• 28 Nov 2017
  • 11 min
  • 28 Nov 2017
  • 11 min

Dhineli Perera interviews clinical pharmacologist Darren Roberts about how a patient’s regular medicines can cause adverse effects during intercurrent illness. He gives advice about diuretics, antihypertensives, diabetes medicines, corticosteroids and digoxin. Read the full article in Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

I'm Dhineli Perera, your host for this episode, and it's a pleasure to be speaking to Darren Roberts today about medication management on sick days. Darren writes about the management of medicines and patients with intercurrent illness in the October edition of Australia Prescriber. Darren, welcome to the program.

Thanks Dhineli, great to be here.

So Darren can you start by telling us why patients could be at increased risk of adverse effects from medicines when they are unwell?

Dhineli there's multiple reasons why patients may be at increased risk. It could relate first of all to comorbidities. It can also relate to the medications that they take so, depending on the combination of those two factors, you can almost make a perfect storm. This could lead to exacerbation of the illness and even other injuries which wouldn't be anticipated. I guess the illnesses that are of particular concern would relate to those which cause hypotension, those that are associated with a decrease in their volume status, so if you’ve got severe vomiting, diarrhoea and any other organ injury.

And so what are the pharmacokinetic factors of interest when managing medicines on sick days?

Any pharmacokinetic parameter can be disturbed in someone who is on a sick day and the likelihood, this depends on severity of the illness. The two key ones though that we think about relate to absorption and elimination. So for example if you've got severe gastroenteritis with vomiting and diarrhoea, tablets may not be absorbed at all and so a whole range of medical conditions can be exacerbated be that related to pain or Parkinson's disease. If you've got an acute illness that causes a decrease in clearance, for example acute kidney injury is one of the most common reasons for this, then there is a risk of accumulation of that drug and then this can cause toxicity, making things worse, and it's in these patients that we really need to think about an adjustment of their usual dose.

So are there any other comorbidities that need to be kept in mind?

The big three that we always think about are chronic conditions, so it relates to patients with chronic kidney disease. They've got impaired homeostatic responses. Heart failure for the same reasons also, and also patients with diabetes. But as we all know there's varying spectrums of severity of these different conditions and not everyone with one of these diagnoses will be at risk. There's also acute medical conditions that we also need to think about and the key one for that is acute kidney injury, and this is generally patients who are sick enough to go into hospital where the kidneys are sufficiently impaired, for example due to dehydration or hypotension. These are conditions that in particular would make someone at risk of adverse events.

When and why are there some medication formulations that need to be considered for adjustment?

It's primarily the slow-release formulations. These medicines are designed to release the drug when you've got a normal gut transit time, so anything that's causing this to be changed, for example severe diarrhoea, all mean that there is less opportunity for the drug to be absorbed and then the bioavailability goes down and then you get suboptimal blood concentrations. As mentioned beforehand this may cause problems with withdrawal, discomfort or immobility, depending on what the problem is.

And so can you talk us through what you consider are the key points for managing antihypertensives and diuretics on sick days? I think you touched on volume depletion and the importance of considering that.

Yeah for sure. There's a very large number of diuretics, very large number of antihypertensives, not all of them are a problem. In general it depends on the severity of that person's illness. If they're coming to hospital then there's more opportunity of which to monitor them closely. If you've got volume depletion then diuretics are just going to make that worse and increase the risk of acute kidney injury and electrolyte dysfunction. So any diuretic I think can be withheld at least for a couple of days until the acute illness is resolved. The antihypertensives is a bit more of a tricky one because a lot of antihypertensives have a long half-life so they can have effects that persist, and also in some of the antihypertensives, if you stop them abruptly you can be at risk of a withdrawal syndrome whereby you can get hypertension tachycardia afterwards, and the two drugs that we are particularly concerned about there in terms of the withdrawal or rebound if they're stopped are clonidine and perhaps beta blockers. And so in those cases we may dose reduce and just sort of see how they go. But there are some blood pressure medicines which, certainly in my opinion, should be stopped on people who have a significant sick day, and that’s the angiotensin II receptor blockers, the sartans and the ACE inhibitors. These just compound problems in the kidney, the people who are hypovolaemic and hypotensive where the normal counter-regulatory processes are impaired, and this is made worse by these medications and it just increases the risk of exacerbating the acute kidney injury.

Darren, on that same topic, if they're on a big dose of, say, an ACE inhibitor and we do stop it when they're sick, can we go straight back onto the dose that they were on before or should it be titrated back up again?

Again this depends on the severity of the illness. Most patients who are well enough to remain in the community at home, they can go straight back on their usual dose.

