Blue Collar Scientist

Hi everyone! My name is Karen, and I’m a veterinarian. I’ve joined this blog to provide a roughly once-weekly column on medicine and related topics. I’m writing under the byline Iatros Iatra Polygenos¹, which in ancient Greek means - as far as we can tell - something like Doctor of Many Species.

A few years ago, I treated a young dog for something - I can’t even remember what now, but I do remember it was a painful condition. While the animal was in the hospital, we gave him carprofen - known commercially as Rimadyl - as well as lots of love. When it was time for the puppy to go home, we sent some carprofen with him, along with the usual instructions about dose. It looked like the puppy was on track for a successful recovery.

Later that night, the unfortunate puppy’s owners decided that the animal was in pain, and that the carprofen wasn’t working. So, without telling me or anyone else at the clinic, they gave the puppy a “natural remedy” - willow bark. Within a couple hours, the puppy was dead.

What happened here?

The post-mortem showed that the poor puppy had extensive internal bleeding and kidney and liver damage. These results strongly suggested the dog died of an overdose of NSAIDs. Carprofen is an NSAID, so I was initially worried that I had made a mistake on the dosage and inadvertently killed the dog through my own error. But when I met with the dog’s owners and had a look at the prescription bottle, the dosage was right. And the owners insisted they had complied with instructions and given the proper dose. A count of the remaining pills showed they were right.

That’s when they mentioned the willow bark they’d given the dog, and it all became clear.

NSAIDs are a class of drugs that reduce pain, inflammation, and fever. They are quite safe, as long as you use an appropriate dosage. But when an overdose occurs, bad things can happen very quickly. If the overdose is minor, the effects can include nausea, vomiting, and ringing of the ears - fairly innocuous. But if the overdose is severe, you can end up with bleeding in the stomach and upper part of the small intestine, dangerously high fever, uncontrollable hyperventilation which leads to a dangerous rise in the pH of the blood, disruption of kidney function, and a loss of the body’s ability to regulate potassium, which leads to loss of muscle control, the stopping of the heart, and eventually death. You can also get cerebral edema - a buildup of fluid in and around the brain - coma, hallucinations, and other not very nice symptoms. It’s important to note that these are the side effects of an aspirin overdose, or a willow bark overdose - they’re both the same type of chemical.

Willow bark was probably the first NSAID. It was first mentioned in the historical record back in the days of Hippocrates. The bark would be mushed up into wine to make a tincture. This potion would cause severe gastrointestinal discomfort, but it would kill pain. The active ingredient in willow bark is salicin, which looks like this:

The molecule is actually very close to that of another NSAID, Aspirin. The resemblance might be more obvious if you mentally rotate the diagram below about 120 degrees clockwise:

Both of these compounds - salicin and aspirin - are metabolized in the body to salicylic acid. Salicylic acid is toxic if there is enough of it around, so if you simultaneously take a safe dosage of aspirin, and a safe dosage of the active ingredient of willow bark, you are going to get more salicylic acid production in the body than the people who wrote the dosage instructions ever intended you to have.

Carprofen is a bit more complex and looks considerably different from aspirin and salicin, but if you look carefully, you can see that one end of the molecule is pretty similar to aspirin:

And indeed, carprofen is also a salicylate drug, just like willow bark and aspirin.

The fascination with natural remedies is causing a lot of problems in people and animals alike. Those who take natural remedies do not always disclose this to their doctor, let alone consult them in advance. This leads to interactions and overdoses that can be fatal. Just because something is “natural” does not mean it is safe!

Another problem is that the FDA does not regulate the manufacturing of natural remedies. Commercially manufactured medication is strictly regulated. The information on a drug’s label - including the amount of active ingredient, and the purity of the preparation - has to be accurate. If it isn’t, it can be recalled, resulting in a sharp financial loss to the manufacturer. In extreme cases, people can go to jail. But with “natural remedies,” the amount of active ingredient is not required to match the manufacturer’s claims, nor are there standards for purity. Depending on the “remedy,” you might be ingesting nothing but fillers from this week’s bottle, and getting more than is safe from the next batch.

