From: sbharris@ix.netcom.com (Steven B. Harris )
Subject: Re: Parke-Davis quit making oral chloramphenicol.  Who does?
Date: 13 Sep 1995
Newsgroups: sci.med,sci.med.pharmacy

In <435hdd$5e5@ixnews3.ix.netcom.com> chicago@ix.netcom.com (Chicago)
writes:

>Parke-Davis informed me that they quit making chloramphenicol in its
>oral form about a year ago, and now only make the IV preparation.  I
>need oral chloramphenicol for a case involving antibiotic resistance.
>Does anyone know where in the world the oral form of chloramphenicol is
>still manufactured?  And how good its quality is?
>The explanation Parke-Davis gave for only manufacturing IV despite oral
>apparently achieving higher levels is that now its major use is in the
>hospital setting for pediatric cases.
>Brad H, MD



Well, I'm sure you can get it in Mexico.  As you know, the problem with
this drug is that it kills a few people out of every 100,000 or so,
with bone marrow problems.  The oral form and eyedrop forms, for some
reason, are more associated with this (it's rare IV, and may have to do
with some strange gut metabolite).  In any case, generally this means
it's not recommended for anything but life-threatening illness-- for
which you'd probably have someone in the hospital anyway.  What are you
treating, out of curiosity?

   Supposedly there is a derivitive drug called methamphenicol which is
much less likely to cause the bone marrow problems.  But it's not
available in the US.  A shame.


                                           Steve Harris, M.D.

From: sbharris@ix.netcom.com (Steven B. Harris )
Subject: Re: Parke-Davis quit making oral chloramphenicol.  Who does?
Date: 13 Sep 1995
Newsgroups: sci.med,sci.med.pharmacy

In <435hs3$q9q@ixnews2.ix.netcom.com> shelbyb@ix.netcom.com (Harold
Boxenbaum ) writes:

>In <435hdd$5e5@ixnews3.ix.netcom.com> chicago@ix.netcom.com (Chicago)
>writes:
>
>>Parke-Davis informed me that they quit making chloramphenicol in its
>>oral form about a year ago, and now only make the IV preparation.  I
>>need oral chloramphenicol for a case involving antibiotic resistance.
>>
>>Does anyone know where in the world the oral form of chloramphenicol is
>>still manufactured?  And how good its quality is?
>>The explanation Parke-Davis gave for only manufacturing IV despite oral
>>apparently achieving higher levels is that now its major use is in the
>>hospital setting for pediatric cases.
>>Brad H, MD
>
>
>The injectable can be taken orally, although it might taste bad. Also,
>are there generics?  Veterinarians use this routinely, since the
>toxicity seen in humans does not exist in animals.  Contact one of your
>local veterinarians.  I'm sure the quality would be OK.
>
>Harold.


  Yep.  That's a general rule for all drugs, BTW, although it makes
pharmacists cringe.  Just about all IV preparations of orally absorbed
drugs can if necessary be given orally.  I think dilantin is an
exception, due to the very odd pH of the IV preparation.  But if you
put it in juice you'd again probably be okay.

                                              Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Subject: Re: Virus Immunology; a general viricide
Date: 20 Apr 1997
Newsgroups: sci.med.radiology,sci.bio.technology,sci.bio.misc,sci.med,
	sci.bio.microbiology

In <1997042008482417209@yellow-gre2-163.wanadoo.fr>
Jean.Pelmont@wanadoo.fr (J.R. Pelmont) writes:

>2) AZT : the HIV is a retrovirus, is can be replicated by using a
>reverse transcriptase, an enzyme converting virus RNA into double
>strand-DNA. AZT is converted to an analog of one of the true substrates
>of the transcriptase, disrupting DNA synthesis. Normal cells do not make
>their DNA using such an enzyme, and are not bothered too much (it is
>hoped :there are some side efects).
>
>Very often the selectivity of various drug is not that clearcut. For
>instance chloramphenicol, a well-known antibiotic for external use,
>prevents the growth of bacteria by knocking down their protein
>synthesis. In plant and animal cells, the bulk of protein synthesis is
>insensitive to chloramphenicol, because the targets are the ribosome
>particles, that are slightly different in that case. But chloramphenicol
>still bothers protein synthesis in mitochondria, because their machinery
>is of the procaryotic type. This is one of the reasons why
>chloramphenicol is a fairly toxic antibiotic.



    Mitochondria, because they decended from bacteria and still retain
some bacteria-like machinery, are a real problem this way.  Another
problem is that mitochondrial DNA synthetic enzymes aren't very
sophisticated, and end up getting nailed by antivirals.  A few years
ago an experimental drug for hepatitis B killed all the mitochondria in
half a dozen patients' livers, causing them to need transplants (a
couple died anyway).  And a main AZT side effect is damage to muscle
mitochondria in this way.  Other AIDS antivirals kill nerve
mitochondria, causing neuropathy.

