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Why Medications Affect People Differently
Why Medications Affect People Differently
The Science behind why medications work differently
The role that age, gender and general health plays
Medications are impacted by many different factors that tend to vary between people. This is why medication response can be different across individuals.
When medications are studied prior to receiving market approval, the study participants often skew towards non-elderly male adults, given inherent risks in youth, the elderly and women of child-bearing age. These studies rely on statistics they collect to prove to regulatory bodies (like Health Canada or the FDA) that they should be approved. These studies also help determine how the medication can be used (e.g., specific diagnoses, dosing regimens, monitoring details like specific blood work, etc.).
As a result, statistics built on averages and generalizations of only a representative subsection of the population are what is used to determine medications available, and how they should be used. At least initially, that is. These studies may help account for some of the differences that impact how the medication works, or they may simply restrict use when certain factors are present because the study participants weren't known to be impacted by these factors.
Factors impacting response may include liver and kidney function, as they play a role in how medications are metabolized and cleared from the body. Body weight and body fat can also influence how some medications are distributed in the body. Medical history and co-occurring medical conditions (i.e., those not being treated by the medication in question) also play a role - for example, borderline high blood pressure could spike to an uncontrolled state as a result of a side effect of a medication. The rise in blood pressure in someone with more normal blood pressure, also taking the medication, may not be a problem if they are still within an acceptable range. Age can often play a role - for example, those over the age of 65 may be more sensitive to nervous system medication side effects (like confusion or dizziness) or the effects of blood thinning medications. Female sex also tends to increase the likelihood of side effects to a wide range of medications. Hormonal changes during key points in life (e.g., pregnancy) can also affect response - it may change the benefits and side effects experienced pre-pregnancy because of a chain reaction of biochemical changes that affect medication metabolism. Even someone's "hydration status" affects response - someone not drinking enough water for their circumstances may end up being more susceptible to problematic medication side effects. This can be because not enough fluid is passing through the kidneys to ensure the medication is properly cleared from the body.
Drug interactions can also play an important role. The medication in question could interact with other prescriptions, over-the-counter products (including natural products), certain foods (e.g., grapefruit), caffeine, nicotine, cannabis and more. Interactions work in a number of ways, including changing medication absorption, metabolism, or creating opposing, additive or outsized medication effects.
Genetic factors can also play a notable role in how someone responds to medication, including side effects or whether medications are not working (or vice versa). They may even influence or add to some of the previous factors discussed. The most well-known example is how specific variations in key genes impact how fast or how slow the medication is metabolized. As a result, medication (or medication byproducts) may build up in the body and cause issues side effects, or, in other cases, be cleared from the body too quickly and not be effective at all.
Common examples of variable medication response
There are many examples of well-known or important medications whose side effects and/or effectiveness are influenced by genetics.
These include certain anti-inflammatories (including ibuprofen, meloxicam and celecoxib) when prescribed for regular, daily use. Over a week or two, genetically "slower" metabolizers are at increased risk of side effects, with changes in blood pressure and kidney function being of particular concern.
The effectiveness of many common antidepressants can be linked to "overpowered" versions of genes that influence how they are metabolized.
Many antiseizure medications are impacted by genetic variations that impact how parts of the immune system may react to use of these medications. This can contribute to major rashes that can affect a large portion of the body, which, in more severe (but rare) cases, can lead to the skin detaching from the body. Various organs may also be affected.
How pharmacogenetic testing predicts response before you start treatment
Over time, additional medication data is often collected based on the factors discussed above. This data builds on top of the original studies used to support the medication's approval and can help to create more accurate approaches to medication use, depending on the characteristics of the individual. A growing portion of this data relates to genetic testing for medication efficacy and side effects. This is known as pharmacogenetic testing.
Pharmacogenetic testing is a process involving an analysis of someone's DNA for variations known to impact side effects and/or effectiveness associated with a number of medications. This information can then be used to inform the choice of the medication selected, or the dose, monitoring, or further investigations needed when prescribers select a certain medication to improve treatment response. It can meaningfully reduce the occurrence, frequency and/or severity of side effects associated with treatments. It may even help prevent side effects with specific drugs altogether because an alternative not affected by someone's genetic variations has been selected instead. It can improve effectiveness through drug and/or dose selection. It can reduce medication trial-and-error.
What personalized prescribing means for patients
Pharmacogenetic testing provides actionable insights that can support health care providers in their medication treatment decisions. The results help identify which medications or dosing strategies may be more likely to improve effectiveness and less likely to cause problematic side effects based on their genetic profile. This allowing help reduce trial-and-error, improve treatment plan adherence, and get the most out of treatments.
