The chemistry between us
Caffeine as a gateway drug, part six
If you’re new to Lessons on Drugs, welcome! This is part six of the Caffeine as a gateway drug series where we explore how drugs work by examining the world’s drug of choice - coffee.
The challenge I’ve set myself is to try explain things in enough detail without requiring people to have a heap of pre-existing knowledge of how the body works, and to use as plain language as possible without ‘dumbing things down’ and being condescending. One of the things I’ve discovered along this journey is that it’s really bloody hard to do that, but I’m trying!
So far, we’ve looked at how drugs get into the body, move to the site of action, exert an action by interacting with a receptor, and get cleared by the body by metabolism in the liver.
Here are all the links in order if you want to go back to check out any earlier posts:
The focus for this week comes courtesy of a reader’s comment on an earlier post:
I’m now curious as to the difference in swallowing pills with water or coffee. I convince myself swallowing with coffee will speed up the process. I look forward to finding out.
- Debbie (all round wonderful human and supporter of Lessons on Drugs)
Things that go ‘fizz’
I wouldn’t say I was fully into science as a kid. But I was into making a mess, self initiated art projects and mixing potions out of random things I found in the garden. So, I’m quite sure if I had access to YouTube and all the cool kids science shows that are around now, I would’ve fully embraced the home experiments. I’m not sure I would have have sought out the recommended parental supervision though.
My husband may tell you that even now, where I am the parent providing said supervision, there are many examples of me pursuing kids science experiments at home where I haven’t fully thought out the consequences (aka mess) that would be created by them.
What can I say, I love making things fizz and gloop and all that sort of stuff.
The science at the heart of most of these home science experiments is some basic chemistry.
Want to make colour changing liquid? Put some pomegranate juice (or red cabbage liquid if you want to put in more effort and don’t have a pomegranate bush) into three different containers and add lemon juice (acidic pH), water (neutral), and dishwashing liquid (alkaline pH) and look for the difference.
Want to make a fizzy volcano? Add vinegar (an acid) to bicarb soda (a base) with some red food colouring to make bubbling lava (a mixture of a salt, water, and carbon dioxide).
Want make an egg bounce? Sit the eggshell (calcium carbonate) in some vinegar (an acid) and watch it slowly eat away at the shell (basically the same acid-base reaction as above).
Want to see something gross? Mix some coca-cola with milk and watch it separate and congeal (precipitation of calcium).
Why am I telling you this? Well these are the types of chemical reactions we need to keep in mind when we think about whether it’s ok to take coffee with medicines.
In part five we talked about drug-drug interactions that involve the liver enzymes working faster (induction) or being slowed down (inhibition). In this post we’re going to talk about the types of drug-drug interactions that are important to think about for drugs taken orally. To get us started we need to go back to where these drugs end up after you swallow them- your stomach.
A day in the life
Woke up, fell out of bed
Dragged a comb across my head
Found my way downstairs and had a cup
And looking around I noticed I was late
- A day in the life, The Beatles
But wait a second Paul, you haven’t taken your medicines yet!
Ok, let’s work through the options here and what it means for the environment within the stomach Paul’s medicines are going to find themselves in.
Paul’s had a good sleep. When he wakes up his stomach is empty and very acidic. If he takes his medicine like he’s instructed, with a full glass of water, this is going to dilute the stomach contents so they’ll be slightly less acidic. The water will also help the medicine to get into solution, which as we know from earlier posts is an important step for a solid form like a tablet or capsule. Because there are no other stomach contents to get in the way, the drug will move into the small intestine and absorb into the bloodstream pretty fast, within around 45 minutes to an hour.
Now Paul’s English and it’s the 1960s, so I’m going to assume that he doesn’t have a pot of coffee there ready to go as soon as he wakes and rushes to get ready in the morning. But if he were to swallow his medicine with just a small sip of water, a cup of coffee or juice (both weak acids) the contents of the stomach would be more acidic than if he had that full glass of water. If you don’t believe me, do the acid base indicator experiment with red cabbage and you’ll see.
For many drugs, sitting around in an acidic environment isn’t a problem. There are some drugs though, like penicillin for tonsillitis, that interact with acids. This means they can breakdown in the gut before they get absorbed into the bloodstream. The lesson here is, if you take a medicine that says “take on an empty stomach” on the label, you should take it at least one hour before food or two hours after food, and with a full glass of water.
Imagine that Paul is actually running late to meet his pals John, Ringo and George at the greasy spoon for a big fry up. This is before he turned vegetarian, so he gets himself a full English breakfast. Eggs, bacon, sausage, beans and toast topped with HP sauce, maybe some tomatoes too.
If Paul takes his medicine now, it’s going into a full stomach. This stomach has some work to do. Not only does it have to break down Paul’s medicine into solution, it also needs to break down all the solid food into their respective nutrients. These stomach contents had better like one another, because they’re going to be mixing around together in there for a while. There’s a party in his stomach and it’s just getting started.
