Why prescription drugs may work differently for different people

Different people taking the same medicine can have very different responses to the same dose. While many people will get the desired effects, some may get little or no benefit from it, and others may have unwanted side effects.

As a pharmacist who researches the safety and effectiveness of drugs, I know this happens for a number of reasons, including individual physical differences, drug interactions, and inflammation.

Genetic differences

The liver has a collection of enzymes called the cytochrome P450 system that metabolize or break down many drugs so that they can be eliminated from the body.

The DNA, or genetic material, of cells contains the blueprint for how these enzymes are created. Unfortunately, some people have small errors in their DNA called polymorphisms that result in enzymes that don’t work as well.

C. Michael White. (Sean Flynn / UConn Photo)

Where these errors appear in the enzymatic material. If they occur in parts of the enzyme that are not directly involved in breaking down the drug, they will have little effect on how you metabolize a drug. However, errors affecting the active site of the enzyme that binds to drugs can cripple its ability to break down a drug and subsequently mean that there is more of the drug circulating in the blood. If the increasing blood concentration exceeds the therapeutic range of the drug, serious side effects may occur.

Some people have a polymorphism that requires their body to create two of the same enzyme instead of just one. These “ultrametabolizers” break down drugs faster than normal, resulting in a lower concentration of the active drug in their body. If the concentration falls below the therapeutic range, there may not be enough drug for a beneficial effect.

Clinicians can test patient DNA for these enzyme polymorphisms. If a known polymorphism is detected, they may change the dose or avoid certain drugs altogether if they don’t work as well as they should or are more likely to cause side effects.

Drugs interactions

Genetic variability explains only part of the variability of the drug response. Another factor to consider is drug interactions.

Some drugs block the active site of the liver enzyme cytochrome P450 so that it cannot be reused, preventing other drugs from binding and metabolizing to it. As drug concentrations increase, the risk of side effects also increases. For example, amiodarone, a heart rhythm medicine, can block the metabolism of the anticoagulant warfarin, resulting in very high concentrations of warfarin which can lead to life-threatening bleeding.

Conversely, the antiepileptic drugs phenytoin and carbamazepine may stimulate the production of even more metabolic enzymes than usual. Other drugs may be metabolized faster than usual and their beneficial effects may be lost.


When the body is newly infected or injured, the inflammatory response brings white blood cells and increased blood flow to the area to sterilize and repair the problem. The inflammation is believed to last only for short periods of time. But some people’s immune systems can also attack unaffected areas and lead to chronic inflammation that can damage tissues and joints, and even increase the risk of heart disease.

Inflammation from a new infection or from a chronic inflammatory disease like rheumatoid arthritis or psoriasis could also affect the ability of enzymes like cytochrome P450 to metabolize drugs.

In addition to producing cytochrome P450 enzymes, the liver is one of the main organs that create special proteins called cytokines and interferons that are involved in the immune response. When the liver is busy making all of these proteins, it does not have the capacity to make as many drug metabolizing enzymes, resulting in decreased drug breakdown. When the infection goes away or the source of the inflammation is blocked by anti-inflammatory drugs, the liver’s ability to metabolize the drugs returns to normal. This means that a person with a chronic infection or inflammation may need a lower than normal dose of the medicine because their liver enzymes do not clear them as quickly as usual. And when this inflammation resolves, they may need to increase their dose to maintain the same desired effects they had before.

One of the best ways to see if you have increased inflammation is to check your C-reactive protein (CRP) concentration. Although CRP does not directly cause inflammation, the body produces more CRP due to inflammation. Thus, a higher CRP level in the blood could indicate an underlying inflammation and, subsequently, an increased suppression of drug metabolism.

Other factors affecting drug metabolism

Even if drug interactions are avoided and inflammation is under control, many other factors can influence the effects of drugs.

Damage to the liver or kidneys may reduce the breakdown of drugs and possibly their expulsion in the urine or bile.

The size of the body also affects the response to the drug. The concentration of the drug in the body is determined both by the administered dose and by the volume of bodily fluids of an individual. Giving the same dose of medicine to a shorter person could result in a higher blood level than when given to a taller person. For this reason, many drugs are given in lower doses to children than to adults.

And finally, some people don’t have a lot of receptors in their body for the drug to bind and work, or the receptors they do have don’t work well. It could be due to genetic mutations or an underlying disease. An average dose of a drug would produce only a limited response in these patients.

Talk to your clinician

One of the reasons that there are so many types of drugs and doses available for different conditions is that your response to the drug may not be the same as the average person. When you start a new drug regimen it may need to be adjusted to the right level, which will require patience and cooperation between you and your clinician.

To identify any potential drug interactions, tell your pharmacist about all prescription, over-the-counter, and dietary supplements you take.

If you develop a new infection or disease that causes inflammation, the doses of other medicines you are currently taking may need to be reduced. If you notice any new side effects, tell your clinician or pharmacist immediately.

If you have a severe chronic inflammatory disease like rheumatoid arthritis or psoriasis and you start a strong anti-inflammatory drug, tell your clinician or pharmacist if other medicines you are taking are not working as well as before so that your dose may be adjusted. .

Originally published in The Conversation.

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About Alex S. Crone

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