needtogetaas
07-09-2010, 10:43 PM
We have all gotten medication from the pharmacy at one time or another. How many of us read the warning? Even more so how many of us read the little pamphlet that on drug interactions they give you with the medication. You know the little folded up peace of paper with thousands of tiny words.
Well Of course I am write lolol.. Every time i read one there is something that sticks out to me. Almost all of them always say " do not consume with grapefruit juice do to harmful interactions" or something along these lines. Some medications it interacts so much that they find it important to put this directly on the bottle.
So of course this got me thinking why? How does Grapefruit juice effect medication?
So I did some research and I found out as always.
A enzymes in the liver called CYP3A4 and CYP1A2 are responsible for the rake down of many things "including medications. They even does the job of braking down mythelation and or other oral steroids as well. A sabstance in grapefruit juice known as "Naringin" HAs been medically proven to brake down both the CYP3A4 and CYP1A2 enzymes in the liver.
CYP3A4
YP3A4 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif Endoplasmic_reticulum
and its expression is induced by glucocorticoids
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif Glucocorticoid
and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs which are used today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. The enzyme also metabolizes some steroids and carcinogens.[3] (http://en.wikipedia.org/wiki/CYP3A4#cite_note-entrez-2)
Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to increase circulating drug levels.
The discovery that grapefruit juice can increase the oral availability of some medications was an accidental discovery made when grapefruit juice was used to mask the taste of ethanol in a study involving the calcium channel blocker felodipine. Since then, more different drugs have shown to enhance oral availability when consumed with grapefruit juice. Most of the drugs affected by grapefruit juice have highly variable oral bioavailability. In addition, most of these drugs are chiefly metabolized in the body by CYP3A4, an enzyme present in the liver and intestine.
The major effect of grapefruit juice appears to reduce “first-pass” metabolism by reducing CYP3A4 activity.
As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine but to some degree within the liver
After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression. Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours. The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.
Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice/–naringin drug interactions. An effect is seen with the whole fruit as well as its juice,and naringin extracts so caution should be exercised with ALL. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect. A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.
There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability. The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.
What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports, it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.
One of the things I found most interesting is when you look for a list of drugs effected by grapefruit juice every known list has "dbol" on this list of drugs effected by grapefruit juice. This means that dbol is Highly effected by the CYP3A4 pathway! and i suspect that many other oral drugs also do go by route of CYP3A4 pathway.
Also a drug known as Cyprotraine a anti androgen/dht, is metabolized by the CYP3A4
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif CYP3A4
enzyme, forming the active metabolite 15β-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity. Cyproterone acetate increases production of CYP3A4.
Dutasteride and SERMs are also metabolized by the CYP3A4 enzyme.
And lastly here is another list of drugs effected my the p450 enzyme system .
Statins (Cholesterol Lowering Drugs):
-Baycol (Cerivastatin)
-Mevacor (Lovastatin)
-Lipitor (http://rxhealthdrugs.com/brand.php?cat=3&id=168&promo=true) (Atorvastatin (http://rxhealthdrugs.com/brand.php?cat=3&id=168&promo=true))
-Zocor (http://rxhealthdrugs.com/brand.php?cat=3&id=170&promo=true) (Simvastatin (http://rxhealthdrugs.com/brand.php?cat=3&id=170&promo=true))
Antihistamines:
-Ebastine
-Seldane (Terfenadine, taken off the U.S. market)
Calcium Channel Blockers (Blood Pressure Drugs):
-Nimotop (Nimodipine)
-Nitrendipine
-Plendil (Felodipine)
-Pranidipine
-Sular (Nisoldipine)
Psychiatric Medications:
-Buspar (Buspirone)
-Halcion (Triazolam)
-Tegretol (Carbamazepine)
-Valium (Diazepam)
-Versed (Midazolam)
Intestinal Medications:
-Propulsid (Cisapride, taken off the U.S. market)
Immune Suppressants:
-Neoral (Cyclosporine)
-Prograf (Tacrolimus)
Pain Medications:
-Methadone
Impotence Drug:
-Viagra (http://www.eclenbuterol.com/viagra-p195.html) (Sildenafil (http://rxhealthdrugs.com/brand.php?cat=275&id=20&promo=true))
Miscellaneous
-Losartan (http://www.4rx.com/promos/elitefitness/products/generic-dostinex.html) (Angiotensin II receptor blocker - ARB) - Grapefruit juice inhibits the body's ability to absorb the drug.
-Digoxin (for treating congestive heart failure) - Grapefruit juice inhibits the body's ability to absorb the drug.
