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c1are
13 Posts |
 Posted - 18 July 2010 : 20:45:52
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Hi, have my short answer paper on tuesday and getting my knickers in a twist about grapefruit juice! Can anyone enlighten me? It is an INHIBITOR of CYP4503A in small intestine AND liver?? Can it ENHANCE action of other drugs at all?
and can anyone explain in idiot's language what on arth an efflux pump inhibitor is? Wikipedia is far too technical!!
Many thanks! |
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debzz1970
2 Posts |
Posted - 19 July 2010 : 08:33:18
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Flipping Heck is this what I am letting myself in for! mentally just ran a mile screaming in the opposite direction. Sorry Clare, I know its no help but when I have moments like this, I google until I get the answer I need.
Keep Smiling! :-) |
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meatbag
9 Posts |
Posted - 19 July 2010 : 09:16:38
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Taken from: http://www.pharmacists.ca/content/hcp/resource_centre/drug_therapeutic_info/pdf/DrugAdministrationGrapefruitJuice.pdf
Drug Administration and Grapefruit Juice
D.G. Bailey, PhD
The following is an overview of drug administration and grapefruit juice consumption. This information is not intended to present a
comprehensive review; the reader is therefore encouraged to seek additional and confirmatory information.
Recently, drug interactions with grapefruit juice have received considerable
attention. The selection of drugs presented in the following table is
based on information contained in product monographs in the CPS and
on information cited in reputable references. The table outlines pharmacokinetic
and pharmacodynamic effects of concurrent grapefruit juice and
drug administration known to date as well as management options. It
should not be assumed that the drugs in the table should never be taken
concomitantly with grapefruit juice or that drugs not appearing in the table
do not interact.
Studies have shown that grapefruit juice acts as an inhibitor of intestinal
isoenzymes. In particular, grapefruit juice inhibits intestinal CYP 3A4-
mediated metabolism which is believed to be responsible for grapefruit
juice effects. There appears to be a prolonged inhibitory effect of grapefruit
juice on intestinal CYP 3A4-mediated metabolism, therefore, separating
the dose of the drug from ingestion of grapefruit juice may not
prevent an interaction. Enzyme inhibition by grapefruit juice has been
shown to increase the serum concentration of drugs with high first-pass
metabolism. Although most studies have used grapefruit juice prepared
from frozen concentrate, all forms of grapefruit (fresh juice and whole fruit
included) have the potential to affect intestinal CYP 3A4.
The exact grapefruit juice constituent responsible for this enzyme
inhibition has not yet been conclusively identified. While sweet orange
juice does not appear to cause the same interaction, sour (Seville) orange
juice has similar enzyme inhibitory effects. The quantity of grapefruit juice
consumed is important to consider, since as little as 250 mL can cause
significant inhibition of CYP 3A4.
The clinical significance of the interaction is determined by the grapefruit
juice-induced change in drug bioavailability relative to the therapeutic
range for the individual drug (i.e., drugs with a wide therapeutic index may
be less affected than drugs with a narrow therapeutic index) and the individual’s
susceptibility (e.g., patients with hepatic insufficiency or pre-existing
medical conditions). Most of the reported studies of interactions with
grapefruit juice are from single-dose studies in healthy volunteers.
Repeated dosing of grapefruit juice may increase the effect of many drugs.
Little or no effect is observed when usual amounts of grapefruit juice
are ingested concomitantly with parenterally administered drugs (e.g., i.v.
midazolam, nifedipine). Also, no interaction would be expected with the
use of transdermal dosage forms (e.g., estradiol-17 patch) since usual
amounts of grapefruit juice have little effect on hepatic CYP 3A4. Large
amounts of grapefruit juice administered under experimental conditions
(e.g., 200 mL double-strength juice three times daily) have been shown to
inhibit hepatic CYP 3A4.
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angela.nagle
73 Posts |
Posted - 19 July 2010 : 09:20:04
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from wikki:
Consumption of grapefruit or grapefruit juice inhibits the metabolism of statins. Furanocoumarins in grapefruit juice (i.e. bergamottin and dihydroxybergamottin) inhibit the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism of most statins (however it is a major inhibitor of only lovastatin, simvastatin and to a lesser degree atorvastatin) and some other medications[45] (it had been thought that flavonoids (i.e. naringin) were responsible). This increases the levels of the statin, increasing the risk of dose-related adverse effects (including myopathy/rhabdomyolysis). Consequently, consumption of grapefruit juice is not recommended in patients undergoing therapy with most statins. An alternative, somewhat risky, approach is that some users take grapefruit juice to enhance the effect of lower (hence cheaper) doses of statins. This is not recommended as a result of the increased risk and potential for statin toxicity.
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c1are
13 Posts |
Posted - 19 July 2010 : 12:15:32
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| Thanks so much guys, that is so kind and helpful of you. I really appreciate it. I had been reading about GJ affecting efflux pumps and affecting reuptake of substrates of certain drugs, but it is relatively minor effect compared to inhibition of CYP450 in intestine, but is why GJ is so unpredictable. But no clinicians in real life seem too concerned about it. I am hoping we won't need so much detail in the exam! |
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meatbag
9 Posts |
Posted - 19 July 2010 : 12:50:10
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No, you're right, many clinicians do not seem overly concerned about the CYP450 inhibition properties of grapefruit juice, in much the same way that many psychiartists are largely unconcerned about the P450 induction properties of tobacco (most notably CYP1A2) which will precipitate lower plasma concentration levels of drugs like Olanzapine - which is very commonly prescribed where I work, and many psychiatric patients are prolific smokers.
But, going back to grapefruit juice; I generally ask patients not to use any fruit juices for the purpose of taking their medication and simply stick to plain old water (as I'm sure that grapefruit juice is not the only fruit juice which can have an effect of P450 induction / inhibition, or so I've read somewhere). |
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Grapefruit juice
