What is it about grapefruit specifically that messes with pretty much every prescription in existence?
In:
It consumes an enzime in our bodies that deals with processing most medicines.
You eat the grapefruit, loose those enzimes. They quickly regrow, usually around the time you’ve had a second or third dose of your meds, while the previous ones are still unprocessed in you. Now your body goes and processes the drugs all at once, causing an OD.
So other citrus doesn’t have this character? I wonder why.
Grapefruit inhibits a liver/ intestinal enzyme called CYP3A4 which is responsible for a large amount of drug metabolism. This can lead to either the drug not getting where it needs to go, or a build-up of the drug which can be dangerous
Pretty sure it either suppresses or induces cytochrome p450 which is involved in a lotttt of medication metabolism. So depending which, it would either decrease or increase blood levels of the medication which would obviously be problematic. Same mechanism by which a lot of medications mess with other ones.
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When you ingest a medication it has to be broken down. Your liver has enzymes to do that, called cytochrome P450 (CYP450). There’s different types CYP450, but the most common one that break down a lot of medications (but not “every prescription in existence” though) is called CYP3A4. Grapefruit, in very large quantities, inhibits CYP3A4 from doing its job. Medications that need CYP3A4 to be metabolized and broken down will now stay in your system, build up and potentially increase the risk of toxicity/adverse effects.
Your body gets rid of medications in two main ways (there are others but these are the main two): pee them out or process them in your liver so the medications are inactivated and then pee or poop the inactivated medications out. There are a collection of enzymes in your liver (enzymes are kind of like fuel that powers the inactivation process) that modify medications so that they are inactivated. These enzymes can be turned up by some substances and can be turned down by others. Grapefruit is one of the substances that turns the enzymes down. So your body can’t clear medications as quickly -> you grt higher levels of medications in your body -> toxicity can occur.
Source: final year med student
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I’m seeing a lot of partially correct answers, so I wanted to point out that there are multiple different mechanisms in which grapefruit can interfere with drug metabolism. All of them are caused by certain chemical compounds found in the citrus (called furanocoumarins). The three main ways they can do this are:
1. Inhibit metabolizing enzymes from breaking down the active form of the drug to the inactive form. This can lead to increased concentration of the drug in your body which can be toxic and lead to overdose (lots of drugs are affected this way, such as antidepressants and cholesterol medications)
2. Inhibit metabolizing enzymes from activating a prodrug to the active form of the drug. This can lead to decreased concentration of the functional drug in your body, reducing the drugs effectiveness. (Certain blood thinners are affected this way)
3. Blocks intestinal transport proteins from absorbing the drug from your digestive tract into your blood stream. This causes the drug to pass through your body without being absorbed, reducing the drug’s effectiveness (Allegra is affected in this way)
For mechanisms 1 and 2, if only small amounts of grapefruit is consumed, only the intestinal metabolic enzymes are affected, meaning that only drugs taken orally would be impacted. If lots of grapefruit is consumed, liver enzymes are also affected, which means that drugs taken via any administration method are impacted.
Pharmacist here. Grapefruit produces some compounds which are metabolized (broken down) by a family of enzymes called CYP3A4 (cytochrome p450 3A4). If my memory serves me right, the compounds are called coumarins which are related in structure to the blood thinner warfarin. Basically if someone has enough grapefruit or it’s juices, the body’s CYP3A4 enzymes will now have to spend time breaking the coumarins down in addition to whatever drug also needs that enzyme to be degraded. Most drugs have both major and minor enzymes involved in their degradation, but the minor enzymes typically will take much longer to break down the drug as they are typically less efficient and break down the drug in less than an optimal fashion. This results in the drug of choice taking much longer to get broken down and removed from the body, resulting in a longer half-life.This means the amount of time the drug will carry out its effects on its target will be increased, sometimes 5-6x or even more (I can’t remember the specific drug, but do remember a drug with a 4-6 hour half life taking more than 5-6 days to leave the body because it’s metabolism was so dependent on the 3A4 complex with the minor enzyme because less than 10% as efficient as 3A4). To be fair it’s not every drug in existence (although I realize OP is speaking hyperbole), but it is a fair number of them – my guess is around 25-30% of drugs will rely on CYP3A4. Some of these will be highly effected while others just marginally slowed.
Edit: TL;DR – imagine leaving a city at 3am… you have no traffic to contend with. This is your 3A4 system without grapefruits compounds competing with whatever drug youve take that’s dependent on the 3A4 system for metabolism. Now imagine leaving the city at 430pm during rush hour traffic. This is akin to the drug of interest competing with the grapefruits compounds for enzymatic degradation.
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