What might happen when you take lots of medicines...
One of our uncles died of liver cirrhosis ten years back. He never touched alcohol in his life. He didn't have any viral infection to cause this. He didn't have diabetes, heart problems and he was not obese. Actually there was no reason that doctors could identify that might have caused this condition in him.
But, when they learned that he took lots and lots of medicines even for small ailments like headaches, stomachaches, sleeplessness, they realized reaction to drugs could have caused his condition. He used to take them even as a preventive measure in anticipation of health conditions! Because he was a medical store in-charge of a hospital and he had almost all the medicines at his disposal! I still remember the big blue plastic box in his cupboard he used to keep his medicines in.
My mother used to suffer from several ailments. Diabetes ( sometimes hypoglycemia) , BP, arthritis, osteoporosis, bronchial asthma, oedema, severe anemia, indigestion, sciatica, fungal infection of fingers and toes because of diabetes despite taking several precautions, frequent lung, dental and other infections, weakness because of old age, irregular heart beat, pericardial effusion and in the end brain stroke.
Doctors used to prescribe lots of medicines for her*. One body, multiple drugs: It can be a recipe for disaster! The risk increases with age. And my mother was old and frail! I used to wonder what might happen if she took several medicines for all those conditions mentioned above. I even discussed this with doctors and pleaded with them to prescribe medicines for her only if they're absolutely necessary. I used to ask them to tell me what they were prescribing and why she needed them. And I gave her medicines only that were necessary for her survival.
*When a person 's prescribed several different medications at once in order to treat one or multiple health conditions—the phenomenon is known as polypharmacy. (4)
While giving all those medicines to her ... these things crossed my mind several times...
These are chemicals! Although tested for human safety, clinical researchers usually weigh pros and cons and select the ones whose positives outweigh negatives. But still there will be negatives - what we call side effects. Despite these ill effects we use them because they are necessary for the survival of patients or to prolong their lives. Taking medicines or drugs is a necessary evil in such cases!
And the most important thoughts that disturbed me were ... when people take several medicines like my mother used to ... they can ...
1. Interact with one another
2. produce over dose of a drug because too much of one drug remains in your system because of the interactions
2. reduce or increase the potency of one another if they act in opposite or similar ways
3. nullify one another's potency if one drug can’t be absorbed or metabolized properly
4. produce other toxic and harmful products after reacting with one another inside human bodies
5. interfere with the patient's normal metabolic processes
6. cause damage to body organs
7. cause several other severe health conditions as a result of the above processes
-and this one is a positive one-
8. successfully suppress an existing health condition and help us find a new cure for diseases that don't have medicines yet!
These thoughts of mine have solid base as I know about the research going on in the clinical field ( now I can understand why they say ignorance is a bliss. At least you don't have to worry about these things in the beginning and can have mental peace but only up to a certain extent. When once you and your family members and friends start suffering severely because of your ignorance, the saying sails out through the window . Although we worry a lot because of the knowledge we have, we can take precautions and keep ourselves and our loved ones safe for a long time ).
Interactions can vary from person to person because of changes in the absorption, distribution, metabolism, gut microbes and excretion of the drug within the body. Because of this, drug reactions largely are unpredictable, even with known interactions.
There are hundreds of possible interactions between commonly prescribed medicines that very few people seem to have heard of. People routinely use these medicines, without much thought because, well, they are medicines and are suppose to cure their ailments! Not enhance them. But unfortunately sometimes they do just the second one as a result of drug interactions! So why do they happen, and why do they matter? The drug interactions happen mostly because of competition!
Some drugs work in complementary or opposite ways at the same sites in the body. If they're given together, they can compete with each other, reducing (or sometimes increasing) the effect of one or both. A good example is the beta-blocker, which is given to people who've had a heart attack or heart failure, or sometimes high blood pressure. If you have asthma, one of the main treatments is an inhaler called a beta agonist (commonly called Ventolin or salbutamol). A beta agonist makes the beta receptors in your body work better - a beta-blocker stops them. If you have asthma, some beta-blockers can bring on an asthma attack or stop your inhaler from working.
