Blood Pressure drugs and fruit.

[interested]

I have recently being having a problem with my blood pressure, my medication appeared not to be working, the doctors increased the dose but still it was high 150/105 resting pulse 90 typically. I had put this down to increased stress via builder from hell. I use perondopril 4mg + indapomide 1.25mgIs there any correlation between eating oranges and drugs not working

I am aware grapefruits stop heart medication working. Last year my wife got into jam making using oranges, figs etc. My neighbour also has orange trees and has also been giving me bags full of oranges to eat. For the last two days I have stopped eating oranges and not eaten any more jams made by my wife. My blood pressure this morning was back down to 130/85 pulse 65. which is normal for me when my medication is working. 

Is there a list of fruits or other foods that can block heart medication from working.

I suspect my wife may have been killing me with kindness literally  

 

[StringJunky]

If you have cause for concern, don't take them  within  2 hours of each other, which is roughly about how long stuff stays in the stomach. Better off asking your doctor if interactions are possible.

[interested]

2 hours ago, StringJunky said:

If you have cause for concern, don't take them  within  2 hours of each other, which is roughly about how long stuff stays in the stomach. Better off asking your doctor if interactions are possible.

I did and payed privately to see a specialist, who did extensive tests. He told me to increase from 2mg to 4mg perondopril. The tests I had only showed two anomolies apart from my BP being high. Raised LDL cholesterol treatable with statins but was told since I was on a diet, I could expect raised LDL cholesterol as a side effect. The other was raised acid levels in the urine, which the specialist was not concerned about.

The raised acid levels may have been due to the amount of oranges, and marmalade compote I was consuming. Compote in yogurt is very nice.

I now have had a trawl of the internet and have confirmed that seville oranges used for marmalade are as bad as grapefruit for blocking the effects of ace inhibitors. Better still my BP is now down to 106/82. I might have to reduce my perondopril back to 2mg if the pressure keeps dropping.

I thought it might be interesting to know how various chemicals in foods can block or increase the effect of drugs. Reliable information is hard to find, and even if you see a specialist they dont always know never mind a GP. 

[CharonY]

You'll have to be careful, the pharmacokinetics are not trivial. For grapefruit and related fruits (e.g. pomelo) the main mechanism is blocking of an enzyme (CYP3A4) that is relevant for the breakdown of drugs (and metabolites). I.e. the fruit blocks its activity and the drug sticks around longer than it should. This effect can take a long time to wear off. A secondary effect, that is also seen in orange juice, shows an opposite effect. They reduce the uptake of drugs from the intestines into the bloodstream. So the net effect (either increasing or decreasing the target dose) depends on the drug and the amount you are taking. So the situation is not quite straightforward.

However, specifically for beta blockers I have only seen three examples published (grapefruit, orange and apple juice) that have shown reduced uptake. The assumption is that naringin-like substances may responsible. In grapefruit juice, naringin was found to block a specific transporter, but to my knowledge in organge and apple juice the precise component is not known. 

 

[interested]

11 minutes ago, CharonY said:

You'll have to be careful, the pharmacokinetics are not trivial. For grapefruit and related fruits (e.g. pomelo) the main mechanism is blocking of an enzyme (CYP3A4) that is relevant for the breakdown of drugs (and metabolites). I.e. the fruit blocks its activity and the drug sticks around longer than it should. This effect can take a long time to wear off. A secondary effect, that is also seen in orange juice, shows an opposite effect. They reduce the uptake of drugs from the intestines into the bloodstream. So the net effect (either increasing or decreasing the target dose) depends on the drug and the amount you are taking. So the situation is not quite straightforward.

However, specifically for beta blockers I have only seen three examples published (grapefruit, orange and apple juice) that have shown reduced uptake. The assumption is that naringin-like substances may responsible. In grapefruit juice, naringin was found to block a specific transporter, but to my knowledge in organge and apple juice the precise component is not known. 

 

Thanks for that Narangin is also found in seville oranges https://www.sciencedirect.com/science/article/pii/S0149291812004882

[Strange]

15 minutes ago, interested said:

Thanks for that Narangin is also found in seville oranges https://www.sciencedirect.com/science/article/pii/S0149291812004882

The wikipedia page says "This would suggest than an inhibitor other than naringin ... may be at work."

https://en.wikipedia.org/wiki/Naringin

Does this mean that marmalade may also be a problem!?

[CharonY]

32 minutes ago, Strange said:

The wikipedia page says "This would suggest than an inhibitor other than naringin ... may be at work."

https://en.wikipedia.org/wiki/Naringin

Does this mean that marmalade may also be a problem!?

It is a talking about a different target. Naringin and related compounds are suspected to inhibit anion transporters that facilitate transfer of drugs to blood (specifically OATP1A2).

The inhibition of the cytochrome (which would have the opposite effect, as that would increase biovailability) is known to be mediated by furancoumarins.

[Strange]

3 minutes ago, CharonY said:

It is a talking about a different target.

Thanks. I missed that.

[interested]

17 hours ago, Strange said:

Does this mean that marmalade may also be a problem!?

Yes, Seville oranges are used for making marmalade. Some other types of oranges do not have naringin and may be ok for me to eat. 

It should be born in mind I was eating a large number of oranges as well as eating marmalade and compote made from oranges. 

Interestingly for me at least. I went out and had an abundant amount of alcohol last night with friends since I have been on the wagon for a while trying to drop my blood pressure, this morning my BP is 130/83 which is still very acceptable, my resting pulse however is 100, and I have a cerebral edema and might not drink again today at least.

Perhaps eating all things in moderation applies to oranges as well as alcohol.