Back when I was treating that unfortunate puppy, a lot of resources discussed the hazards of willow bark in terms of potential overdose and interaction with other NSAIDs. Now, there is more research to draw on, and the new information suggests salicin is less toxic and has a smaller chance of leading to upset stomach than aspirin. And it looks like the effects of salicin last longer than aspirin. But there’s bad news - willow bark is not pure salicin; it is also full of tannins, which are toxic and can damage the gastrointestinal tract. White willow bark preparations are between 8% to 20% tannins, but if you are going to get enough salicin for pain relief, tannins are unsafe at around 10%. At most of the measured concentrations, tannins lead to toxicity before a therapeutic dosage of salicin can reached. Tannins can also cause liver and kidney damage, so when they are coupled with drugs that are metabolized by these organs, the result can be deadly.

Based on this new information, I’m no longer so confident that my patient the puppy died of an NSAID overdose, caused by the double-whammy of two different drugs. It could have been a result of kidney damage from tannin toxicity, which made the puppy unable to metabolize the carprofen. Either way, the lesson is clear - NSAIDs, whether natural or medical, need to be treated with respect.

Oh, and one parting thought. I shudder to think about anyone giving an NSAID to a cat. Cats aren’t able to metabolize most NSAIDs, and giving them one could easily kill them, or lead to kidney and liver damage - or at best, just make them extremely sick.

1. I’m aware Iatros is masculine - if a real Greek scholar can help out, I’m all ears. [↩]

The Capital Times reports:

An 11-year-old girl died after her parents prayed for healing rather than seek medical help for a treatable form of diabetes, police said Tuesday.

…

[Everest Metro Police Chief Dan] Vergin said an autopsy determined the girl died from diabetic ketoacidosis, an ailment that left her with too little insulin in her body, and she had probably been ill for about 30 days, suffering symptoms like nausea, vomiting, excessive thirst, loss of appetite and weakness.

The parents explained that the reason their child did not get better as a result of prayer is that they did not have sufficient faith.

The mother believes the girl could still be resurrected, the police chief said.

The parents told investigators their daughter last saw a doctor when she was 3 to get some shots, Vergin said. The girl had attended public school during the first semester but didn’t return for the second semester.

If you didn’t catch it up there, the girl was 11 years old when she died. She hasn’t seen a doctor since she was three. She went more than two-thirds of her lifetime without medical care.

The girl has three siblings, ranging in age from 13 to 16, the police chief said.

“They are still in the home,” he said. “There is no reason to remove them. There is no abuse or signs of abuse that we can see.”

Social service agencies and the social work profession will continue to have difficulty establishing credibility amongst common-sense people as long as they continue to consider this sort of thing normal. It should be viewed as a form of neglect that necessitates professional intervention.

Will the parents be charged? I don’t know, but I doubt it. A Wisconsin state law was helpfully posted in the story comments:

State statute 948.03(6): A person is not guilty of an offense under this section solely because he or she provides a child with treatment by spiritual means through prayer alone for healing in accordance with the religious method of healing … in lieu of medical or surgical treatment.

The comments predictably have a bunch of religious extremists defending the parents’ actions as an efficacious response to sickness, even though every controlled study ever done has shown that prayer is ineffective at curing or even helping someone who is sick. Personally, I think it is fine to pray for your child to be healed, as long as you also get them some competent medical help. A sane, fit parent does anything and everything they can to save the life of their child.

Sometimes the issue when not seeking out health care is lack of insurance or inability to pay for an expensive treatment. The parents operate a small business, operating a coffee shop in a suburb of Wausau, according to the story. Diabetic ketoacidosis is both easily, and fairly inexpensively, treated - at least if you don’t let the condition progress to an acute, dangerous form. People who get it and seek medical attention do not die of it. But it is still possible that the parents didn’t have the money for the treatment, right? It could be they were praying not because they thought that was the best thing to do, but because they had no alternative - right?

Wrong.

Wisconsin has a health insurance program for children called BadgerCare Plus. You can sign up for it here, and it provides comprehensive services to any child under 19, whether they already have insurance or not. Services do require a co-pay. The co-pay ranges from fifty cents to three dollars.

I’m thinking that someone selling lattes for a living can afford a fifty-cent co-pay if it means saving the life of their child.

Several people sent this to me, but I saw it on Pharyngula first.