Towards Safer Drug Treatment
and Enhanced Patient Empowerment

Understanding Polymedication and Drug Interactions

  • What is polymedication?

    Polymedication is when a patient receives five or more medications at the same time [1]. This can be the case when a patient suffers from multiple diseases, which is also known as multimorbidity. For example, a patient could suffer from diabetes and increased blood pressure and have a bacterial infection. Here, treatment with multiple different drugs cannot be avoided. Around 26—40% of elderly European citizens receive polymedicated treatment [2]. Although polymedication is necessary in this case, it increases the risk of drug interactions and adverse drug reactions.


  • How do drug interactions work?

    Drug interactions occur when the effect and behaviour of a drug are influenced, for example, by another drug that the patient is taking or by the patient’s genetics. A drug that is affected by another drug interaction is called a “victim drug”. Overall, drug interactions can be classified in different groups:

    • Drug-drug interaction: If two or more drugs are administered at the same time, they can influence each other. The risk of this interaction increases the more drugs a patient takes. Drug interactions can occur at different sites of the human body. For example, a drug may hinder the transport of the victim drug from the intestines into the blood. Also, it may impact the breakdown of the victim drug in the liver or its elimination in the kidney.
    • Drug-gene interaction: The behaviour of a victim drug is impacted by the genetic background of the patient. For instance, depending on the individual genetic constitution of a patient, the drug may be transported quicker from the intestines into the blood or it may be broken down faster or slower in the liver.
    • Drug-drug-gene interaction: Drug-drug interactions and drug-gene interactions can also occur at the same time. As both types of interaction can affect the victim drug differently, drug-drug-gene interactions are really complex and the overall effect on the victim drug cannot be easily assessed. Depending on the mode of interaction, the level of intensity of the drug in the body may vary, which will consequently result in either a stronger effect, a weaker effect, or loss of effect of the drug, possibly causing undesired side effects.

    But how do drug interactions actually work? Drug interactions mainly affect two entities in the human cell: enzymes and transporters.

    • Enzymes: Drugs are often broken down with the help of enzymes, that can be found mainly in the liver. Similar to a nutcracker, the drug sits inside the enzyme, it is broken down and the broken parts are released. There are various different enzymes and a specific enzyme cannot break down all drugs as some do not fit inside. This is the reason why drug interactions affect each victim drug differently. Some drugs (so-called perpetrators) can block the enzyme and slow down its activity, other drugs may speed it up. The baseline activity of enzymes depends on the genetic constitution of the patient. Some people may have slower working enzymes or enzymes that do not work at all, while others may have more enzymes that work faster.
    • Transporters: Transporters are small tunnels that help transport the drug throughout the body. They are mainly localised at three important barriers in the body: At the brain barrier, they limit the uptake of substances that may be harmful for the brain. In the intestine, they support the uptake of nutrients from the gut into the body or limit the uptake of drugs. Lastly, in the kidney, they tunnel drugs into the urine. There are different kinds of transporters and one transporter cannot transport all forms of drugs since not all drugs fit through the tunnel. Some drugs may also block the transporter, causing the victim drug not to be tunneled into the cells. Depending on a person’s genetics, the cells of different patients can have more or less of these transporters so that more or less of the drug can be transported. Genetics can also result in a differently shaped transporter, which is why some drugs cannot be effectively transported in some patients.
  • What are common types of adverse drug reactions?

    Therapy of diseases with medicines is important and necessary. Frequently, therapy with more than one drug is required and inevitable. Medicines can lead to side effects and also unintended adverse drug reactions (ADRs). Here, one can distinguish between different types of ADRs. On the one hand, a person may have an allergic reaction to a drug and on the other hand, ADRs can be related to the amount of drug in the body. For example, a lack of therapeutic effect can occur if the drug level is too low, while the effect can be too strong, or side effects can occur if the drug level is too high [3,4]. The intensity of a drug in the body can be altered by drug interactions (refer to “How do drug interactions work”) or due to the condition of the patient. If, for example, a patient’s kidney is impaired, the drug is excreted slower, resulting in higher drug levels. Physicians or pharmacists should be consulted if an adverse drug reaction is observed.


  • How are polymedication, drug interactions and ADRs managed in current clinical practice ?

    Healthcare professionals, including physicians or pharmacists, contribute to the management of polymedication and drug interactions. For example, drug interactions are tested during drug development, and prescribing information lists potential drug interactions alongside the risks of ADRs. In combination with Tools assessing a drug’s potential for drug interactions and ADRs can help physicians and pharmacists check a patient’s medication. In some European countries, pharmacies offer medication checks to screen the whole medication of a patient for potential drug interactions and if the medication is well tolerated by the patient. Based on the results, the medication of a patient may be adjusted and improved. Currently, these services are not well promoted, however, thus most patients do not know about the possibility of a professional medication check or are not aware of the fact that a medication analysis would be useful in their case.

    Moreover, therapeutic drug monitoring can help increase the tolerability of drug therapy. For several drugs that for instance influence blood clotting, regular blood tests are performed to monitor their effect. When a drug interaction is identified, a patient’s medication can be adapted or the drug in question can be changed to a more suitable therapy.