Most medicines you take as tablets get into your bloodstream. After a few hours, they're removed through your kidneys or your liver, which act as filters not just for medicines but for all sorts to toxins and products your body makes. Your kidneys and liver are incredibly complicated organs, with hundreds of different chemicals called enzymes working all the time to stop toxins from building up in your body. If two medicines are broken down by the same enzymes, they can interact. That means that, for instance, if you're taking a statin tablet called simvastatin, you shouldn't also take antibiotics like erythromycin or heart tablets called diltiazem, verapamil and amiodarone. Bizarrely, even drinking grapefruit juice can affect how simvastatin is broken down, so taking the two together can lead to dangerously high levels of simvastatin in your system.
Another danger is, if the side effects are similar, they can add up. For example, if you take allopurinol (Lopurin or Zyloprim) for gout and add the drug azathioprine (Imuran) to treat rheumatoid arthritis, the azathioprine can further suppress your immune system, possibly putting you at risk of a serious infection. And, both aspirin and the blood-thinning drug warfarin (Coumadin) decrease your blood's ability to clot, so if you're taking warfarin for cardiovascular disease and aspirin to ease your migraine problem, you could be unknowingly going for a life-threatening bleeding episode!
Sildenafil (viagra) and Nitrate (sorbitrate) tend to cross-react and can create hypotension (BP fall) they are pharmacologically contraindicated as combination.
And - this is very important - many herbal products and medicines from your alternate medicine kits can interact with other medicines. These include 'natural' remedies for depression.
Moreover if you take alcohol or some vitamin and food supplements, they too might interfere with the medicines' potency and sometimes can cause severe toxic effects and even death!
Alcohol often has harmful interactions with prescription medications, over-the-counter drugs, and even some herbal remedies. Alcohol interactions with medications may cause problems such as:
nausea and vomiting, headaches, drowsiness, dizziness, fainting, changes in blood pressure, abnormal behavior, loss of coordination and accidents. Mixing alcohol and medications also may increase the risk of complications such as:
liver damage, heart problems, internal bleeding, impaired breathing and depression.
In some cases, alcohol interactions may decrease the effectiveness of medications or render them useless. In other cases, alcohol interactions may make drugs harmful or even toxic to the body.
Even in small amounts, alcohol also may intensify medication side effects such as sleepiness, drowsiness, and light-headedness, which may interfere with your concentration and ability to operate machinery or drive a vehicle, and lead to serious or even fatal accidents.
Hundreds of commonly used prescription and over-the-counter drugs may adversely interact with alcohol. These include medications used for: Allergies, colds, and flu, angina and coronary heart disease, anxiety and epilepsy, arthritis, blood clots, cough, depression, diabetes, enlarged prostate, heartburn and indigestion, high blood pressure, high cholesterol, infections, muscle pain, nausea and motion sickness, pain, fever, and inflammation, seizures, severe pain from injury, post-surgical care, oral surgery, migraine and sleep problems.
Alcohol is metabolized in the liver, and a lot of drugs are metabolized via the same pathways. So it has the potential to interact with a whole host of drugs, including things you might not think are related at all.
One should never drink while on antibiotic treatment.
Certain dietary supplements can change absorption, metabolism, or excretion of a medication and therefore affect its potency. You may be getting either too much or too little of a medication you need if you take these supplements. Dietary supplements are widely used by people and include vitamins, minerals, and other less familiar substances—such as herbals, botanicals, amino acids, and enzymes. Children are more vulnerable in case of drug and supplement interactions.
Natural does not always mean safe. For example, many weight loss products claim to be “all-natural” or “herbal,” but their ingredients may interact with medications or may be dangerous for people with certain medical conditions.
My mother used to take several ayurved medicines prescribed by well qualified ayurved doctors for her knee problems. Some 15 years back she developed severe diabetes with her blood sugar levels going up to 500 - 600 mg/dL. The main stream doctors when consulted asked us about the medicines she was taking. When told about the ayurvedic medicines, they asked us to immediately stop using them. They told us some of them contain steroids that enhance the diabetic conditions several fold if people are vulnerable and genetically predisposed to them.