So, similarly, what would the key points be for diabetes medicines?

Actually diabetes is, ah, we’ve got some great guidelines to provide advice to both prescribers and also patients in terms of what to do. Certainly anyone who's acutely unwell, particularly if you've got vomiting and diarrhoea and at risk of hypotension and volume depletion, should cease metformin until they start to improve. That's very important because metformin can accumulate and cause toxicity and has been associated with deaths. In terms of the other medications, we need to ensure two things. One is our patients know how to measure their own blood glucose concentration, and number two is that they need to increase the frequency of this. So for example with type 1 diabetes patients should check their blood sugars every two to four hours and, in the event that there is an increase in the blood sugars, then we need to give supplemental doses of the insulin. Doses vary so much between the different patients. If a patient requires more than two extra doses, that's when it suggests that they should be seeing their doctor, just to make sure they can get some further guidance and monitoring. Type 2 diabetes is a bit easier. You don't need to monitor it as frequently, it's suggested that you should monitor it four times a day during a significant illness and, if the level is more than 15, then you can increase one of the regular doses. For example if the morning dose of insulin could be increased by about 10 or 15%, and this will allow for the blood sugar to come down. There's a few other medicines as well which are important of course for diabetes. There's the sulfonylureas. These can cause a decrease in blood glucose and so if you've got anorexia, which is not uncommon with a lot of infections and decreased intake, then sulfonylureas may actually risk getting a hypoglycaemia. Similarly there's the SGLT2 inhibitors, the flozins. Actually a part of the way they operate is that they are diuretic as well, and so these would also be medicines which could compound hypovolaemia in acute illness. We don't have a lot of data about those drugs because they’re relatively new, but certainly I don't think there would be anything lost by withholding an STGL2 inhibitor and a sulfonylurea during acute illness and then regularly monitoring the blood glucose.

I guess the key point to remember there would be that a low sugar is far more dangerous than a higher one, so I guess as long as our patients are aware of that. So what about managing corticosteroids on sick days? Do the same rules apply for short-term versus long-term use of these medicines?

There's a bit of debate as to when the duration of steroids becomes significant, that if you've had prolonged corticosteroids they'll be blunting at the hypothalamic-pituitary-adrenal axis and so then with the acute illness then there may be an impaired physiological response to that. There're differing opinions on this. Generally we think more than 5 mg a day for about two weeks may be sufficient to cause an impaired physiological response.

And so moving on to digoxin. Now this can be another tricky medicine to manage with such broad interpatient variability. What would be your advice in managing its use on sick days?

Digoxin has actually two main areas of concern in the acute illness. First of all, if you've got vomiting and diarrhoea, it can cause hypokalaemia and we know that increases the toxicity of digoxin. It sensitises its effect on the heart so you're more like to get dysrhythmias. The other factor that happens as I mentioned before is you get acute kidney injury and that causes impaired clearance and then you get accumulation. Digoxin has also a fairly long half-life. Even with therapeutic dosing it generally exceeds about 24 hours, so my perspective is, first of all, the way we use digoxin now differs to the way we used to in the past. We generally use lower doses aiming for a lower concentration so we do have some degree of buffer. It's being used to augment other existing treatments so from my perspective, if someone has an acute illness, they can very comfortably withhold their digoxin for a couple of days and then restart once that's resolved.

Okay, so I guess the take-home message for all of us as health professionals is to make sure that our patients are aware that there are options to help make sure that they are safe when they're taking medicines around times of intercurrent illness.

Definitely, I think we need to empower patients both in terms of education about the risks of taking these tablets but also to let them know that a lot of these medicines, the benefit that we see from these medicines is actually taking them over a prolonged period of time. We're talking months or years. This is where the data has come from saying these medicines are useful. Little is lost by missing them over a couple of days, in particular there can be more harm from continuing to take them. We need to know specifically what conditions we're talking about and they're the ones I've already mentioned in terms of volume loss and if they've got hypotension and that they should then restart them only after maybe two or three days, and if the illness is persisting beyond that, then I think that's where medical review is required.

Excellent. Well that's unfortunately all the time we've got for this episode. Thanks for joining us today Darren.

Thanks Dhineli. My pleasure.


Darren's full article’s available online at nps.org.au/australian-prescriber and like our whole journal it's free. Subscribe to get the latest Australian Prescriber delivered straight to your email inbox and follow us on twitter @AustPrescriber to get the latest updates. The views of the hosts and guests on the podcast are their own and do not represent Australian Prescriber or NPS MedicineWise. I’m Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.