Posted by michael on November 8, 2000, at 22:24:34
In reply to Re: Need Some Drug Advice » JohnL, posted by michael on November 8, 2000, at 21:56:56
sorry - it's spelled ondansetron - here's a quick blurb (hope it's not too long):
Description: Ondansetron is an oral and parenteral antiemetic agent. It is the first selective serotonin blocking agent to be marketed. It is similar to granisetron, which was marketed in 1994. Ondansetron is an extremely safe and highly effective antiemetic that has greatly improved the ability to give chemotherapy. The quality of life of patients has been tremendously better with ondansetron than with older, traditional antiemetics. When administered at optimal doses, ondansetron and other selective serotonin antagonists (e.g., granisetron) are equally effective. Ondansetron has occasionally been utilized for the treatment of hyperemesis gravidarum refractory to other treatments. Novel investigational uses of ondansetron include treatment of gastrointestinal motility disorders and drug dependence. Ondansetron was originally approved for the treatment of chemotherapy-induced nausea/vomiting by the FDA in January 1991 and oral dosage forms were approved for the treatment of post-operative nausea/vomiting in April 1995. An orally disentegrating tablet, Zofran ODT®, does not require water to aid in swallowing, and was approved by the FDA in February 1999.
Mechanism of Action: Ondansetron may have central and/or peripheral action. Ondansetron preferentially blocks the serotonin 5-HT3 receptors. 5-HT3 receptors are found centrally in the chemoreceptor trigger zone and peripherally at vagal nerve terminals in the intestines. Whether the action of ondansetron is mediated centrally, peripherally, or a combination of both remains to be determined. Emesis during chemotherapy and radiation therapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine. Blocking these nerve endings in the intestines prevents signals to the central nervous system. Ondansetron is also a weak antagonist of the 5-HT4 receptor, and may bind to other serotonin receptors as well. Ondansetron has also been demonstrated to bind to the opioid µ receptor. The clinical implications of these actions is uncertain. Ondansetron has no dopamine-receptor blocking activity. Colonic transit time is slowed after multiple oral doses of ondansetron.
Pharmacokinetics: Ondansetron is administered orally and parenterally. Oral bioavailability of the tablets is 59%. The drug is also administered by IV infusion. Animal studies indicate that ondansetron has no teratogenic effects and that it is distributed into breast milk. Approximately 36% of an ondansetron dose is distributed into erythrocytes. The drug is about 7076% bound to plasma protein. Ondansetron undergoes extensive metabolism, mainly by hydroxylation, followed by glucuronide or sulfate conjugation. For adults, the mean elimination half-life is 4 hours; patients under age 15 years show a shorter half-life of about 2.4 hours. Less than 5% of an intravenous dose is eliminated unchanged in the urine. The inactive metabolites are eliminated in the urine.
and granisetron:
Description: Granisetron is an oral and parenteral antiemetic agent. It is commonly used to offset nausea and vomiting from highly emetogenic cancer chemotherapy and its efficacy has recently been demonstrated in combination with dexamethasone.[572] Granisetron is similar to ondansetron in activity, efficacy, and adverse effects. Unlike ondansetron, it is not approved for postoperative emesis. Despite its effectiveness, granisetron is not recommended for the routine treatment of nausea due to its significant cost relative to other anti-nauseants. Granisetron injection was approved by the FDA on December 29, 1993. The oral dosage form was subsequently approved March 20, 1995 and has been shown to be as effective as IV ondansetron for chemotherapy-induced nausea and vomiting. In July 1999, the FDA approved granisetron for the prevention of radiation induced nausea and vomiting.
Mechanism of Action: Granisetron may have central and peripheral actions. Granisetron selectively blocks type 3 serotonin (5-HT3) receptors. 5-HT3 receptors are found centrally in the chemoreceptor trigger zone and peripherally at vagal nerve terminals in the intestines. Whether the action of granisetron is mediated centrally, peripherally, or a combination of both remains to be determined. Its affinity for 5-HT3 receptors is 4,00040,000 times higher than for other serotonin receptors.[488] Emesis during chemotherapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine. Blocking these nerve endings in the intestines prevents signals to the central nervous system. Granisetron may antagonize the effects of serotonin on the cholinergic neurons of the colon, slowing colonic transit time.