    Chloramphenicol, besides the straightforward toxicity to
mitochondria, has another kind of toxicity which is very bizarre.  It
causes loss of bone marrow and death from aplastic anemia, and it isn't
dose dependent.  Susceptible people can die months later from a couple
of eyedrops containing the drug.  Go figure.  Perhaps some kind of
triggering of an autoimmune reaction which then goes on to kill you,
long after the drug is gone?  Luckily, it's rare.

                                        Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: misc.kids.health,sci.med,misc.health.alternative
Subject: Re: Kipper Harris
Date: 9 Feb 2000 03:04:20 GMT

In <87p8am$t4g$1@pegasus.csx.cam.ac.uk> "Bennett" <njb35@spam.ac.uk>
writes:
>
>
>John <whale@whaleto.freeserve.co.uk> wrote in message
>news:87olrs$u82$1@newsg3.svr.pol.co.uk...
>>
>> Have you a list of people who got aids and never took drugs (rec or
>> pharm), vaccines or a blood transfusion?
>
>Ascher et al, Nature 1993 Mar 11;362(6416):103-4, for one example.


   Alas, not an example if you demand absolutely NO drug use.  Asher's
"no drugs" group was actually a "low use" group defined by less than a
certain number of uses per time period.  I don't think they could find
a large group of honest HIV infected gay men in San Francisco who never
ever used any illegal drug ever.  Such a study might be possible if you
look hard enough and long enough, but it would be pointless all the
same.  If drugs cause AIDS, and do so for the reason that Duesberg says
(large amounts overwhelm the immune system) then there should be a
really strong dose effect.  The point of the Asher study is that there
isn't.

   It's rather hard to convict a drug of causing a problem without a
dose effect and it's only been done successfully in one case that I
know of (chloramphenicol).  If one cigarette a day smokers had the same
increased lung cancer risk as 3 pack a day smokers, we'd be arguing
over that causal connection even yet. And if chloramphenicol was a
recreational drug, the skeptics would be having a field day now about
the risks of that.  But with a low risk and no reason for people to lie
themselves about the risk that exists, there's no major skeptical
movement for that.

From: sbharris@ix.netcom.com (Steve Harris  sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.pharmacy,sci.med,sci.chem
Subject: Re: What is phenazone (antipyrine) ?
Date: 9 Oct 2003 14:15:25 -0700
Message-ID: <79cf0a8.0310091315.39d8e87a@posting.google.com>

Buckleys <the_buckleys@optusnet.com.au> wrote in message
news:<3F8575EB.A1C@optusnet.com.au>...

> Steve Harris sbharris@ROMAN9.netcom.com wrote:
> >
> > hillary@hillary.net (Hillary Israeli) wrote in message
> > news:<slrnbo6ngg.f3m.hillary@manx.misty.com>...
> >
> > > In <79cf0a8.0310051934.2c5400e8@posting.google.com>,
> > > Steve Harris  sbharris@ROMAN9.netcom.com <sbharris@ix.netcom.com> wrote:
> > >
> > > *This is an old fever/pain drug which is chemically a pyrazolone. Not
> > > *really like anything else I know of. There is no strict US equivalent
> > > *as the drug was long ago taken off the market here because it
> > > *occasionally caused agranulocytosis (no white cells in the blood).
> > >
> > > What's up with the Norwegians and Finns using drugs that cause this type
> > > of problem?
> > >
> > > I was pretty shocked when our last au pair, from Finland, arrived bearing
> > > a bottle of chloramphenicol eyedrops.
> >
> > COMMENT
> >
> > ROFL! Good pickup. That's pretty bad. Can Swedish Methotrexate Vapor
> > Rub be far behind?
>
> Does topical chloramphenicol cause amaemia too? I didn't think it did -
> it is still prescribed for eye infections in Australia AFAIK, but not
> for internal use.



The aplastic anemia very rarely and idiosyncratically caused by
chloramphenical is NOT dose-dependent. Which means it's probably some
kind of weird allergy-like autoimmune thing, and not a straightforward
toxicity at all. And yes, eyedrops (of which some is always absorbed)
have been reported to cause it. Thus, the drug is only used for
life-threatening conditions (meningitis), and should NEVER be used in
human eyedrops (where by definition it's being used for some non-life
threatening problem).

Oddly, there is an analog of chloramphenical called methamphenical
which has similar antibacterial properties but no history of causing
this aplastic anemia. However, it's never been approved in the US.
That's the old generic money problem again. So we remain stuck with
chloro.