Grapefruit juice caused an OD death!

[BeachBum4u]

I saw a show on the tele the other day and couldn't believe what I was hearing. Turns out a woman died of what appeared to be an overdose. They ran the tox screens and did an autopsy to get the whole picture. The experts concluded that she had drank a good amount of grapefruit juice in addition to a narcotic she was prescribed by her doctor. I'm sorry but I don't recall (or they didn't say) what the drug was or how much exactly she drank. In their report it read that the grapefruit juice had increased the level of the narcotic 3x what it should have been, thus the OD.

I've read on BL where folks use grapefruit juice to boost their narcotic's effects and all I have to say is that if this report is indeed true, please be very careful adding grapefruit juice to your narcotic drug of choice. I had no idea that that stuff could have such a drastic effect! Anyway, just thought I'd post what I'd seen as a fair warning. Please be safe out their everyone.

 

[Swimmingdancer]

Yes it's true that people have overdosed from unknowingly potentiating drugs by drinking huge amounts of grapefruit juice. When I was prescribed opioids they actually had a warning sticker on each pill bottle saying "DO NOT CONSUME GRAPEFRUIT".

However, if you are using grapefruit juice in an educated manner to deliberately potentiate something, knowing full well that it will have that effect and therefore taking less opioids (it's mostly opioids that people try to potentiate this way on BL) than usual it is much safer. It's still prudent to be very aware that you can't know exactly how much whatever amount of grapefruit juice you are drinking will potentiate your opioids and not to just drink it on top of a dose that would normally be near the top end of your tolerance level. There are around 80-90 drugs that grapefruit can interact with, not just opioids, so if you're someone that drinks vast quantities of grapefruit juice or eats tons of grapefruits it's important to check for interactions with any drugs you are taking.

One woman who lived off only grapefruit for a week was hospitalized because of it potentiating the drug she was taking, verapamil. In my experience with the drugs I have taken drinking a glass of grapefruit juice or eating a grapefruit had no perceptible effect, to be honest.

 

[electrodevo]

The "drastic effect" is probably why some people take grapefruit juice for all I know... *shrug*

Bergamottin is the relevant chemical, it inhibits certain liver enzymes that break chemicals down -- CYP3A4 in particular.

It could be a problem with prescribed narcotics, I imagine, if people follow a "take X pills daily" type regime. That regime assumes that the drug has cleared the system before a new dose is added. If grapefruit juice inhibition means that the drug is still floating in the system, it could lead to an OD problems. Some deaths from certain antihistamines in particular are noted in the Wiki.

The only compounds grapefruit juice affects (listed in the Wiki), that are commonly talked about here, are DXM, opioids, and benzodiazepines.

 

[BeachBum4u]

I "am" prescribed narcotics daily but fortunately for me, although I love grape juice, I loath grapefruit juice. Even the smell of it can make me sick. I have no idea how someone can eat or drink grapefruits.

 

[Jabberwocky]

mmm i love grapefruits. i like the juice too (not even for the potentiation effects).

this doesn't surprise me tbh. it clogs up the enzymes thereby allowing more of a lets call it prodrug opiate to convert into a higher amount of its more potent form. lets take oxycodone for instance. if you take oxycodone on its own you will produce 10% oxymorphone which apparently through tests: "concluded that oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain". now, clog your enzymes hard enough and that 10% number drastically increases. It can shoot to around 30-40%. if you're a hardcore oxy user taking 400mg daily, perhaps you'd survive that amount of oxymorphone just due to your opiate tolerance all together. however, if you're not really used to opiates and the lot - those numbers are terrifying.

if you were taking a straight forward drug such as hydromorphone or morphine there is no "pro-drug" that these can produce. however, due to the enzymes clogging you will effectively hold these drugs in your system for a longer period of time. it's essentially turning a morphine 4 hour half life into an 8 hour half life, maybe longer. everytime you top up, you're getting more and more and more until eventually kaput.

