Tag: drug interactions

Categories : Diet and NutritionTags :

Cinnamon Could Affect Drug Metabolism in the Body

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Photo by Rens D on Unsplash

Cinnamon is one of the oldest and most commonly used spices in the world – but a new study from the University of Mississippi indicates a compound in it could interfere with some prescription medications.

In a recent study published in Food Chemistry: Molecular Sciences, the researchers found that cinnamaldehyde, a primary component of cinnamon, activates receptors that control the metabolic clearance of medication from the body, meaning consuming large amounts of cinnamon could reduce the effects of drugs.

“Health concerns could arise if excessive amounts of supplements are consumed without the knowledge of health care provider or prescriber of the medications,” said Shabana Khan, a principal scientist in the natural products centre. “Overconsumption of supplements could lead to a rapid clearance of the prescription medicine from the body, and that could result in making the medicine less effective.”

Aside from its culinary uses, cinnamon has a long history of being used in traditional medicine and can help manage blood sugar and heart health and reduce inflammation. But how the product actually functions in the body remains unclear.

Sprinkling cinnamon on your morning coffee is unlikely to cause an issue, but using highly concentrated cinnamon as a dietary supplement might.

“Despite its vast uses, very few reports were available to describe the fate of its major component – cinnamaldehyde,” Khan said. “Understanding its bioaccessibility, metabolism and interaction with xenobiotic receptors was important to evaluate how excess intake of cinnamon would affect the prescription drugs if taken at the same time.”

Not all cinnamon is equal. Cinnamon oil – which is commonly used topically as an antifungal or antibacterial and as a flavouring agent in food and drinks – presents almost no risk of herb-drug interactions, said Amar Chittiboyina, the center’s associate director.

But cinnamon bark – especially Cassia cinnamon, a cheaper variety of cinnamon that originates in southern China – contains high levels of coumarin, a blood thinner, compared to other cinnamon varieties. Ground Cassia cinnamon bark is what is normally found in grocery stores.

“In contrast, true cinnamon from Sri Lanka carries a lower risk due to its reduced coumarin content,” he said. “Coumarin’s anticoagulant properties can be hazardous for individuals on blood thinners.”

More research is needed to fully understand the role that cinnamon plays in the body and what potential herb-drug interactions may occur, said Bill Gurley, a principal scientist in the Ole Miss center and co-author of the study.

“We know there’s a potential for cinnamaldehyde to activate these receptors that can pose a risk for drug interactions,” he said. “That’s what could happen, but we won’t know exactly what will happen until we do a clinical study.”

Until those studies are complete, the researchers recommend anyone interested in using cinnamon as a dietary supplement to check with their doctor first.

“People who suffer from chronic diseases – like hypertension, diabetes, cancer, arthritis, asthma, obesity, HIV, AIDS or depression – should be cautious when using cinnamon or any other supplements,” Khan said. “Our best advice is to talk to a health care provider before using any supplements along with the prescription medicine.

“By definition, supplements are not meant to treat, cure or mitigate any disease.”

Source: University of Mississippi

Categories : Diet and NutritionTags :

Developing a Grapefruit that Won’t Interfere with Medication Levels

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Photo by Olga Petnyunene on Unsplash

Grapefruit and pummelo contain compounds called furanocoumarins that may affect the blood levels of more than 100 prescription drugs, so that people taking these medications are advised to remove these fruits from their diets. Research published in New Phytologist reveals genetic information about the synthesis of furanocoumarins in different citrus plant tissues and species and provides new insights that could be used to develop grapefruit and pummelo that lack furanocoumarins.

The research indicates that the production of furanocoumarins in citrus fruit is dependent on the integrity of a single gene within a multi-gene cluster that encodes enzymes of the 2-oxoglutarate-dependent dioxygenase family.

“This research helps us to understand why fruit of certain citrus species produce furanocoumarins and demonstrates how breeders and researchers could develop furanocoumarin-free citrus varieties,” said co–corresponding author Yoram Eyal, PhD, of the Volcani Center, in Israel.

Source: Wiley

Categories : Lab Tests and ImagingTags :

Experimental Model Identifies New Drug–drug Interactions

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Photo by Myriam Zilles on Unsplash

When taking oral drugs, transporter proteins found on cells that line the gastrointestinal tract facilitate their entry into the bloodstream. But for many drugs, it is not known which of those transporters they use to exit the digestive tract.

Identifying the transporters used by specific drugs could help to improve patient treatment because if two drugs rely on the same transporter, they can interfere with each other and should not be prescribed together.

Researchers at MIT, Brigham and Women’s Hospital, and Duke University have developed a multipronged strategy to identify the transporters used by different drugs, which appears in Nature Biomedical Engineering. Their approach, which makes use of both tissue models and machine-learning algorithms, has already revealed that a commonly prescribed antibiotic and a blood thinner can interfere with each other.

“One of the challenges in modelling absorption is that drugs are subject to different transporters. This study is all about how we can model those interactions, which could help us make drugs safer and more efficacious, and predict potential toxicities that may have been difficult to predict until now,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.