 

 

[John Cuthber]

23 hours ago, StringJunky said:

If you have cause for concern, don't take them  within  2 hours of each other, which is roughly about how long stuff stays in the stomach. Better off asking your doctor if interactions are possible.

At least part of the interaction doesn't take place in the stomach so the 2 hour residence time is irrelevant.

[StringJunky]

1 hour ago, John Cuthber said:

At least part of the interaction doesn't take place in the stomach so the 2 hour residence time is irrelevant.

MyI intention wasn't on about eliminating it completely  but reducing it... it's not irrelevant.

Quote

The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food. In addition, the physiological response to food intake, in particular, gastric acid secretion, may reduce or increase the bioavailability of certain drugs.3^,4  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191675/

 

[interested]

39 minutes ago, StringJunky said:

 

The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food. In addition, the physiological response to food intake, in particular, gastric acid secretion, may reduce or increase the bioavailability of certain drugs.3^,4  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191675/

The conclusion in the link reads

Conclusion

A large number of drugs are introduced every year. Food-drug interactions can produce negative effects in safety and efficacy of drug therapy, as well in the nutritional status of the patient. Generally speaking, drug interactions are to be avoided, due to the possibility of poor or unexpected outcomes. Like food, drugs taken by mouth must be absorbed through the lining of the stomach or the small intestine. Consequently, the presence of food in the digestive tract may reduce absorption of a drug. Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating. Like drugs, foods are not tested as comprehensively so they may interact with prescription or over-the-counter drugs. The authors would suggest patients to tell their doctors and pharmacists about their food intake and dietary supplements so that interactions can be avoided.

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None of my medication has ever said dont take with grapefruits or seville oranges even though it is known they can completely block the action of perondoril. There is not even a basic statement like citrus fruit could stop perondopril from working. I heard of the grapefruit link a long time ago and so avoid it, I had not heard about other fruits causing a problem. I think the law needs to change, how many people must have had heart attacks or strokes because they inadvertently consumed the wrong sort of fruit.

If the penny had not dropped for me ref oranges, I could be well on the way to having a heart attack, brain hemorrhage or stroke right now. 

Edited March 10, 2018 by interested

[StringJunky]

Just prior to your highlight : "Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating".

[interested]

3 hours ago, StringJunky said:

Just prior to your highlight : "Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating".

Having had a scare I think it is safer not to eat the grapefruits or seville oranges when taking perondopril. If my medication ever stops working in the future I know now to check what I am eating. 

You may be correct with the 2 hour wait, what I had been doing was waking up, taking my pills, then having breakfast consisting of 2 or 3 oranges or perhaps plain greek yogurt with orange compote poured over it. Its back to plain yogurt and honey for me or maybe some cereals for breakfast. 

@ anyone Are there any other fruits or food which are likely to block the function of ACE inhibitors like perondopril?

 

Edited March 10, 2018 by interested

[StringJunky]

14 minutes ago, interested said:

Having had a scare I think it is safer not to eat the grapefruits or seville oranges when taking perondopril. If my medication ever stops working in the future I know now to check what I am eating. 

You may be correct with the 2 hour wait, what I had been doing was waking up, taking my pills, then having breakfast consisting of 2 or 3 oranges or perhaps plain greek yogurt with orange compote poured over it. Its back to plain yogurt and honey for me or maybe some cereals for breakfast. 

@ anyone Are there any other fruits or food which are likely to block the function of ACE inhibitors like perondopril?

 

Yes, I agree, I  would play safe and possibly look for alternatives to those fruits.

[CharonY]

On 3/10/2018 at 8:57 AM, StringJunky said:

Just prior to your highlight : "Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating".

Careful about that. CYP3A4 inhibition is known to last for many hours, with reports of up to 24h. I.e. the effect can accumulate.

[interested]

36 minutes ago, CharonY said:

Careful about that. CYP3A4 inhibition is known to last for many hours, with reports of up to 24h. I.e. the effect can accumulate.

Thanks for that observation, Seville oranges are of the menu.

[StringJunky]

31 minutes ago, CharonY said:

Careful about that. CYP3A4 inhibition is known to last for many hours, with reports of up to 24h. I.e. the effect can accumulate.

Noted, but notice it does say "Often", which allows for exceptions. If I was doing something long-term, I would be drilling my GP or the NHS Helplinefor contraindications... I wouldn't be asking here unless I wanted some particular academic detail.

[CharonY]

9 minutes ago, StringJunky said:

Noted, but notice it does say "Often", which allows for exceptions. If I was doing something long-term, I would be drilling my GP or the NHS Helplinefor contraindications... I wouldn't be asking here unless I wanted some particular academic detail.

Sure, but in this context precision is relevant. The precise nature of the interaction with certain drugs are complex and can have opposite effects (i.e. higher or lower bioavailability) based on the drug-juice combination. Certain anti-hypertensive drugs  have been shown to be affected by grapefruit intake (effectively increasing the dosage), requiring about 2-3 days to reset the dosages. Most ACE inhibitors have not shown any known interactions, whereas others are inhibited. In other words, general trends cannot be really translated into specific interactions.

[StringJunky]

26 minutes ago, CharonY said:

Sure, but in this context precision is relevant. The precise nature of the interaction with certain drugs are complex and can have opposite effects (i.e. higher or lower bioavailability) based on the drug-juice combination. Certain anti-hypertensive drugs  have been shown to be affected by grapefruit intake (effectively increasing the dosage), requiring about 2-3 days to reset the dosages. Most ACE inhibitors have not shown any known interactions, whereas others are inhibited. In other words, general trends cannot be really translated into specific interactions.

Right.