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Levitra and grapefruit

Some fruit juices and fruits can levitra and grapefruit interact with numerous drugs, in many cases causing adverse effects. 1, the levitra and grapefruit effect was first discovered by accident, when a test of drug interactions with alcohol used grapefruit levitra and grapefruit juice to hide the taste of the ethanol. 2, it is still best-studied with grapefruit and grapefruit juice, 1 but similar effects have more recently been seen with some (not all) other citrus fruits., one medical review advises patients to avoid all citrus juices until further research clarifies the risks. 7, the interacting chemicals are found in many plants, citation needed and so many other foods may be affected; effects have been observed with apple juice, but their clinical levitra and grapefruit significance is not yet known. 8 9 4, normal amounts of food and drink, such as one whole grapefruit or a small glass (200 mL (6.8 US fl oz) of grapefruit juice, can cause drug overdose toxicity. 1, fruit consumed three days before the medicine can still have an effect. The relative risks of different types of citrus fruit have not been systematically studied. 1, affected drugs typically have an auxiliary label saying Do not take with grapefruit on the container, and the interaction is elaborated on in the package insert. 11, people are also advised to ask their physician or pharmacist about drug interactions. 11, the effects are caused by furanocoumarins (and, to a lesser extent, flavonoids ). These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4). CYP3A4 is a metabolizing enzyme for almost 50 of drugs, and is found in the liver and small intestinal epithelial cells. 12 As a result, many drugs are affected. Inhibition of enzymes can have two different effects, depending on whether the drug is either metabolized by the enzyme to an inactive metabolite, or activated by the enzyme to an active metabolite. If the active drug is metabolized by the inhibited enzyme, then the fruit will stop the drug being metabolized, leaving elevated concentrations of the medication in the body, which can cause adverse effects. 11 Conversely, if the medication is a prodrug, it needs to be metabolised to be converted to the active drug. Compromising its metabolism lowers concentrations of the active drug, reducing its therapeutic effect, and risking therapeutic failure. Low drug concentrations can also be caused when the fruit suppresses drug absorption from the intestine. 13 Contents History edit The effect of grapefruit juice with regard to drug absorption was originally discovered in 1989. The first published report on grapefruit drug interactions was in 1991 in the Lancet entitled "Interactions of Citrus Juices with Felodipine and Nifedipine and was the first reported food-drug interaction clinically. However, the effect only became well-publicized after being responsible for a number of bad interactions with medication. Active ingredients edit Citrus fruits may contain a number of polyphenol compounds, 4 15 including the flavonoid naringin and furanocoumarins (such as bergamottin, dihydroxybergamottin, bergapten, and bergaptol ) citation needed. These are natural chemicals. They may be present in all forms of the fruit, including freshly squeezed juice, frozen concentrate, and whole fruit. Citation needed Grapefruit, Seville oranges, 15 bergamot, 16 and possibly other citrus also contain large amounts of naringin. It can take up to 72 hours before the effects of the naringin on the CYP3A4 enzyme are seen. This is problematic as a 4 oz portion of grapefruit contains enough naringin to inhibit the metabolism of substrates of CYP3A4. Naringin is a flavonoid which contributes to the bitter flavour of grapefruit. 6 Furanocoumarins seem to have a stronger effect than naringin under some circumstances. 17 15 Mechanism edit Organic compounds that are derivatives of furanocoumarin interfere with liver and intestinal enzyme CYP3A4 and are believed to be primarily responsible for the effects of grapefruit on the enzyme. 18 Cytochrome isoforms affected by grapefruit components also include CYP1A2, CYP2C9, and CYP2D6. 19 Bioactive compounds in grapefruit juice may also interfere with MDR1 (multidrug resistance protein 1) and oatp (organic anion transporting polypeptides either increasing or decreasing the bioavailability of a number of drugs. Drugs that are metabolized by these enzymes may have interactions with citrus chemicals.

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