Warfarin (a prescription blood thinner), ginkgo biloba (a herbal supplement), aspirin and vitamin E (a supplement) can each thin the blood. Taking any of these products together may increase the potential for internal bleeding or stroke.
Antibiotics can limit body's ability to uptake analgesics: Disruption of the microbiota, whether induced by dietary changes, antibiotic administration or invasive pathogens, can disturb the balance of the microbiota and alter metabolic networks. These disturbances can affect the biodisposition of certain drugs, which can ultimately lead to adverse drug reactions (2). There are many diverse mechanisms the gut microbiome can use to alter the disposition, efficacy and toxicity of drugs and foreign substances. These can include the expression of enzymes that can activate or inactivate drugs, the direct binding of drugs to a bacterial organism, the reactivation of drugs by microbial expressed enzymes, and the direct competition between the host and microbes for host metabolizing enzymes. For example, an association between pre-dose, gut-derived urinary metabolites and response to the commonly used analgesic acetaminophen has been reported. Research results suggest that exposure to amoxicillin or ampicillin/neomycin can alter the pharmacokinetics and metabolism of acetaminophen, and that these alterations could be due to changes in gut microbiome composition. Shifts in the composition of gut microbiota can disturb the balance of organisms, which can influence the biodisposition of orally administered drugs (3).
Grapefruit juice can be part of a healthful diet—most of the time. It has vitamin C and potassium—substances your body needs to work properly. But it isn’t good for you when it affects the way your medicines work. Grapefruit juice and fresh grapefruit can interfere with the action of some prescription drugs, as well as a few non-prescription drugs. This interaction can be dangerous. With most drugs that interact with grapefruit juice, the juice increases the absorption of the drug into the bloodstream. When there is a higher concentration of a drug, you tend to have more adverse events. For example, if you drink a lot of grapefruit juice while taking certain statin drugs to lower cholesterol, too much of the drug may stay in your body, increasing your risk for liver damage and muscle breakdown that can lead to kidney failure. Drinking grapefruit juice several hours before or several hours after you take your medicine may still be dangerous. So it’s best to avoid or limit consuming grapefruit juice or fresh grapefruit when taking certain drugs. While scientists have known for several decades that grapefruit juice can cause a potentially toxic level of certain drugs in the body, more recent studies have found that the juice has the opposite effect on a few other drugs.
Examples of some types of drugs that grapefruit juice can interact with are:
some statin drugs to lower cholesterol, such as Zocor (simvastatin), Lipitor (atorvastatin) and Pravachol (pravastatin) some blood pressure-lowering drugs, such as Nifediac and Afeditab (both nifedipine) some organ transplant rejection drugs, such as Sandimmune and Neoral (both cyclosporine) some anti-anxiety drugs, such as BuSpar (buspirone) some anti-arrhythmia drugs, such as Cordarone and Nexterone (both amiodarone) some antihistamines, such as Allegra (fexofenadine) Grapefruit juice does not affect all the drugs in the categories above. Ask your health care professional to find out if your specific drug is affected.
The opposite effect grape fruit juice can have on drugs is important too. It involves the transportation of drugs within the body rather than their metabolism, according to doctors. Proteins in the body known as drug transporters help move a drug into cells for absorption. Substances in grapefruit juice block the action of a specific group of transporters. As a result, less of the drug is absorbed and it may be ineffective.
(Don't confuse grape fruit with grapes - some people who read this article have asked me whether they have to stop eating grapes while taking medicines. The grapefruit is a subtropical citrus tree known for its sour to semi-sweet fruit. Grapefruit is a hybrid originating in Barbados as an accidental cross between two introduced species, sweet orange. I am adding pictures of grape fruit and grapes to help you distinguish between the two types of fruits.
Grape fruit
Grapes
So what can you do now after learning about these things? Discuss with doctors! Stick to one doctor, if possible, who knows your complete health profile and the medicines you are taking..
When you're getting a new medicine from your doctors, tell them about all the medicines you're using. Don't fail to recall and let them know about medicine changes from hospital clinics, dentists etc. And don't forget to mention medicines you get without prescription - even paracetamol or aspirin. That way, your healthcare professional can assess the situation properly and reassure you that they're safe to take together.