The thing is, some drug molecules are a bit needy and don’t like being alone. They interact with the first decent molecule they find, form a bond and never leave them alone. In chemistry terms this would be called chelation or adsorption, something that indicates the drug has formed a complex with something else and can no longer be absorbed. This is another reason why some drugs are recommended to be taken on an empty stomach, like thyroxine.
The types of needy chemicals that like to form these complexes are things like ionised metals- calcium, aluminium, magnesium, zinc, iron, stuff like that. These are minerals that can be present in the food you eat, or you might take them as supplements or perhaps as an antacid to manage the reflux you’re about to get if you’re also going to sit down to an enormous breakfast like Paul. If a prescribed medicines is prone to having these types of drug-drug interactions, it should be written on the label to take on an empty stomach, or it may even have a little sticker on it telling you to avoid dairy, antacids or mineral supplements.
Now, if you’re taking one of these minerals as a dietary supplement, you might be wondering if taking them on a full stomach is going to impact on their absorption. Well, theoretically it might, but the reality is that if you don’t take them with food then you’re probably going to have a crook stomach. I don’t know about you, but if something I take gives me a stomach ache, I tend not to take it anymore. And you definitely don’t absorb any drug if you don’t actually take it! So my opinion is, it’s fine to take mineral supplements with food because if you have a true deficit you can always adjust your dose to get the level you need (based on medical advice of course).
Back to the party that’s happening in Paul’s stomach with everything mixing about.
The volume of food has a temporary buffering effect on the acid levels of the stomach just like the glass of water did, but it also triggers the stomach to get the gastric juices flowing. This means within about 30mins or so things are getting down on the dance floor of the stomach…the pH that is. It’s getting back to being very acidic. And it stays in this strong acid state until you put some more food or drink in there to dilute or buffer the acid. As we talked about earlier, this is fine for most drugs but it can cause some to break down before they get absorbed, just like the home made volcano but without the flowing red lava. (If you ever have anything resembling flowing red lava coming out of your digestive system, please phone an ambulance immediately).
A small number of medicines thrive in the acidic conditions of the stomach. The best example is a drug called itraconazole which is absorbed better in acidic conditions and is sometimes even recommended to be taken with something acidic like Coca Cola. If this is the case with a prescription medicine, it will be written on the label.
Some medicines have special coatings on them or fancy matrix like formulations that slowly erode like the eggshell in the vinegar. This type of coating can help keep the inner contents protected from the acid environment, allowing them to release lower down in the small intestine. The reason for this could be to protect an acid sensitive drug from breaking down too quickly, or it could be to protect your stomach from the irritation caused by the drug, as is the case with aspirin. This is called an enteric coating - sometimes indicated on a label by EC.
Other medicines have a special coating or matrix that’s designed to erode slowly, releasing the drug gradually over a period of time. Some capsules have this too - they look like little pellets inside. This is called a modified release product - indicated by things like SR, XR, Oros, LA, CR, CD, MR…there are so many now.
The take home message about these special coatings and formulations is, if a prescribed medicine specifically says on the label to ‘swallow whole’ it’s not just the pharmacist being pedantic and wordy- it could mess up the way the drug releases and gets into the body if you crush it.
So what’s the deal with taking medicines with coffee?
I know it’s a cop out, but ‘it depends’.
If you’re taking a medicine that’s recommended to be taken on an empty stomach, has an enteric coating or is a modified release product then the best thing to do is stick with taking as recommended with a full glass of water.
Other than that, well coffee is unlikely to have much impact. The medicine and coffee will pretty soon be mixing around in the stomach together anyway. And if you’re taking drugs regularly every day, you get to what’s called a ‘steady state’ where the small variations relating to absorption aren’t going to make too much of a difference to overall blood levels. But that’s another fun pharmacokinetics topic we shall cover in a future post.
In the meantime, check the labels, ask your pharmacist or doctor if you’re unsure, and make sure the coffee doesn’t burn your tongue on the way down!
We’ve now touched on what we call pharmacokinetic and physicochemical drug-drug interactions. To round out the introductory material on drug interactions, next week we’re going to take a look at drug-person interactions, technically known as pharmacodynamic interactions. Personally, I think these ones are the most interesting, so I hope you join us for another read.
If you’ve got any general questions or topics you’d like me to cover, please let me know in the comments. As you can see by this post, I’m responsive to feedback. Plus, it’s nice to know what people find useful or interesting.
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For those who are interested…this is actually the song reference in the post title. It didn’t have the same fit as The Beatles one though.
OK so I'm guilty of taking tablets etc with just a sip of water. It'll be a full glass from now on.
Thanks Lauren :)