Adverse Drug Reactions

[Pat Robinson]

Let's say that an automobile manufacturer produces a car which randomly accelerates in traffic, or suddenly slows down on the highway --- if you drank grapefruit juice yesterday.

• What if the car suddenly accelerated in city traffic because you had lemonade at lunch?
• Or if eating broccoli caused the car to slow down while entering the highway?

• Would you want to buy that car?

• Drive that car?

Who would be responsible for the severe traffic accidents ('adverse car reactions') and deaths if the manufacturer did not inform you about the dangers of driving their car when drinking grapefruit juice, lemonade, broccoli, cruciferous vegetables, green/black tea, milk, spinach, carrots, parsley, celery, fennel, etc? What if smoking tobacco might cause the car to react abnormally?


When the MD prescribes buying a certain vehicle, would he be accountable to inform you about the foods which might make that specific car have severe "adverse car reactions" and potentially fatal accidents, before you drive the car?

Would the manufacturer be criminal to clinically test the car for "safety" and "efficacy" with robot drivers who don't eat those foods, but then sell the car to the public without informing them about the dangers of the car when eating and drinking normally?

That is what happens when the pharmaceutical manufacturer produces a drug which becomes toxic in the body, if you drank grapefruit juice yesterday.

• And some drugs will suddenly accelerate the chemical availability in your bloodstream because you had lemonade at lunch.
• And 90% of drugs do not provide the intended chemical effect when eating many regular foods. For instance, eating broccoli could cause the drug chemicals to slow down while entering your blood, causing lack of intended effect.

When we swallow pharmaceutical chemicals those chemicals must be detoxified by the body. Eating normal foods improves or slows down the way that the liver (primarily) detoxifies chemicals.

• About 20% of Americans have an impairment in the CY P450 enzyme needed to detoxify drugs.
• The drug manufacturer does clinical trials of their drugs for "safety" and "efficacy" only on people who do not have an impaired CY P450 enzyme.
  
  
  
  • "This table includes a listing of the 6 major cytochrome P450 isozymes involved in drug metabolism and the drugs that are metabolized by them. We recommend using this or another table as a quick reference for detection of potential drug interactions."
  • "If 2 drugs are metabolized by the same cytochrome P450 isozyme, it is very possible that competitive inhibition could lead to higher than usual levels of either or both of the drugs. If a drug is metabolized by a specific cytochrome P450 and is taken with an inhibitor or inducer of that isozyme, an interaction is also likely."
  • Not to mention, liver disease "can be associated with reduced metabolic clearance and higher plasma levels of drugs extensively metabolized by the liver."
  • And, "heart failure reduces liver blood flow and causes a reduction in clearance for drugs."
    
    http://www.fda.gov/drugs/developmentapprovalprocess/developmentreso...

Per FDA recommendations, drug manufacturers don't include people in the clinical trials who they know might be harmed by their drugs becoming toxic due to their impaired CY P450 enzyme. But the FDA approves the drug to be sold to the public without informing them about the dangers of the drug for people with the CY P450 enzyme. The MDs prescribe the drug for drug for people without testing for the CY P450 enzyme.

• And what happens when eating and drinking normally and you swallow the drug?

• What happens when taking the drug if you have an impaired CY P450 enzyme?
  
  
• The chemicals accelerate and dump excess amounts into the blood stream or slow down and do not provide the intended effect.
• The FDA is concerned about these "adverse drug reactions" after the drugs are put on the market.
  
  That is called "Post-Marketing Research".
  
  
• And MDs are not required to report all potential adverse drug reactions to the FDA.

Have you ever experienced an adverse drug reaction? Did your MD report it to the "Adverse Events Reporting System"?

Let's look at specific drugs such as cholesterol-lowering drugs (statins), antidepressants (SSRIs), reflux medications (PPI), many cardiac drugs, antibiotics, pain medications, antihistamines, NSAIDs, anticonvulsants, Coumadin, theophylline, birth control pills, Tylenol --- all can have "adverse drug reactions" due to the CY P450 enzyme.

• And yet the drugs are sold without regard to your CY P450 genetics.
• And yet the drugs are prescribed without regard to your CY P450 genetics.

But, the drug manufacturer, the FDA, the CDC, and the AMA all know that about 20% of Americans have an impairment in the CY P450 enzyme.

In clinical trials they test for the CY P450 enzyme.

And the drug manufacturer, the FDA, the CDC, and the AMA all know that many normal foods impact the chemical toxicity or availability. But, were you told which drugs cause these toxicity effects when eating normal foods?