Learning more about which transporters help drugs pass through the digestive tract could also help drug developers improve the absorbability of new drugs by adding excipients that enhance their interactions with transporters.

Former MIT postdocs Yunhua Shi and Daniel Reker are the lead authors of the study.

Drug transport

Previous studies have identified several transporters in the GI tract that help drugs pass through the intestinal lining. Three of the most commonly used, which were the focus of the new study, are BCRP, MRP2, and PgP.

For this study, Traverso and his colleagues adapted a tissue model they had developed in 2020 to measure a given drug’s absorbability. This experimental setup, based on pig intestinal tissue grown in the laboratory, can be used to systematically expose tissue to different drug formulations and measure how well they are absorbed.

To study the role of individual transporters within the tissue, the researchers used short strands of RNA called siRNA to knock down the expression of each transporter. In each section of tissue, they knocked down different combinations of transporters, which enabled them to study how each transporter interacts with many different drugs.

“There are a few roads that drugs can take through tissue, but you don’t know which road. We can close the roads separately to figure out, if we close this road, does the drug still go through? If the answer is yes, then it’s not using that road,” Traverso says.

The researchers tested 23 commonly used drugs using this system, allowing them to identify transporters used by each of those drugs. Then, they trained a machine-learning model on that data, as well as data from several drug databases. The model learned to make predictions of which drugs would interact with which transporters, based on similarities between the chemical structures of the drugs.

Using this model, the researchers analysed a new set of 28 currently used drugs, as well as 1595 experimental drugs. This screen yielded nearly 2 million predictions of potential drug interactions. Among them was the prediction that doxycycline, an antibiotic, could interact with warfarin, a commonly prescribed blood-thinner. Doxycycline was also predicted to interact with digoxin, which is used to treat heart failure, levetiracetam, an antiseizure medication, and tacrolimus, an immunosuppressant.

Identifying interactions

To test those predictions, the researchers looked at data from about 50 patients who had been taking one of those three drugs when they were prescribed doxycycline. This data, which came from a patient database at Massachusetts General Hospital and Brigham and Women’s Hospital, showed that when doxycycline was given to patients already taking warfarin, the level of warfarin in the patients’ bloodstream went up, then went back down again after they stopped taking doxycycline.

That data also confirmed the model’s predictions that the absorption of doxycycline is affected by digoxin, levetiracetam, and tacrolimus. Only one of those drugs, tacrolimus, had been previously suspected to interact with doxycycline.

“These are drugs that are commonly used, and we are the first to predict this interaction using this accelerated in silico and in vitro model,” Traverso says. “This kind of approach gives you the ability to understand the potential safety implications of giving these drugs together.”

Source: Massachusetts Institute of Technology

Categories : Medical Research & TechnologyTags :

Cannabis Use Risks Harmful Drug–Drug Interactions

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Using cannabis alongside other drugs may come with a significant risk of harmful drug-drug interactions, according to a pair of new studies in the journal Drug Metabolism and Disposition.

The researchers examined cannabinoids and their major metabolites found in the blood of cannabis users and found that they interfere with two families of enzymes that help metabolise a wide range of prescription drugs. Because of this, the drugs’ effectiveness might decrease or their negative effects might increase with too much building up in the body, causing unintended side effects such as toxicity or accidental overdose.

The authors note that despite the early stage of this research, it is important to be careful when using cannabis with other prescription drugs.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Professor Philip Lazarus, senior author on the papers. “It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

One study focused on a family of enzymes known as cytochrome P450s (CYPs), whereas the other looked at UDP-glucuronosyltransferases (UGTs), another enzyme family. Together, these two enzyme families help metabolise and eliminate more than 70% of the most commonly used drugs from the body.

While some previous research focused on potential drug interactions caused by cannabinoids, this new research provides the first known comprehensive look at the interaction between three of the most abundant cannabinoids (tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN)) and their metabolites and all of the major CYP enzymes. This is also the first known research that looked for interactions between these cannabinoids and UGT enzymes, specifically.

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin. “The metabolites that result from that process stay in your body for much longer – up to 14 days – and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.”

Using human kidney cells, they found that cannabinoids and the major THC metabolites strongly inhibited several CYP enzymes. One key discovery was that one of the most abundant THC metabolites, called THC-COO-Gluc seems to play a major role in inhibiting several key enzymes in the liver. Looking at the UGT enzyme family, the researchers found that all three cannabinoids, but especially CBD, inhibited two of the primary UGT enzymes present in the liver. CBD was also found to block three enzymes that account for about 95 percent of kidney UGT metabolism, which helps clear toxins and certain drugs from the body.

“If you have a kidney disease or you are taking one or more drugs that are metabolised primarily through the kidney and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” Prof Lazarus said.

Nasrin added that these interactions between CBD and UGT enzymes could be inhibiting kidney function in patients with acute kidney disease or kidney cancer, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” Nasrin said. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”

Source: Washington State University