Many medicines now come with a patient information leaflet, which should tell you about and other medicines yours might interact with.
Adjust the timing. Some medications interfere with others by keeping the second one from being absorbed in the intestine. For example, antacids can interfere with the body's absorption of tetracycline and some other antibiotics. In those cases, just adjusting the timing a bit will alleviate the problem.
Change the dose – or the drug. Sometimes two drugs interact to increase or decrease the effectiveness of the other. Nonsteroidal anti-inflammatory drugs, for example, can blunt the effects of drugs that treat high blood pressure, sometimes making it necessary to increase the dose of the blood pressure medication. If a drug increases the effect of another, lowering the dose of one may help. In other cases, your doctor can switch you to a different drug that provides the benefits without the interaction risk (4).
Monitor closely. In some cases you need all the drugs you are taking, even if they have the potential to interact. When that happens, your doctor will need to monitor you closely, usually through frequent blood tests. Unless a problem is detected, the risk of taking you off a medication – or perhaps even changing the dose – may be worse than the risk of interactions in such situations.
Although this is usually the choice of last resort, doctors must sometimes prescribe a third medication to help alleviate the problems that an interaction between two other drugs is causing! For example, if you need both NSAIDs (non-steroidal anti-inflammatory drugs, also known as NAIDs, non-steroidal anti-inflammatory agents/analgesics) and corticosteroids, yet taking them together causes stomach upset or increases your risk of developing a stomach ulcer, your doctor may prescribe a third drug to ease your stomach upset and reduce your ulcer risk.
The best thing to do is ... please don't take medicines unless they are absolutely necessary and unless your doctor stresses the need to take them. I don't too! And strictly stick to your doctor's advice. Don't tread the path of misadventures by following what your friends, neighbours and relatives suggest if they are not qualified to give you guidance on health issues.
One more thing: gut microbes may contribute to the dramatic variability that is observed in side effects and efficacy between different patients (1). So what we see in labs is not seen inside human bodies making things very complicated.
Watch this video that confirms exactly what I said above:
3. Michael A. Malfatti et al. Manipulation of the Gut Microbiome Alters Acetaminophen Biodisposition in Mice, Scientific Reports (2020). DOI: 10.1038/s41598-020-60982-8
Any drug that is taken orally must pass through the lining of the digestive tract. Transporter proteins found on cells that line the GI tract help with this process, but for many drugs, it's 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 have now developed a multipronged strategy to identify the transporters used by different drugs. 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 modeling 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.
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.
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 analyzed a new set of 28 currently used drugs, as well as 1,595 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.
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.
In addition to identifying potential interactions between drugs that are already in use, this approach could also be applied to drugs now in development. Using this technology, drug developers could tune the formulation of new drug molecules to prevent interactions with other drugs or improve their absorbability.
Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning, Nature Biomedical Engineering (2024). DOI: 10.1038/s41551-023-01128-9
Identifying Chemicals in Our Environment Could Help Medicines Work Better
Gary W. Miller
Your genesplay a major rolein determining your height, hair and eye color, and skin tone, but they don't tell the entire story of who you are.
Your environment is incredibly important in shaping your personality, your likes and dislikes, and your health. In fact, your diet, social interactions, exposure to pollution, physical activity and education oftenexceed the influence of geneticson many of the features that define you.
Figuring out how your genes and environment increase your likelihood of developing asthma, heart disease,cancer, dementia and other conditions can have life-changing consequences.
The field of genomics has made it relatively straightforward to test both in the hospitaland at homefor a wide range of genetic variations linked to disease risk.
And in recent years, science has been making progress on tracking down theenvironmental culpritsthat drive risk for several diseases – and on identifying ways to optimize treatments based on your personal environmental exposures.
While your genome comprises all of the genes that encode your biology, your exposome is a concept that comprises all your environmental exposures. Like how researchers use DNA sequencers to study genomics, scientists in exposomics use chemistry and high-tech sensors to measure the effects of thousands of environmental factors on health.