What if taking a specific medication while driving caused you to drive the car off the highway or into oncoming traffic killing yourself and causing violence to others? Many drugs have a similar effect causing suicide thoughts, self-harm, suicide, violence and aggression toward others.

• During the "Post Marketing Research" and even in clinical trials these "adverse drug reactions" are documented.
• The CY P450 enzyme is necessary to prevent toxicity of 90% of the drugs on the market.
• About 20% of people have an impaired CY P450 enzyme.

According to the CDC:

• Percent of persons using at least one prescription drug in the past month: 47.9% (2005-2008)

• Percent of persons using three or more prescription drugs in the past month: 21.4% (2005-2008)

• Percent of persons using five or more prescription drugs in the past month: 10.5% (2005-2008)

http://www.cdc.gov/nchs/fastats/drugs.htm


Let's talk about drug-drug interactions when you take two or MORE drugs which must be detoxified by the CY P450 enzyme. Toxicity develops faster as the drug dumps chemicals in an accelerated rate. Or intended drug effects do not occur, if normal foods slow down the chemicals going into the bloodstream.

What about taking FIVE or more prescription drugs at one time?

In the US, the average, 2011:

• child age 0-18 takes 4.1 prescriptions per year

• adult age 19-64 takes 11.9 prescriptions per year

• elderly age 65+ take 28.0 prescriptions per year

http://www.statehealthfacts.org/comparetable.jsp?ind=268&cat=5&...


Total pharmaceutical sales in United States, 2011:
$227,551,806,436

http://www.statehealthfacts.org/comparemaptable.jsp?ind=266&cat=5

That is $227 BILLION dollars.


But, what if about 20% of the people taking those drugs might become toxic when taking the drugs? What if many people could have "adverse drug reactions" when taking drugs and eating normal foods? How many people have "adverse drug reactions" because they are taking too many drugs for the body to detoxify safely?

• According to the FDA, "there are more than 2,216,000 serious Adverse Drug Reactions (ADRs) in hospitalized patients, causing over 106,000 deaths annually.
• Thus, Adverse Drug Reactions would be the 4th leading cause of death—ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths.
• These statistics do not include the number of ADRs that occur outside of the hospital settings."

FDA: http://www.fda.gov/drugs/developmentapprovalprocess/developmentreso...


What are some of the most severe drug reactions when drinking grapefruit juice within 24-48 hours?

"For 43 of the 85 drugs now on the list, consumption with grapefruit can be life-threatening, Dr. Bailey said. Grapefruit juice has been found to significantly increase the oral bioavailability of several drugs metabolized by cytochrome P450 enzyme."

This "grapefruit juice effect" may last for 24 to 48 hours after a single 8-oz glass. Therefore, taking medications at a different time as drinking the grapefruit juice will not necessarily avoid the interaction.

http://well.blogs.nytimes.com/2012/12/17/grapefruit-is-a-culprit-in...
http://www.nursingcenter.com/prodev/ce_article.asp?tid=774959

The science: http://jpet.aspetjournals.org/content/313/1/154.full.pdf

• These drugs can become toxic when taken alongside grapefruit juice.
• The chemicals in the drugs effectively cause a drug overdose (up to three-fold) and more severe side-effects.

• Other fruits including Seville oranges, limes, and pomelos can have the same effect, although sweet orange varieties do not produce this interaction. There is, however, a concern that pomegranate juice can inhibit cytochrome P450 enzymes similar to grapefruit juice. Milk thistle, garlic, ginseng, licorice, St. John's Wort and many vegetables affect the Phase 1 or Phase 2 detoxification, including cruciferous vegetables, green/black tea, lemon juice, carrots, parsley, celery, fennel, etc.

Basically, these drugs must be detoxified by this enzyme which is normally inhibited by some foods. But, the drugs have toxicity effects when consumed with these foods. Additionally, a large portion of the population has an impairment of this detoxification enzyme which causes drugs to become toxic, regardless of avoiding these foods.

• "Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs."
  
  http://www.aafp.org/afp/2007/0801/p391.html
  
  
• People who smoke may require higher doses of some of the medications that are substrates of CYP1A2. In contrast, a smoker would require a decrease in theophylline dosage if, for example, smoking were discontinued and the enzyme no longer induced. This topic has been recently reviewed by Zevin and Benowitz.¹
  
  http://www.fda.gov/drugs/developmentapprovalprocess/developmentreso...

Additionally, many drug-drug combinations cause this same toxicity to develop by inhibiting the CY P450 enzyme.

