Ativan/Xanax/Cimetidine/Zantac/Diazepam/Grapefruit Juice

For anyone who is interested, I thought you might want to understand how the following drugs can slow you Phase I liver detoxification process down.

The most popular drug treatments for postpartum depression, including fluoxetine (Prozac) and other drugs in its class, slow down phase I detoxification. So do the benzodiazepine tranquilizers, such as alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan); many antibiotics; antihistamines given for allergies; and stomach-acid blockers such as cimetidine (Tagamet) and ranitidine (Zantac). When drugs inhibit phase I detoxification, other toxins (including other drugs) can build up to harmful levels because of the liver’s decreased ability to get rid of them.

Phase I can also be inhibited by nutritious foods. Grapefruit juice contains a substance that inhibits phase I enzymes so strongly that it can cause drug overdoses. The enzymes are slowed so much that they cannot detoxify drugs fast enough, and the levels of the drug in the bloodstream climb too high. Capsaicin, the compound that makes hot peppers hot, also slows down phase I.

My note: Antiarrhythmics probably have similar effects, but couple this with any of the above, and the process is even further degraded.
[www.pregnancyrecovery.com]

I've read that naringenin in grapefruit can lead to beta blocker overdose.

Should someone using a beta blocker also avoid cayenne and black pepper, and salsa? I've use these without apparent trouble.

To have such an effect "overdose" someone must drink grape fruit juice on a regular basis . Grape fruit juice has a short time effect (as an inhibitor) on different cytochrome P450 such as : CYP 1A2 , CYP 2A6 and CYP 3A4 . The lasting effect is about 3H00 .

As a sample of phase 1 detoxication , Beta blockers are metabolised by CYP 2A6 , grape - fruit does'nt seems to inhibit this cytochrome . CYP 2A6 can not be induced . The effectiveness of CYP2A6 depend 100% on genetic polymorphism.

Amiodarone , calcium channel blocker ,digoxine , propafenon, warfine.... are metabolised by CYP 3A4 wich is inhinited by grape fruit . CYP 3A4 can be induced by different substance such as steroid hormone amongst other.

That list is far from being complete of course .

Voila .

Pierre

Pierre, tell me again how long the inhibitory effects of grapefruit consumption last? I didn't understand your units of measurement. 3 what was that?
Peggy

The effect of grape fruit juice is lasting about 3 hour on average . I don't know about extract of grape fruit seed .

Pierre

thanks, Pierre. I don't use grapefruit seed extract at all, but i do eat a grapefruit every 2-3 days so as to stretch the effect of my lisinopril blood pressure medication. I haven't kept good records, but it seems to me that the effect of one grapefruit is still felt the next day and still has a little effect the next day after that. So far this has been allowing me to use 5mg instead of 10mg, and still keep my blood pressure around 120/70. That is very different from 3 hours. Can anybody shed more light on this?
Peggy

Peggy ,

It is not easy to find complete imformation on Cytochrome P450 . If you use google and type " lisinopril cp450" you'll have one article about the mimute of a pharmacist meeting in september 2003 where they say that it looks like lisinopril is not metabolised by Cytochome p450 . I have looked also on www.medscape.com/druginfo . They don't say nothing about interaction between grape fruit and lisonopril . Usually when such a interaction exist , they always say it . I don't have more information about lisinopril and grape fruit. About the 3 Hour , i learn that from a doctor who has a very good experience on that matter . But don't forget detoxification (that's the way i understand it) is always influence by polymorphism even if some part of the process may be influence by other factor. If you have oposite imformation , i'm interested .

Pierre

Pierre, i have only what is called anecdotal information on this, that is, my own experience only. Someplace i came across the information that lisinopril is one of the drugs affected by grapefruit consumption. I have a blood pressure machine that i use to keep track of my blood pressure, and i like grapefruit, and i am on a fixed income and always short of money. So i decided to see if i could cut down on my lisinopril consumption by eating grapefruit. Sure enough, if i peel and eat a nice red grapefruit, for the next 2 days the usual 10mg dose of lisinopril is too strong and depresses my blood pressure to around 100/65. That is too low and tends to make me dizzy.

If i eat a grapefruit this afternoon, and take only 5mg lisinopril tonite instead of 10mg, when i take my bp tomorrow morning it will be around 115-120 over 65-70. Day after tomorrow, with no more grapefruit, the same 5mg dose will produce a reading between 120 and 125 over about 70. By the third day the effect has worn off and 5mg gives a reading about 130-135 over 80-85. One grapefruit every other day or even every third day seems to be about right. Grapefruit is cheaper than lisinopril when taken this way, and one prescription lasts me 2 months instead of one month.

I have never told this to a doctor for fear they would reduce the prescribed dose and wipe out my little money saving scheme. If there is any harm in this practice i would like to know about it. I have been doing it for several years and have not had any trouble so far. I don't believe i would do it with any drug more serious than lisinopril. Thank goodness my health problems are comparatively few.

Any comments on this practice will be welcome. I don't have health insurance so i am pretty much on my own. I have access to a health clinic at a reduced price but it still is a price and i avoid expense where i can.

Peggy

Peggy ,

I don't see no harm in such a practice . However keep in mind that grape fruit does inhibit some Cytochrome P450 and especially CYP 3A4 wich metabolise many different medecine . So , if you do have to take other medication , do check for any interaction with grape fruit .You have to know also that CYP 1A2 wich metabolise Promutagens and procarcinogens substance as well as cafféine is inhibited also by grape fruit . So i have a second thought and i wonder if it is wise to use grape fruit on a daily basis without considering which kind of phase one detoxication you do need the most . As an exemple , The way i undersatnd it , is that if you do smoke , you definitely need CYP 1A2 for detoxication more than a non smoker .

I hope it clarify a bit more , also you can have a look on the recent post of richard about detoxication process , he did a real great job explaining it .

Look at the post "Aldehydes,Tyramines,and our liver ".

Pierre

Thank you Pierre for your good advice. Since the weather has been so bad here i have been stuck in my apartment and have used the time to study the cytochrome P450 system. It is fascinating. The internet is the greatest thing i know about, it has helped me to be better informed about many health related subjects.

You are right that if i were taking any other medication i would have to rethink this practice. I don't smoke and seldom drink so i think i am safe for now.

Pierre, do you have some kind of medical education? You sound as though you might be employed in the medical profession. I am very grateful to you for your advice in this matter, and i always read your posts with great interest.