Pharmacokinetics: Granisetron is administered orally and parenterally. The pharmacokinetics of granisetron are similar in pediatric and adult cancer patients when the volume of distribution and total clearance are adjusted for body weight. Granisetron distributes freely between plasma and erythrocytes. Coadministration with food decreases the AUC by about 5% and increases the Cmax by about 30% in nonfasted healthy volunteers. It is unknown whether granisetron crosses the placenta or is distributed into breast milk, but animal studies have revealed no teratogenic effects. Approximately 65% of the drug is protein bound.
Granisetron undergoes N-demethylation and oxidation in the liver. Because in vitro studies have shown that the primary route of metabolism of granisetron is inhibited by ketoconazole, the cytochrome P-450 system is probably a metabolic pathway of the drug. Animal studies indicate that the metabolites may have pharmacologic activity. The terminal half-life following IV administration is 912 hours in cancer patients and 57.7 hours in healthy individuals. Oral administration results in a half-life of 6.23 hours in normal volunteers; no data is available for the oral half-life in cancer patients. There is considerable interpatient variability in the clearance. Approximately 12% of a dose is eliminated unchanged in the urine. The metabolites are excreted in the urine (49%) and the feces (34%). Dosage adjustment in patients with renal or hepatic disease is not necessary.> Hey John,
>
> The last piece of the puzzle...
>
> For what it's worth - as I've mentioned before - bromocriptine seemed to help with that. I think 5mg once or twice a day, seemed to take effect pretty quickly... (got the idea from the "tips" section)
>
> I also noted that in the "tips" section, one doctor mentioned granisetron, a 5HT3 antagonsist was helpful - however, it's very expensive. (I think it's to treat nauseau (sp?))
>
> In the same vein, perhaps odansetron, which I think is similar, might be an option. (kind of guessing here, haven't done any research on this lately) I believe andrew mention it a while ago, and that it had mildly mentally energizing effect...? I think that it too is generally really expensive, but it can be found abroad for a fairly reasonable/inexpensive price.
>
> Those are my best ideas. Tried yohimbe - the otc stuff. It was definitely helpful for that particular symptom/side effect, but was accompanied by a really "edgy" feeling...
>
> Good luck, and I hope you'll pass along the "right" answer when you determine what it is!
> michael
>
>
> > I need some help from my drug expert buddies out there.
> >
> > As everyone knows, I've done extremely well with low doses of Amisulpride+Adrafinil. I have one and only one side effect. But it's a bad one. Impotence.
> >
> > My pdoc retired. My GP moved away. Out in the cold, I had to find a new doc. I found one. I spent no time researching, I just sought the GP nearest to where I live. As it turns out, I got lucky, he's awesome. We discussed everything in detail, but still I need feedback from folks here at this board.
> >
> > His first suggestion was to try Viagra. I didn't like Viagra, but may have to revisit that option if all else fails.
> >
> > His second suggestion was to try me on one week of extended release Ritalin instead of Adrafinil, and then one week of Adderall. I couldn't believe it! Has this guy been reading Jensen stuff, or what?
> >
> > If these trials don't turn out well for whatever reason, then next he would have me restart the Adrafinil, and possibly try an alpha-1 antagonist to counteract it on an as-needed basis. I think he mentioned Prazosin. This maybe in combination with Viagra.
> >
> > In the end, if all these things fail, then he would have me consider longterm trial of Wellbutrin in addition to my other drugs.
> >
> > My question to you all is this...Do you think an alpha-1 antagonist like Prazosin could counteract the agonist activity of Adrafinil? I read one clinical study where Prazosin did do that to Provigil. But I also wonder if that is something that could happen right away, or whether it is something that would take time. I mean, Adrafinil takes time to work. From what I've read about Prazosin, it takes time too. I wonder if it would have any effect on an as-needed basis.
> >
> > I also noticed there is a drug called Nicergoline that is also an alpha-1 antagonist which is supposedly much more competitively powerful in site binding than Prazosin.
> >
> > Anyway, I was surprised to find a doc who had no problem with my current meds, and who is willing to tweek out the details. A soft lifeless genital organ is my concern. He says this soft relaxed muscle condition is common with any alpha or beta agonist. I would welcome any and all feedback from anyone.
> > Thank you,
> > John
poster:michael
thread:48342
URL: http://www.dr-bob.org/babble/20001102/msgs/48487.html