{"id":177980,"date":"2021-10-13T07:00:43","date_gmt":"2021-10-13T11:00:43","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=177980"},"modified":"2021-10-06T15:30:21","modified_gmt":"2021-10-06T19:30:21","slug":"why-prescription-drugs-can-work-differently-for-different-people-2","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2021\/10\/why-prescription-drugs-can-work-differently-for-different-people-2\/","title":{"rendered":"Why Prescription Drugs Can Work Differently for Different People"},"content":{"rendered":"

Different people taking the same drug can have\u00a0markedly different responses<\/a>\u00a0to the same dose. While many people will get the intended effects, some may get little to no benefit, and others may get unwanted side effects.<\/p>\n

As a\u00a0pharmacist<\/a>\u00a0who\u00a0researches the safety and effectiveness of drugs<\/a>, I know there are several reasons why this occurs, including individual physical differences, drug interactions and\u00a0inflammation<\/a>.<\/p>\n

Genetic Differences<\/strong><\/p>\n

The liver has a collection of enzymes called the\u00a0cytochrome P450<\/a>\u00a0system that metabolize, or break down, many drugs so they can be removed from the body.<\/p>\n

The DNA, or genetic material, of cells contain the blueprint on how to create these enzymes. Unfortunately, some people have small errors in their DNA called\u00a0polymorphisms<\/a>\u00a0that result in enzymes that don\u2019t work as well.<\/p>\n

\"C.
C. Michael White. (Sean Flynn\/UConn Photo)<\/figcaption><\/figure>\n

Where these errors<\/a>\u00a0show up in the enzyme matter. If they occur in parts of the enzyme that aren\u2019t directly involved in drug breakdown, they will have little effect on how well you metabolize a drug. Errors affecting the enzyme\u2019s\u00a0active site<\/a>\u00a0that binds to drugs, however, can cripple its ability to break down a drug and subsequently mean there\u2019s\u00a0more of the drug circulating in the blood<\/a>. If the rising blood concentration\u00a0exceeds the drug\u2019s therapeutic range<\/a>, serious side effects can occur.<\/p>\n

Some people have a polymorphism that instructs their body to create two of the same enzyme instead of just one. These \u201cultrametabolizers<\/a>\u201d break down drugs faster than normal, resulting in a lower concentration of active drug in their bodies. If the concentration falls below the therapeutic range, there may not be enough drug for a beneficial effect.<\/p>\n

Clinicians can test patients\u2019 DNA for these enzyme polymorphisms. If a known polymorphism is detected, they can\u00a0alter the dose<\/a>\u00a0or avoid certain drugs altogether if they don\u2019t work as well as they should or are more likely to cause side effects.<\/p>\n

Drug Interactions<\/strong><\/p>\n

Genetic variability only explains a portion of the variability in drug response. Another factor to consider is\u00a0drug interactions<\/a>.<\/p>\n

Some drugs block the active site of the liver enzyme cytochrome P450 so it can\u2019t be reused, preventing other drugs from binding to it and getting metabolized. As drug concentrations rise, so does the risk of side effects. For example, the heart rhythm drug amiodarone can block\u00a0metabolism of the blood thinner warfarin<\/a>, which results in very high warfarin concentrations that could lead to life-threatening bleeding.<\/p>\n

Conversely, the antiepilepsy drugs phenytoin and carbamazepine can\u00a0stimulate production of even more metabolic enzymes<\/a>\u00a0than usual. Other drugs may be metabolized faster than usual, and their beneficial effects may be lost.<\/p>\n

Inflammation<\/strong><\/p>\n

When the body is newly infected or injured, the\u00a0inflammatory response<\/a>\u00a0brings white blood cells and increased blood flow to the area to sterilize and repair the problem. Inflammation is meant to\u00a0last for only short periods of time<\/a>. But the immune systems of some people may also attack unaffected areas and result in chronic inflammation that can damage tissues and joints, or even increase the\u00a0risk of heart disease<\/a>.<\/p>\n

Inflammation<\/a>\u00a0from a\u00a0new infection or chronic inflammatory disease<\/a>\u00a0like rheumatoid arthritis or psoriasis could also impair how well enzymes like cytochrome P450 can metabolize drugs.<\/p>\n

In addition to producing cytochrome P450 enzymes, the liver is one of the major organs that create special proteins called\u00a0cytokines and interferons<\/a>\u00a0that participate in the\u00a0immune response<\/a>. When the liver is busy making all of these proteins, it does not have the capacity to make as many drug-metabolizing enzymes, which results in a decline in drug break down. When the infection goes away or the source of inflammation is blocked with anti-inflammatory drugs, however, the liver\u2019s ability to metabolize drugs\u00a0goes back to normal<\/a>. This means that someone with an\u00a0infection or chronic inflammation<\/a>\u00a0might need a lower dose of drug than normal since their liver enzymes aren\u2019t clearing them as quickly as usual. And when that\u00a0inflammation is resolved<\/a>, they may need to increase their dose to maintain the same desired effects they had before.<\/p>\n

One of the prime ways to see if you have increased inflammation is by checking your\u00a0c-reactive protein (CRP)<\/a>\u00a0concentration. While CRP doesn\u2019t directly cause inflammation, the body produces more CRP as a result of inflammation. So a higher CRP level in the blood could indicate underlying inflammation and, subsequently,\u00a0increased suppression<\/a>\u00a0of drug metabolism.<\/p>\n

Other Factors Affecting Drug Metabolism<\/strong><\/p>\n

Even if drug interactions are avoided and inflammation is kept in check, there are many other factors that can influence drug effects.<\/p>\n

Liver or kidney damage<\/a>\u00a0could reduce how well drugs are broken down and eventually expelled in the urine or bile.<\/p>\n

Body size also affects drug response. Drug concentration in the body is determined by both the dose given and the volume of an individual\u2019s body fluids. Giving the same drug dose to a\u00a0smaller-sized person<\/a>\u00a0could cause a higher blood concentration than when given to a larger person. This is why many drugs are given in lower doses to children than adults.<\/p>\n

And finally, some people either don\u2019t\u00a0have many receptors<\/a>\u00a0in their body for the drug to bind to and produce its effects, or the receptors that they do have don\u2019t work well. This could be due to genetic mutations or underlying disease. An average dose of a drug would only produce a limited response in these patients.<\/p>\n

Talk to Your Clinician<\/strong><\/p>\n

One reason why there are so many types of drugs and available doses for different diseases is because your response to the drug might not be the same as the average person\u2019s. When you start a new drug regimen, it might have to be adjusted to the right level, and that will take patience and cooperation between you and your clinician.<\/p>\n

To identify any potential drug interactions,\u00a0tell your pharmacist<\/a>\u00a0all the prescription, over-the-counter and dietary supplement products you are taking.<\/p>\n

If you develop a new infection or disease that causes inflammation, the dosages of the others drugs you are currently taking\u00a0might need to be reduced<\/a>. If you notice new side effects, let your clinician or pharmacist know right away.<\/p>\n

If you have a severe chronic inflammatory disease like rheumatoid arthritis or psoriasis and start a potent anti-inflammatory drug, let your clinician or pharmacist know if the other drugs you\u2019re taking\u00a0aren\u2019t working as well as before<\/a>\u00a0so your dose can be adjusted.<\/p>\n

 <\/p>\n

Originally published in The Conversation<\/a>.<\/em><\/p>\n

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