them open up the front with a pair of
>shears.  They probably cost well over $100, but it didn't look like he
>was going to be needing them again.
>
>It was quite a scene... candle light, soft music, the half empty
>glasses of wine by the bed... his horrified, mortified lover in a
>sexy, sheer nightgown, crying and whimpering in the corner as a gaggle
>of paramedics feverishly tried to revive her lover.  Meanwhile, the
>neighbors all peered from their windows, wondering why all those
>flashing lights and police cars were in front of her house at 2am....
>
>It seems the poor gentleman didn't know viagra is an extremely
>dangerous, potentially lethal drug when combined with the other, very
>common medication he was taking.
>
>Alas, another viagra success story.


COMMENT:

Yep, Viagra can really stiffen you out sometimes, all right-- to do any
better, you have to go on with cryonics.

I've recommended to the Viagra people that they develop seldenafil as a
cardiac stress-test drug, much as persantin is used for that now. It puts
your ticker under load, but there's a lab and a bunch of docs watching you,
so it's a much safer proposition. It should work fine for the purpose, and
would be the perfect screen for people who are going to start using it as a
sex drug.

And you'd catch a lot of early and undiagnosed heart disease that way, as
well. It really is a crying shame the way the stuff is being promoted.  More
than half of men who have difficulty getting an erection have the problem
because they have beginning to develop atherosclerosis, and don't know it. I
know urologists convinced that this "sign" is a far more sensitive one and
more specific one than angina, and maybe as worrysome as a positive stress
test. New erectile dysfunction should trigger the full cardiac workup,
probably. Instead, it triggers some guy to go down to get a free sample of
something which his doc may not require him to get the screens for. Which he
generally uses for some strange and new woman that he's worried about
impressing (his wife already knows he sometimes can't perform), and the
combination of excitement and the new drug does him in.

Here we have the US surgeon general, whose job it is to tell the public such
important stuff. Like: "Hey, bub. If you think you might suddenly have the
need for Viagra, maybe it's time you got checked out for heart disease. See
your doctor."  Instead, we have TV commercials fueled by ungodly amounts of
pharmaceutical profits in which we have some guy who looks about 35 except
for the touch of Grey, putting on his necktie for that hot date (with the
wife <g>), hawking a molecules which is ACTUALLY going to be used by 50
year-old obese diabetic businessmen at some hardware convention, a thousand
miles from home where the wife still is.

I've thought about putting together a $1000-callgirl scan as a similar
screen for such men, but suspect that society isn't ready for that.  I think
you could save some lives that way rather pleasantly, but the insurers would
balk.

Say, have you heard there's another generic coming along in this same
family, called mycoxsadril?



SBH

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med,sci.med.cardiology,alt.support.impotence
Subject: Re: viagra
Date: Fri, 1 Mar 2002 17:39:55 -0800
Message-ID: <a5pafh$2n8$1@slb6.atl.mindspring.net>

sleazy@scummyISP.com wrote in message
<7ett7ukj0tflcsfivqojuf9jnhel7fld3s@4ax.com>...

>As to Dr. Harris, you shock me. I had you figured for one of the more
>helpful MD's around here, someone with a somewhat skeptical (OK,
>cynical) attitude towards the god-like affectations of the medical
>industry and their pharmacological supporters. Viagra is hardly one of
>the more obvious nor deserving targets.


Well, actually it is, but it's hard to know who to blame. We tolerate some
direct targeting of Rx drugs to consumers in the US, and the price we charge
for the information distortion this naturally causes, is to make the drug
companies do a bit of public service education at the same time. But it's
obvious that this kind of thing is not working as intended when our TV
commercials for birth control pills for women (for example) contain stuff
like "Birth control pills will not prevent HIV or sexually transmitted
diseases" (now there's a newsflash), as well as the heavier stuff like
"Women who smoke should not use the pill, or generally women over 40; and
possible side effects include clots in the lungs, stroke, heart attack
paralysis, death and have a nice day..."  While at the SAME time commercials
for Viagra have next to no warnings at all. And certainly don't mention the
important point that most impotence in men is connected to atherosclerosis,
and ought to make any man who is using erectile aid drugs think about having
a complete cardiovascular workup, if he hasn't already.  The FDA message
here is very clear: we don't see a woman who has a stroke while using an
oral contraceptive in the same political light as we see a man who has a
heart attack because he's in the wrong group to be using Viagra. We should,
however, because there is no difference.  I am merely recommending the same
sauce for the gander as for the goose, as it were.

