Swollen Feet/Legs as a Drug Side Effect

Factual Questions
1

The situation involves someone taking some drugs which have listed, on the paper that comes with the prescription, a multitude of possible side effects, including swollen feet and/or legs. Someone begins taking this drug and begins having this side effect. So he calls his doctor - a very respectable fellow, with awards and studies published in respectable journals etc. - who expresses skepticism as to whether swollen feet are in fact a side effect of this drug (he suspects a protein imbalance or something like that) and is in general not concerned.

The specific questions are:

Why might a drug have this particular side effect?
What is the worst case scenario in the case of someone just ignoring the issue, in terms of long term effects or possible violent flare ups?

2

Call his nurse, who may be more up to speed on the drug, or your pharmacist.

From WebMD:

3

Thanks, but this cite refers to naturally occurring swelling. I’m wondering about drug side effects. (Is the side effect necessarily an artificially induced version of these other forms of swelling, or could it be some completely different phenomenon?)

Interestingly, I looked at some respectable drug websites and they do not mention swollen feet as a side effect of this particular drug. Who knows.

4

Drugs can cause swelling (edema) by a number of possible routes such as:

  • salt retention (from drugs like prednsione, NSAID’s eg, naprosyn, motrin)
  • changed “tone” of the blood vessels (eg. verapamil and other calcium blockers)
  • allergy (almost any drug)

Some drugs cause swelling as part of a bigger picture of problems (such as kidney failure or heart failure)

So, without knowing which drug you’re talking about, it’s difficult to say more.

Personally, I’d worry about swelling in somebody taking certain diabetes medicines and NSAID’s.

5

Thank you. The drug in question is Purenithol (used for any number of conditions, including auto-immune malfunctions). I don’t see anything about swelling here. OTOH, it is listed here.

The question would be what process would causing such a reaction from this drug, and what is the worst case scenario if it is ignored.

6

Well, it must be pretty rare.

I can find no reference to edema as a side effect of mercaptopurine in my sources. A preliminary search on PubMed seems uninformative too.

To answer your question, I cannot think of a (patho)physiologic reason to account for the development of edema secondary to mercaptopurine use.

7

Izzy this is gettingt close to playing doctor, but what is the indication for purinethol?

8

A quick micromedex search turned up a serum sickness-like reaction, hepatotoxicity, and anemia as know toxicities of MP that potentially account for edema. All three would likely have other (more prominent) symptoms.

9

I’m not trying to be difficult, but how would you relate the development of edema to hepatotoxicity or anemia? Sure, you can invoke cirrhosis and high output heart failure respectively, but surely such consequences wouldn’t be listed under the heading of edema. They’d be called what they are. Otherwise, why not list every conceivable consequence of hepatotoxicity and anemia as unique possible side effects.

10

You are correct regarding my reasoning. I wonder why you find fault?

11

Thanks, guys!

Crohn’s Disease. (What is the difference?)

12

“Fault” is way too strong a word. I’d say “imprecise” is more what I’m thinking. What do I mean?

(I assume you’re a health care professional, so will use medical terminology)

When I see the term "hepatotoxicity with respect to a drug, I think of it as meaning either acute liver damage or a more insidious process leading to cirrhosis or fibrosis. In the former case, as might occur with almost any drug, the manifestations may be purely biochemical (eg. raised transaminases) or may be overt (jaundice, encephalopathy). Edema, if it even occurred in the acute setting, would be an irrelevant and nonspecific finding. Most importantly, I cannot conceive of edema being the sole manifestation of acute drug-induced hepatotoxicity.

In the latter, insidious-onset type of drug-induced liver damage, such as might occur with methotrexate, the manifestations are quite likely to be part of a constellation of signs (eg. variceal bleeding, encephalopathy, jaundice, ascites, etc.). Certainly there can be edema, but, once more, it is difficult for me to imagine a clinical scenario where the only manifestation of drug-induced cirrhosis is edema. So, to single out edema as a side effect of methotrexate, for example, is a real stretch and seems almost misleading.