 

[Swimmingdancer]

mmm i love grapefruits. i like the juice too (not even for the potentiation effects).

this doesn't surprise me tbh. it clogs up the enzymes thereby allowing more of a lets call it prodrug opiate to convert into a higher amount of its more potent form. lets take oxycodone for instance. if you take oxycodone on its own you will produce 10% oxymorphone which apparently through tests: "concluded that oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain". now, clog your enzymes hard enough and that 10% number drastically increases. It can shoot to around 30-40%. if you're a hardcore oxy user taking 400mg daily, perhaps you'd survive that amount of oxymorphone just due to your opiate tolerance all together. however, if you're not really used to opiates and the lot - those numbers are terrifying.

if you were taking a straight forward drug such as hydromorphone or morphine there is no "pro-drug" that these can produce. however, due to the enzymes clogging you will effectively hold these drugs in your system for a longer period of time. it's essentially turning a morphine 4 hour half life into an 8 hour half life, maybe longer. everytime you top up, you're getting more and more and more until eventually kaput.

Not quite correct. I am eating a delicious grapefruit right now btw

So, the interaction grapefruit has on certain drugs is due to 2 factors:
- it inhibits a specific enzyme called CYP3A4 which is involved in the metabolism of many drugs (this is the "clogging" of enzymes you were reffering to - inhibition means that some of the molecules in grapefruit bind to the enzymes, thus decreasing their activity)
- it inhibits p-glycoprotein, which is responsible for transporting drugs to/from various places in the body, including out of the brain

What effect, if any, grapefruit will have on a particular drug greatly varies depending on the specific drug.

With oxycodone, inhibition of CYP3A4 increases some of the effects of oxycodone. The enzyme CYP3A4 converts many opioids, including oxycodone [source], into inactive metabolites. Oxycodone is actually converted to oxymorphone by a different enzyme. So how CYP3A4 inhibition affects oxycodone in order to increase its effects [source] is by slowing it from being deactivated which increases the blood levels as well as making it last longer. This is the same way in which it would affect morphine [source]. The formation of oxymorphone is increased with grapefruit+oxycodone only because there is more oxycodone in the blood [source].

It is suggested that there is probably an effect of some sort due to p-glycoprotein with most drugs too, but it's less understood.

 

[BeachBum4u]

Ssssshhhhheeeeewwwwww - Did you hear that? If not, it was the previous two posts going over my head at a very rapid pace.

Thanks for the info. However I didn't understand any of it but God bless you for knowing those details.

 

[NeighborhoodThreat]

BeachBum, do you have a press release or other way to verify this? I've never heard of this happening (that's not to say it hasn't happened before) but since grapefruit juice is often mentioned as a potentiator throughout Bluelight and the Internet in general. In the interest of HR I feel having a source for this could be useful.

 

[Jktm]

Not quite correct. I am eating a delicious grapefruit right now btw

So, the interaction grapefruit has on certain drugs is due to 2 factors:
- it inhibits a specific enzyme called CYP3A4 which is involved in the metabolism of many drugs (this is the "clogging" of enzymes you were reffering to - inhibition means that some of the molecules in grapefruit bind to the enzymes, thus decreasing their activity)
- it inhibits p-glycoprotein, which is responsible for transporting drugs to/from various places in the body, including out of the brain

What effect, if any, grapefruit will have on a particular drug greatly varies depending on the specific drug.

With oxycodone, inhibition of CYP3A4 increases some of the effects of oxycodone. The enzyme CYP3A4 converts many opioids, including oxycodone [source], into inactive metabolites. Oxycodone is actually converted to oxymorphone by a different enzyme. So how CYP3A4 inhibition affects oxycodone in order to increase its effects [source] is by slowing it from being deactivated which increases the blood levels as well as making it last longer. This is the same way in which it would affect morphine [source]. The formation of oxymorphone is increased with grapefruit+oxycodone only because there is more oxycodone in the blood [source].

It is suggested that there is probably an effect of some sort due to p-glycoprotein with most drugs too, but it's less understood.

