Tastes Like Chicken, " wise beyond his years ", gg, as they say, GG.Thus, definitely no need for Viagra so far. Still marching on natural endowments.what can I say, TLC....
But I digress.If you should [miraculously]see Carroll again with the blond, please tell him not to drink grapefruit juice or red wine or take Zithropac, ( an Erythromycin) with Viagra .
Re: Further medical info on Viagra, not included in patient package insert,
TA
{PS Skip first section on rape. We will assume Carroll didn't rape the blond }.
Message 4758275
To: DaiS (9290 )
From: Zebra 365 Sunday, Jun 7 1998 2:11PM ET
Reply # 9292of 9325
<<We have had the suspected viagra deaths but no VIAGRA RAPES yet I think - I find this strange. Given that viagra increases the frequency and level of desire as well as sustaining performance, the possibilities are horrendous.>>
DaiS
There is a common misconception about rape. The perception is that it is a violent expression of sexual desire. I'm certainly no expert but having spent some years as the director of an Emergency room and dealing with the aftermath, I can say that this is not the case in at least 95% of rapes.
Rape is a sexual form of violence. Many cases of rape are difficult to prosecute because there is no ejaculation and therefore no genetic proof of the rape. Much as a rattlesnake that bites a large animal (always in fear for its life) very often injects no venom; the rapist often does not derive sexual pleasure from the act.
Most of the victims of rape are not attractive young women, and often it happens to elderly women. Also, I've seen no published evidence that Viagra or any ED treatment increases sexual desire.
Another poster (Sal) asked about the "grapefruit effect in Viagra".
<<How will grapefruit juice affect a man who uses Viagra?>>
Many drugs are deactivated in the liver. In this case think of the liver as a factory in reverse (like a "chop shop" for stolen cars), it disassembles Sildenafil (Viagra) molecules into another molecule (which still has some effect, 50%) and then disassembles that molecule into something that has no effect (that is then eliminated in the urine (13%) or feces (80%).
Sildenafil has a half-life of about 4 hours in healthy young volunteers, that means this process eliminates 50% of the drug in 4 hours (and 25% in the next four hours, and 12.5% in the next four hours) Theoretically after 12 hours you would still have 12.5% of the drug in your system, and it would be effectively gone after 24 hours (six half lives). Healthy elderly (>65) volunteers cleared sildenafil less than the younger ones, resulting in plasma levels 40% higher at the same dose.
In someone drinking grapefruit juice or eating a grapefruit, this factory line could be as much as 90% shut down. This could increase the half-life by ten-fold, i.e. a factory working at 10% capacity takes 10 times as long to produce as much.
If this then extended the half-life by 10-fold it would become forty hours instead of four just to eliminate half the drug, then the dose you take on Tuesday is still mostly around when you take a dose on Wednesday and has additive effect. (PFE recommends no more than one dose per 24 hour period.)
As side effects increased with dosage in the reported studies (plasma levels) this would likely increase the side-effects (and desired effects) of the drug. Exactly to what extent I cannot say. As I mentioned, this grapefruit effect on this enzyme system, has only recently been discovered and is now being studied.
Most drugs known to use this enzyme system are now having grapefruit warnings added to their label material. PFE warns about ketoconazole type drugs and other "inhibitors of these isoenzymes" with Viagra but did not mention grapefruit in the initial package insert.
They did try giving 100 mg of Viagra each day to someone at the same time that person was taking a normal dose of erythromycin. This resulted in sildenafil buildup to 182% higher levels than without the Erythromycin. Erythromycin is nowhere near as powerful an inhibitor of this enzyme system as grapefruit.
Tagamet (800mg) given with a single 50mg dose of Viagra, caused a 56% increase in plasma concentration of Viagra in healthy volunteers (age not given)
Elderly people already have reduced activity of this system, if you couple that with an AM grapefruit, and that dose of Viagra, you see my point?
My main point is that people often think of drug-drug interactions but often little attention is given to drug-food interactions. The grapefruit effect on certain drugs is one of the more important drug-food interactions yet discovered.
I suspect PFE will add it to the label material soon. With all the hype that Viagra gets, it would be an excellent chance to increase general awareness (among both physicians and patients) of this newly discovered grapefruit interaction.
(Now I'm probably kicked off the mailing list for the Texas Ruby Red Grapefruit people. I love those, have some in the fridge right now and send them for Xmas gifts. See why I have to use a pseudonym!)
Zebra
P.S. I do not think this applies to all citrus fruit, only grapefruit as far as has been reported. And red wine to a lesser extent.
Message 4758361
To: Sal Milani (9291 )
From: Zebra 365 Sunday, Jun 7 1998 2:21PM ET
Reply 9294 of 9325
More about the grapefruit effect on Viagra....
Life Sci 1998;62(10):PL135-PL142
Mechanism-based inactivation of human cytochrome P450 3A4 by grapefruit juice and red wine.
Chan WK, Nguyen LT, Miller VP, Harris RZ
Department of Pharmaceutics and Medicinal Chemistry, School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA. wchan2@uop.edu
Grapefruit juice is well documented to cause clinically significant increases in the plasma concentrations of many therapeutic agents. These interactions are believed to be mediated via inhibition of intestinal cytochrome P-450 3A4 (CYP3A4) by flavonoids and/or other chemicals in grapefruit juice, although the mechanism of that inhibition has not been fully characterized. Like grapefruit juice, red wine contains large amounts of flavonoids and other xenobiotics which could also mediate CYP3A4 inhibition. In this study, we investigated the mechanism of inhibition of CYP3A4 by grapefruit juice and also examined the ability of red wine to inhibit this enzyme. Both red wine and grapefruit juice potently inhibited CYP3A4 activity in a concentration-dependent manner. At 8% of natural strength, enzyme activity was inhibited almost 90 and 84%, respectively, by grapefruit juice and red wine. In contrast, white wine did not appreciably inhibit CYP3A4 activity. Grapefruit juice irreversibly inactivated CYP3A4 in a time- and NADPH-dependent manner. The rate of inactivation mediated by grapefruit juice was similar to that mediated by troleandomycin, a potent mechanism-based inhibitor of CYP3A4. Red wine also inactivated CYP3A4 but at a rate approximately 16% that of grapefruit juice. Inhibition of CYP3A4 by red wine is primarily reversible in nature. The clinical implications of this research are discussed.
I guess Viagra is like fish, only goes with white wine.
Seriously, some of those sexy seniors are also drinking lots of fruit juices and taking bioflavinoid supplements for their atherosclerotic prevention. This study suggests that the Cyt P450 (CYP3A4) is inhibited 90% by grapefruit juice with only 8% real grapefruit juice (common in commercial fruit drinks to be only about 10% real juice.) A friend of mine is a cardiologist who is very big on flavenoids, I always know when he has referred a patient to me, because they are all taking the bioflavinoids (look in your supermarket vitamin section, flavinoid supplements are available without a prescription) And now of course, we have the atherosclerotic patient as a prime target market for Viagra.
Zebra |