Medications don't always work
For many people, standard drug therapies to treat certain conditions simply don't work. Controllingblood pressureoften requires months of trial and error. It can take months or even years to identify an adequate treatment planfor depression.
Adverse events caused by medications account formore than 1 millionvisits to emergency departments each year in the US.
What drives these differences in drug effects between patients? Is it their genes? Are they not taking their medication as prescribed due to side effects? Or something else?
As it turns out, your environment can have a major effect on how well specific treatments work for you. Think about the warning labels advising you not to drink grapefruit juice while taking a specific drug, for example.
This is because a natural chemical in grapefruit inhibits theenzymes that break downthose medications. Some common statins used to control high cholesterol can build up to toxic levels because the chemical in grapefruit juice blocks its normal processing.
Grapefruit isn't the only environmental factor affecting how you respond to your medications.Over 8,600 chemicalsare used in commerce in the US, and you are exposed to thousands of these chemicals on a daily basis. It is more likely than not that many of these chemicals can interact with the drugs you take.
Some of the chemicals we use to keep fleas and ticks off pets can actuallyincrease the levelsof the same enzyme blocked by grapefruit juice, meaning a statin may be broken down so fast that it doesn't control elevated cholesterol.
Byproducts from the combustionof organic matter, such as engine exhaust and burning wood, can also interfere with drug-metabolizing enzymes.
Some of these chemicals, calledpolyaromatic hydrocarbons, can inactivate medications used to treat asthma. The environmental factor triggering your asthma could prevent the drugs used to treat it from working.
A chemical solution?
Advances in chemistry are helping researchers figure out what chemicals are getting in the way of treatment.
Yourhospital laboratorycan already measure dozens of molecules in your blood. Measuring your salt levels can tell doctors how your kidneys are working, cholesterol levels indicate your risk of heart disease, and specific enzymes reveal your liver's health. These common tests are routine and useful for nearly every patient.
There are many additional tests that can help determine how a specific condition is progressing or responding to therapy.Hemoglobin A1c levelshelp determine how well glucose levels are being controlled in those with prediabetes ordiabetes. And thousands of other human diseases have their owncorresponding biomarkers.
In research laboratories, scientists can detect the presence of thousands of molecules at once using instruments calledmass spectrometers. Each chemical in a sample has a unique mass, and these devices measure these masses for scientists to categorize.
Thus, scientists can identify all of the pesticides, plasticizers, plastics, pollution and other chemicals present in a given sample. They can also measure your own internal biology, such as the compounds involved in processing the food you eat and the hormones influencing how you behave.
Moreover, mass spectrometers canmeasure drug metabolites. When you take a drug, it is typically broken down or metabolized to several different compounds.
Some of these compounds contribute to the drug's effects, while others are inactive. Analyzing what metabolites are present in your body provides information about how you process drugs and whether the drugs you're taking will interact with each other.
Taking all these factors together, scientists can study how your environment may be interfering with the effectiveness of your medications.
A better prescription – for you
Together with dozens of scientists across many institutions, my colleagues and I are developing methods to measure all of the chemicals in your body.
The project,dubbed IndiPHARM– short for individualized pharmacology – is designing tools to measure a wide range of drugs, drug metabolites and environmental chemicals at the same time.
By combining environmental data with genetic information, we hope to improve how drugs work in people by figuring out whether chemicals in their environment or diet are altering how they process a given drug.
This includes whether the administered drugs are at therapeutic levels, how the drugs and chemicals are interacting with each other, and determining whether other variables are affecting intended drug effects.
This could lead to changing the amount of drug prescribed, switching to a different medication or even redesigning the medicines themselves.
Our team is starting with identifying the environmental and biological factors associated with metabolic diseases, including obesity and diabetes, along with common co-occurring conditions such as hypertension, high cholesterol anddepression.
For example, there aresignificant differencesin how well people respond to anti-obesity or anti-diabetes drugs, and we hope to figure out why that is so all patients can benefit through tailored treatment.
Getting the right drug to the right person at the right time requires a better understanding of the environmental factors that influence how they work.
We envision a future where a doctor can use your genetic and environmental history to figure out the best drug treatment that would work for you from the start, reducing the need for trial and error.