More oxymorphone is also produced because of the clogged CYP3A4 enzyme, as well. With 3A4 being taken up by the ingredient in the grapefruit, it kind of forces the oxycodone to go through other enzymes for metabolism. At least that's how I understand it from the way sekio explained the CYP450 series at one point.

edit: And NT, I don't have a source, but I've heard of it happening with older individuals that have eaten grapefruit/drank the juice every breakfast of their lives and get prescribed a strong opioid for whatever aches/pains they have. Since they always have the grapefruit effect going and they're starting out as opioid naive in many cases, the drugs continuously build as they dose according to their doctor's orders and eventually all into respiratory arrest.

 

[Swimmingdancer]

More oxymorphone is also produced because of the clogged CYP3A4 enzyme, as well. With 3A4 being taken up by the ingredient in the grapefruit, it kind of forces the oxycodone to go through other enzymes for metabolism. At least that's how I understand it from the way sekio explained the CYP450 series at one point.

Makes sense. I trust sekio's expertise . That's kind of what I meant to say, that since less than usual is getting deactivated through CYP3A4 there is more oxycodone in the blood and more going through CYP2D6. Not sure if it actually changes the ratio of oxycodone to oxymorphone or not though?

As for drugs like morphine I think it increases the blood levels acutely and not solely through multiple doses.

---

As for people actually dying from grapefruit/drug interactions, the only ones I have heard of were:

- A possible death due to combining Lipitor (cholesterol lowering drug) + grapefruit juice. (There's a case report or something(?), but I can't read it without membership: The grapefruit challenge: the juice inhibits a crucial enzyme, with possibly fatal consequences).

- A death attributed to terfenadine (an especially toxic antihistamine no longer on the market in the US, Canada or UK) toxicity after consuming it with grapefruit juice [Source]

 

[Midazle]

Back when I was Benzo naive I had started Lorazepam for sleep. I had a basic idea of the grapefruit potentiation, anyways I took 1mg of Lorazepam at around 8PM planning to go to bed in two hours or so, well I ended up taking it with Grapefruit juice! I get a text and go to some coffee house event with some band playing and chill with some friends, milady relaxed like Ativan usually is. I get home at around 11:30PM and hop in bed (I had walked home it was a block away) felt unusually amnesic as in forgetful specifically with things I was just thinking about, I knew Ativan has a higher Amnesic effect that Xanax and Klonopin so nothing crazy I thought, soon I feel as though I had taken 30mg of Ambien! I got on Facebook and started talking to this cute blonde girl I had a crush on and managed to get lucky with my words ;P (thats another story though). Woke up the next morning at like 8:30PM late for school, I felt SLAMMED still! I felt like I was straight jammed on heavy doses of Benzo's! I was in my first class and my friends thought I was stoned as hell...eventually it wore off after 10:30 but I honestly can not recall the entire morning before 11:00! It was scary and its not like I took a ton of Ativan or Grapefruit juice, at leasts Im pretty sure as this was when I kept my controlled substances in another room. I would be VERY careful with Grapefruit juice! I used to drink it allot but don't anymore because of the narcotics and what not I have to take.

I also tried Oxycodone and that Quinine or whatever you find in sezler water....had to chuck a bottle and half to get effects but 5mg of Oxycodone felt like 15 and it lasted for 8 hours solid...this was when I was switched from Hydrocodone to Oxycodone and I was so used Hydrocodone's nodding euphoria and just mixing it with the numerous options to potentiate it where as Oxycodone is a bit more speedier and potentiation is different. Ill be looking to start drinking Selzer water with my Oxy possibly for breakthrough pain now though, not sure if its gonna be a great idea but ill see.


EDIT: BTW Thanks to the two great gents up top who gave that wonderful explanation! Even in my current less than conscious state I understood it!

 

[BeachBum4u]

Sorry but I saw it on TV and I don't remember what I was watching. It must be on-line somewhere. Let me do some checking and I'll get back to you.