>And you have some magic solution to atherosclerosis? Some other pill
>that makes the plaque disappear and the arteries become flexible?
>What's the point?

The point is that we're quite close to having just such stuff. Dying of a
big sudden MI in middle age in an affluent western country is now more a
matter of incredibly bad luck, really really bad genes, or shear stupidity--
sort of like losing all of your teeth in this modern age of dentistry and
periodontics. Atherosclerosis is not like metastasized pancreatic cancer--
it's in general now a very treatable problem. With smoking cessation, proper
diet, and drug treatment most people can now put their coronary risk factors
exactly where you want them. You can also take aspirin and other
preventives, as well as get a stress test (and angiography and even surgery
if necessary) to give them some idea of how much time and room you have to
deal with the problem, and/or give them the time if they need it. Under such
conditions atherosclerotic lesions DO stop growing, and often actually
regress.  Proper treatment makes a tremendous difference in risk of future
MI. There are no guarantees yet, and regression doesn't happen immediately,
of course. But it's quite common to see studies in which risk of future MI
in treatment groups is cut to a tiny fraction of placebo; and I've no doubt
the odds are higher yet for combinations of treatments with regard to no
treatment (which is what you get if you ignore warnings like impotence).
They don't do such studies because with what we know by now about treatment
of atherosclerosis, they'd be immoral.  In any case, you see the point. This
is something you want to know about. As you pelvic arteries now, so go your
coronary arteries tomorrow.


>No doubt Pfizer is making a bundle off Viagra at a non-insurance-
>reimbursed (mostly) $10 per 100mg but I say thank god for Pfizer and
>for Bob Dole. They should get the nobel prize! Even apart from the
>medical effects of Viagra, the wonder drug, they deserve credit for
>taking impotence our of the shadowy world and establishing it as a
>condition to be treated and researched just the same as--oh, let's
>say--asthma, or at least acne.

The point is that Viagra doesn't treat the problem, which is (too often)
pelvic atherosclerosis. It treats the SYMPTOM. Sometimes the only symptom
some of these men will have for years-- until they get the big MI.

If somebody had just discovered nitroglycerin pills, and the company had Bob
Dole come on TV and say: "Say, men, do you get chest pain sometimes when
shoveling snow?  Try a bottle of THESE.  They work for me when MY chest
hurts during exercise."  Then you'd get it.  Wouldn't you?

This is not to say that nitroglycerin pills are not a good thing. They are.
When used by people who know what they're doing. But if some company should
really try to market nitrates that way to people with the "problem" of chest
pain, like the problem of impotence, the FDA would go bananas.  They don't
think about Viagra the same way. They probably should.

SBH

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med,sci.med.cardiology,alt.support.impotence
Subject: Re: viagra
Date: Sat, 2 Mar 2002 15:42:53 -0800
Message-ID: <a5ro05$t99$1@nntp9.atl.mindspring.net>

Jerry Sturdivant wrote in message <01c1c1fc$0d631080$LocalHost@jerrys>...
>
>Steve Harris <sbharris@ix.RETICULATEDOBJECTcom.com> wrote
>
>> The point is that Viagra doesn't treat the problem, which is (too
>> often) pelvic atherosclerosis. It treats the SYMPTOM. Sometimes
>> the only symptom some of these men will have for years until
>> they get the big MI.
>
>Doesn't this become a moral call? You take some old fellow that's lead a
>sedimentary life style. Enjoyed all life's had to offer. Lived in the
>buffet line. Smoked. Generally lived for quality of life, not quantity.
>
>Give him the facts and the odds; tell him he needs a physical and let him
>make the decision. If the blood-pressure lowering pills may conflict with
>Viagra, offer the option of trimix penile injections. There's no law
>against endangering your life in the seeking of pleasure.


Of course I have no objection if it's done this way. But it's not. You see
the young guy on the Viagra ads, who can't be more than about 40 and isn't 5
lbs overweight, and you might get the idea that impotence is just something
that naturally happens to large fraction of men as a result of being over
35.  No big deal. Nothing to get embarrassed or even worried about. Doesn't
mean you're sick. Just see your doctor and get the fix pill.

Well, it is something to worry about. And it may well mean that you're sick
as hell, and in fact you're (technically) dying. You're no younger than your
arteries, and some of your better arteries are complaining. And sure, you
can take the Viagra and ignore all this. Great.  Just so you don't say we
didn't tell you.

SBH