Drug interactions
By Lauren Amphlett

As we navigate our daily lives, we interact with countless other people, objects, and events, each interaction affecting us in different ways. Similarly, when we take multiple medications, they interact with each other within our bodies, sometimes in ways that can significantly change their effects. Here, we break down why some medications enhance the potency and actions of others, focusing on azole antifungal medications.

How is medication processed?

When you take a medication, it goes through a few stages in your body before it is fully processed and eliminated. This process is often referred to as ADME: Absorption, Distribution, Metabolism, and Excretion. Here’s a simplified and general explanation:

Absorption: After you take a medication, it needs to enter your bloodstream before it can reach the parts of your body where it’s needed. This usually happens in your gut, but can also occur in your lungs (if you inhale it) or your skin (if it’s a cream or patch). The speed and amount of drug absorption can depend on many factors, such as the drug’s formulation, your stomach contents, and your overall health status.

Distribution: Once the drug is absorbed into your bloodstream, it is distributed throughout your body. It may go to many different tissues and organs, or it may target a specific area. Some drugs can cross barriers in the body, like the blood-brain barrier, while others cannot.

Metabolisation (also known as Biotransformation): This is where the body starts to break down the medication. This mainly happens in the liver, where special proteins called enzymes transform the drug into different chemicals (metabolites). Some of these metabolites may be active, meaning they can also have an effect on your body, while others are inactive.

Excretion: Finally, the drug and its metabolites need to leave your body. This often happens via your kidneys, which filter out waste products into your urine. Some drugs and metabolites might also be excreted in faeces, sweat, or exhaled breath.

Throughout all of these stages, the amount of drug in your body will increase (during absorption and distribution), reach a peak, and then gradually decrease (during metabolisation and excretion). This is why most medications need to be taken regularly – to maintain the right amount of drug in your body to be effective, but not so much that it causes side effects.

Why do medications interact?

Drugs, just like people, are unique and complex. They have their own ways of working within our bodies, which we refer to as ‘mechanisms of action’. When two drugs meet in our bodies, they can influence each other’s mechanisms, causing interactions that may increase or decrease their effectiveness, or cause unexpected side effects.

Imagine our body as a busy motorway. Each drug is like a vehicle, with a specific route and destination (its target in the body). Some vehicles (drugs) may need to use the same lanes (pathways in the body), causing traffic jams or delays. Others may speed up or slow down the traffic flow, affecting the journey of other vehicles.

A quick bit about how azole antifungal medications work…

Antifungal azole medications, like itraconazole and voriconazole, are often used to treat fungal infections. To understand how they work, you first need to know a bit about fungi.

Fungi are organisms that have a hard, protective outer layer made up of something called ergosterol. This is a bit like how our skin protects us. This ergosterol is crucial for the fungus to live and grow.

Azole antifungal medications work by stopping the fungi from making ergosterol. They do this by blocking the action of an enzyme, that is essential in the production of ergosterol.

When the fungus can’t make ergosterol, it leads to holes forming in the fungal cell wall. This is a problem for the fungus because it means that its insides can leak out, and substances from the outside can get in. As a result, the fungus can’t survive.

So, in short, azole antifungals work by stopping the fungus from making a crucial component of its cell walls, which leads to the fungus being unable to maintain its structure and ultimately dying. It’s a bit like taking the bricks out of a wall, eventually, the wall will collapse.

The Antifungal Motorway

Azole antifungal medications are like specialised lorries on our body’s motorway. They have an important job: to target the fungi that can cause infections. While these drugs can be very effective, they also have the potential to affect other ‘vehicles’ on the road and interact with other medications you may be taking. Here’s why:

As mentioned earlier, your body has a special system for processing medications; in this system, a group of enzymes, known as Cytochrome P450 (CYP450), plays a significant role. One of the most important enzymes within this group is CYP3A4.

Think of CYP3A4 as a dedicated lane on the motorway, responsible for breaking down and clearing away many different types of drugs. When you take a medication, it enters this ‘lane’ and is metabolised at a certain speed, ensuring that the right amount of the drug is circulating in your body at any given time.

Here’s where azole antifungal medications come in. These drugs can be a bit like roadwork on this CYP3A4 motorway lane. They slow down the rate at which CYP3A4 can metabolise drugs. When azole antifungals are present, they cause a bit of a ‘traffic jam’, slowing down the metabolism of other medications that use the same CYP3A4 pathway.

What does this mean for you? Well, if you’re taking another medication that also relies on the CYP3A4 pathway – and many drugs do – this slowdown means that the other medication stays in your body for a longer time and at higher concentrations. This can effectively increase the strength, or potency, of that medication, which might lead to an increase in side effects or even potential toxicity.

The Importance of Communication

Understanding drug interactions can feel overwhelming, but don’t worry. Your GP, specialist or pharmacist can help you navigate this landscape, however, it’s crucial that you share all the information about any medications, supplements, or herbal remedies you’re taking with your Doctor. Even things that are purchased over the counter that may seem harmless can cause interactions.

If you are on azole antifungal medications and are concerned about interactions with other medications, you can check using our antifungal drug interaction website, http://antifungalinteractions.org/

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