A-C
Alfentanil (oral)
Amiodarone
Apixaban
Atorvastatin
Buspirone
Clopidogrel
Crizotinib
Cyclosporine

D-F
Darifenacin
Dasatinib
Dextromethorphan
Domperidone
Dronedarone
Eplerenone
Erlotinib
Erythromycin
Everolimus
Felodipine
Fentanyl (oral)
Fesoterodine

H-P
Halofantrine
Ketamine (oral)
Latatinib
Lovastatin
Lurasidone
Maraviroc
Nifedipine
Nilotinib
Oxycodone

P-Z
Pazopanib
Pimozide
Primaquine
Quinine
Quetiapine
Quinidine
Rilpivirine
Rivaroxaban
Silodosin
Simvastatin
Sirolimus
Solifenacin
Sunitinib
Tacrolimus
Tamsulosin
Ticagrelor
Triazolam
Vandetanib
Venurafenib

Verapamil
Ziprasidone

http://abcnews.go.com/blogs/health/2012/11/26/grapefruit-medicine-i...


A list of drugs whose effects are decreased by grapefruit can be found here.
http://www.nature.com/clpt/journal/v92/n5/fig_tab/clpt2012159f2.htm...

http://csuvets.colostate.edu/pain/articlespdf/herbs%20and%20foods%2...

http://www.ncbi.nlm.nih.gov/pubmed/15663291
http://www.ncbi.nlm.nih.gov/pubmed/18968322

http://www.nutritionandmetabolism.com/content/5/1/27

• And yes, hospitals no longer offer grapefruit juice...a patient safety measure put in to place many years ago to avoid these food-drug interactions.
• But, what about the 20% of people with CY P450 enzymes which don't detoxify drugs normally and are prescribed the drugs?
• What about when 90% of the drugs are impacted by eating normal foods?
  
  Are those drugs safe to sell? Safe to prescribe? Safe to take?

Do you have an impaired CY P450 enzyme gene? Do you have "chemical sensitivity" to pharmaceuticals?

• Ask your doctor, "Does this medication have a Black Box Warning?". 
• Ask your pharmacist, "Are there any food-drug interactions?".

• Read the drug manufacturer's "package insert" about any reported "adverse drug reactions" BEFORE taking any medication.

NOTE: Reporting of adverse events and medication errors by healthcare professionals and consumers is voluntary in the United States.

• Check RxISK.org website for any reported "adverse drug reactions" before taking medication.
• Create a report to send to your country's drug regulator.

• Report adverse drug reactions to your doctor.
• Report adverse drug reactions to the government's reporting system:
  
  http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm
  
  

"Health care providers have misconceptions about reporting ADRs.^1–3 These misconceptions include the ideas that: 1) All serious ADRs are documented by the time a drug is marketed; 2) It is hard to determine if a drug is responsible for the ADR; 3) ADRs should only be reported if absolute certainty exists that the ADR is related to a particular drug; and, finally, 4) One case reported by an individual physician does not contribute to medical knowledge. Let’s look at each one of these points. 

    1) As we have seen, rare ADRs are usually NOT documented by the time a drug is marketed. 

    2) It can be hard to determine if an individual drug caused a reaction in a complicated patient receiving multiple medications. However, the temporal relationship of a reaction with regard to the administration of a new medication can be helpful. Also, biological plausibility (asking if the drug’s mechanism of action makes this possible or likely) can also be helpful. The bottom line is, even when in doubt about whether a drug caused the reaction, report it.

     3) A suspicion of an adverse drug reaction should be reported. A health care provider does not have to be absolutely certain that a drug caused a reaction. All reports contribute to the heightening of the awareness of FDA safety scientists as they monitor all of the evidence to evaluate the potential for drug-related toxicity. 

    4) One individual report CAN make a difference. Many drug withdrawals began with one clinical report that initiated further investigation. In the example case in this module, a single report ultimately led to the removal of terfenadine from the market. This report potentially saved many lives and led to a better understanding of the mechanism involved in causing torsades de pointes. Almost all drugs are now evaluated prior to being released on the market for their potential to induce cardiac arrhythmias, also as a result of this single case report."

http://www.fda.gov/drugs/developmentapprovalprocess/developmentreso...



Pat Robinson, Wellness Educator
Holistic Researcher & Advocate

[Pat Robinson]

(Reuters) - Toyota Motor Corp has agreed to pay as much as $1.4 billion to settle U.S. litigation claims that its vehicles suddenly and unintentionally accelerated, according to court filings made public Wednesday.

http://in.reuters.com/article/2012/12/26/usa-toyota-settlement-idIN...


Will the pharmaceutical companies receive a similar slap on the hand in court --- someday?