Regarding anemia leading to edema, that would be even more of a stretch, or at least would require a number of intervening developments which would be expected to have their own, prominent, manifestations. It is true that a drug could cause anemia and that could lead to high output failure, and that heart failure leads to edema, ergo anemia can cause edema. But, again, a more straightforward way of listing the drug’s side effect in this regard would be to simply say “can cause anemia”. More importantly, if the anemia becomes severe enough to cause high output failure, I’d bet you’d know about it way before there was edema.

I should also add that anemia causing heart failure in an otherwise health person would be very rare.

I’ll close with an example. Let’s say a potential side effect of a drug is hyperglycemia (eg. prednisone, dilantin). I would certainly agree that listing polyuria and polydipsia is fair and helpful. However, listing retinopathy, or neuropathy, or any other diabetic complication, while theoretically true is misleading and imprecise more than anything else.

I 'm not sure that I’ve made myself as clear as I would have liked but hope you can see what I’m getting at.

13

[sub]pssst! choosybegger! You know you’re dialoguing with the head of the internal medicine department at a major teaching hospital, right? Publishes in JAMA and all that? You do? Good! Carry on.[/sub] :smiley:

14

Thanks for the heads up, Qad :wink:

KG, I generally agree with your analyses. I think I covered my ass though in my post.

***bolding added here

I approach answering questions here differently than in the clinic. The implausible (but possible) while possibly inappropriate for direct conversation with patients, IMHO, has a place here. In any case, a disclaimer came attached to my extended reasoning (see above).

I noted (as did you) that edema was not a primary side effect of MP. The three side effects I list may lead to anemia.

The thing is we know little (actually nothing) about the underlying health of the individual in question. Until Izzy’s last post, we didn’t even know the underlying illness. I considered the possibility that the patient in question was chronically ill, possibly with a borderline heart, liver, or kidneys. In this case (possibly) all they’d need is a little push to become floridly symptomatic.

I take slight issue with the example of the long-term effects of diabetes. I agree with it in principle (that far removed secondary effects deserve less attention than the primary effect) but the effects you mention typically don’t appear until at least 10 years after disease onset. Edema is a much more rapid consequence of heart and possibly liver failure.

Overall, I doubt we’re far apart in our views on this. My goal is to provide accurate opinions reflective of the current state of medical science. I speculate more here than in the office, but this is the SDMB.

It can make all the difference. Some diseases may predispose one to development of edema. The symptom sometime is a primary manifestation of the disease (drug is not at fault), sometimes is solely from the drug (disease is not at fault) and sometimes the drug and disease each have partial roles.

A good example is using calcium channel blocker to control high blood pressure in patient with an underlying predisposition to the development of edema (say someone with a history of left hip surgery). Without the drug, there’s no edema. In a person with a non instrumented hip, there’s no edema on an equivalent dosage. Combine the two, however and whammo, edema.

Bad Crohn’s may cause protein calorie malnutrition, leading to low serum albumin. This may contribute to edema. Sometimes it’s only a coincidence when a particular symptom appears on starting a drug. Not that this is the case here, but it needs to be considered.

15

These are excellent examples and I agree completely with the points that you’re making with them.
I guess the main issue I had with linking edema to mercaptopurine is that it may be (implicitly) misleading. If the edema is an epiphenomenon of a more fundamental complication (such as cirrhosis), it behooves whomever’s listing the side effects to include the more fundamental complication on the list. IzzyR: Is cirrhosis or anemia or heart failure on the list of potential side effects you were told about on the info sheet that came with the prescription?

choosybeggar: That nice Qadgop MD fellow exaggerates my abilities! I’m sure you’ve come to appreciate that it is QtM who is the impressive doc around here.

16

I wouldn’t think that’s an issue here. The Purinethol regimen was begun about a month after a ileocolonic resection, at a time of Crohn’s remission, and rapid regaining of lost weight. And the swelling began within a week or so of the first dose of the drug (with no other symptoms). Combine that with the warning on the insert, and it seems like it is a direct side effect.

I’m almost positive that they were not. (The sheet was more along the lines of practical things to look for, rather than warnings of long term effects.) Pretty close to (if not exactly the same as) the second link in my third post to this thread.