Simple put many oral steroids are greatly enhanced by grapefruit juice or the extract naringin.
__________________
Well Of course I am write lolol.. Every time i read one there is something that sticks out to me. Almost all of them always say " do not consume with grapefruit juice do to harmful interactions" or something along these lines. Some medications it interacts so much that they find it important to put this directly on the bottle.
So of course this got me thinking why? How does Grapefruit juice effect medication?
So I did some research and I found out as always.
A enzymes in the liver called CYP3A4 and CYP1A2 are responsible for the rake down of many things "including medications. They even does the job of braking down mythelation and or other oral steroids as well. A sabstance in grapefruit juice known as "Naringin" HAs been medically proven to brake down both the CYP3A4 and CYP1A2 enzymes in the liver.
CYP3A4
YP3A4 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif Endoplasmic_reticulum
and its expression is induced by glucocorticoids
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif Glucocorticoid
and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs which are used today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. The enzyme also metabolizes some steroids and carcinogens.[3] (http://en.wikipedia.org/wiki/CYP3A4#cite_note-entrez-2)
Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to increase circulating drug levels.
The discovery that grapefruit juice can increase the oral availability of some medications was an accidental discovery made when grapefruit juice was used to mask the taste of ethanol in a study involving the calcium channel blocker felodipine. Since then, more different drugs have shown to enhance oral availability when consumed with grapefruit juice. Most of the drugs affected by grapefruit juice have highly variable oral bioavailability. In addition, most of these drugs are chiefly metabolized in the body by CYP3A4, an enzyme present in the liver and intestine.
The major effect of grapefruit juice appears to reduce “first-pass” metabolism by reducing CYP3A4 activity.
As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine but to some degree within the liver
After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression. Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours. The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.
Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice/–naringin drug interactions. An effect is seen with the whole fruit as well as its juice,and naringin extracts so caution should be exercised with ALL. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect. A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.
There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability. The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.
What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports, it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.
One of the things I found most interesting is when you look for a list of drugs effected by grapefruit juice every known list has "dbol" on this list of drugs effected by grapefruit juice. This means that dbol is Highly effected by the CYP3A4 pathway! and i suspect that many other oral drugs also do go by route of CYP3A4 pathway.
Also a drug known as Cyprotraine a anti androgen/dht, is metabolized by the CYP3A4
http://needtobuildmuscle.net/forum/images/misc/wikipedia_icon.gif CYP3A4
enzyme, forming the active metabolite 15β-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity. Cyproterone acetate increases production of CYP3A4.
Dutasteride and SERMs are also metabolized by the CYP3A4 enzyme.
And lastly here is another list of drugs effected my the p450 enzyme system .
Statins (Cholesterol Lowering Drugs):
-Baycol (Cerivastatin)
-Mevacor (Lovastatin)
-Lipitor (http://rxhealthdrugs.com/brand.php?cat=3&id=168&promo=true) (Atorvastatin (http://rxhealthdrugs.com/brand.php?cat=3&id=168&promo=true))
-Zocor (http://rxhealthdrugs.com/brand.php?cat=3&id=170&promo=true) (Simvastatin (http://rxhealthdrugs.com/brand.php?cat=3&id=170&promo=true))
Antihistamines:
-Ebastine
-Seldane (Terfenadine, taken off the U.S. market)
Calcium Channel Blockers (Blood Pressure Drugs):
-Nimotop (Nimodipine)
-Nitrendipine
-Plendil (Felodipine)
-Pranidipine
-Sular (Nisoldipine)
Psychiatric Medications:
-Buspar (Buspirone)
-Halcion (Triazolam)
-Tegretol (Carbamazepine)
-Valium (Diazepam)
-Versed (Midazolam)
Intestinal Medications:
-Propulsid (Cisapride, taken off the U.S. market)
Immune Suppressants:
-Neoral (Cyclosporine)
-Prograf (Tacrolimus)
Pain Medications:
-Methadone
Impotence Drug:
-Viagra (http://www.eclenbuterol.com/viagra-p195.html) (Sildenafil (http://rxhealthdrugs.com/brand.php?cat=275&id=20&promo=true))
Miscellaneous
-Losartan (http://www.4rx.com/promos/elitefitness/products/generic-dostinex.html) (Angiotensin II receptor blocker - ARB) - Grapefruit juice inhibits the body's ability to absorb the drug.
-Digoxin (for treating congestive heart failure) - Grapefruit juice inhibits the body's ability to absorb the drug.
Simple put many oral steroids are greatly enhanced by grapefruit juice or the extract naringin.
__________________