Why do animals have such different responses to medicines?
What makes a medicine safe and effective for one species but highly toxic for another? A cow is very different from a lapdog, bird or tortoise, explains veterinary pharmacologist Ronette Gehring. ‘Animal species have entirely different reactions to medicines. We want to find out why.’
Why do the same medicines have such varying effects on different species?
‘That has several reasons. A medicine is a chemical substance that is introduced into the body by means of an injection or a pill. In order to be effective, that chemical has to travel through the body to reach the area where it needs to do its work. For example, if you take an aspirin for a headache it needs to reach the brain. However, it won't stay there forever; the medication will be absorbed by the body and excreted. Animals have different gastrointestinal tracts, different physiques and body compositions, and different capacities to absorb and excrete foreign substances. For example, just try comparing a very fit horse with a small fat dog.
So is that why you're not supposed to give your dog paracetamol?
‘Dogs can handle it well if you give them the right dosage, but paracetamol is very toxic for cats. That's because paracetamol damages red blood cells in felines during the metabolic process. But it can also be highly toxic in humans if the dose is too high, causing serious liver damage.’
So are there any specific medicines for certain animal species, like medication that's only intended for cats, cows or elephants?
‘There's a lot of overlap in the medicines we use on both animals and humans. For example, we use antibiotics, antiparasitic drugs, painkillers and anti-inflammatory drugs on all animal species. But there are also conditions that are specific to particular animal species, such as stomach ulcers in dogs and horses, or asthma in horses and cats. We treat those with drugs that are similar to those used in humans, but often in a different form or dosage.’
So isn't it hard to predict how an animal will react to a medicine?
‘Some factors are predictable and are based on the animal's body weight and composition. For example, it's easy to predict that many types of medicine will be absorbed slowly and poorly by cattle if administered orally, because they have so many stomachs. You can't make those predictions so easily for other substances. For example, absorption might depend on the enzymes that species use to break down a substance.’
So do different mammals also have different enzymes?
‘They do, but we also treat birds, reptiles and even insects here at Veterinary Medicine. It's a really broad spectrum, which also depends on the environment in which the species have evolved. What sort of substances have they been accustomed and exposed to? Still, there are some general rules of thumb to rely on here: the smaller the animal, the faster its metabolism, for example. Herbivores, who mainly eat plants, are also more tolerant of external chemicals. Still, those are only general patterns and there are always exceptions in biology. You're bound to run into surprises.’
You're currently trying to map out this diversity with mathematical models. How does that work?
‘We're using mathematical models to map out our current knowledge on the body's response to substances. Those models can describe a system more accurately than you could ever do with words. They also allow you to make predictions and test hypotheses. It's a lot more effective than just trying out substances on different animal species. The good thing about COVID is that people now tend to appreciate the usefulness of models a lot more. Pharmacological models allow us to pool knowledge from literature, databases and in vitro models; as a result, we only need to conduct targeted animal studies to fill in the gaps. In the process, we're helping to reduce, refine and find alternatives for the use of laboratory animals in biomedical research.’
So what's the ultimate goal here?
‘On the one hand, vets are clinicians: they're always focused on practical questions. Can I safely use this product, which isn't registered for cats, on a cat? If so, how, and in what dosage? We're also struggling with some broader questions: why do different species have varying reactions to the same medicines? And what role do their environments play in that process? If we can manage to map that information out more accurately and gain a greater understanding of the general principles, we'll be able to make better predictions.’
Will that also lead to better healthcare for animals?
‘Absolutely. We're veterinarians: at the end of the day, we all want to use the veterinary medicines at our disposal more safely and effectively. For example, we want to use antibiotics effectively and discover new alternatives. That's an immediate, day-to-day goal that benefits the patient. On the other hand, we also want to gain a better understanding of animal physiology so that we can predict how different species will respond to a particular substance. We can use our knowledge of humans to treat animals more successfully, but we can also apply our knowledge of animals to improve human medicine. If you can do that, you've really integrated the two fields. That's what I call One Medicine.’