Bingor Says: Buffetting : Animal Handling 101- Panadol and animals

Disclaimer: This is an article written by a veterinary student. All information is based on non-professional interpretation of the student and is not subjected to any responsibilities of the readers' disposal.

I'm pretty sure I would have made a great pharmacist with my flair for pharmacology. Heck, we literally became dispensers of drugs over 1 semester of studies only compared to the professional pharmacy students. Yet, we only prescribe and dispense; we can't compound(aka make) drugs.

The MYTH BUSTING
Paracetamol, also known as acetaminophen is the generic name of a non-steroidal anti-inflammatory drug(NSAID) named after its chemical name of N-acetyl-p-aminophenol is an easily retrieved over-the-counter drug commonly used in any household. Widely known as Panadol in Malaysia, the antipyretic drug is usually used to relief headache and fever in most cases.

With its miraculous use, it is normal for us to actually consider its use even for animals. If it works well in human, of course animals would be fine right?

This is when you are WRONG.

Drugs consumed in our body requires several organic mechanics for them to release the active ingredient and work on our body's biochemical pathways. In this case, acetaminophen serves the same as well.

However, species variation does prevail in every single drug used, zoonotically or interspecies.

While human can take up to 4000mg for an adult in a day without any adverse effect(recommended dose of 1000mg), cats only can withstand up to 100mg/kg while dogs 600mg/kg.

That means, one tablet of conventional acetaminophen of 500mg can already kill a cat weighing 2.5 to 3.0kg; while a 5 kg cat is already considered overweight.

In fact, acetaminophen is never prescribed for veterinary use; regardless of their species.

WHY? The mechanism

The metabolic pathway of acetaminophen in the liver includes 3 different pathways; the glucouronidase, the sulfonation as well as the cytochrome p450 pathway.

In cats, the first 2 mechanisms are extremely limited due the lack of required enzymes; hence a high dependence on the latter pathway. However, a high dose of acetaminophen renders the ability of the pathway to metabolize the incoming drug concentration; leading to a problem of Acetaminophen Toxicosis.

In the cytochrome P-450 pathway, acetaminophen is metabolized into NAPQI, a toxic substance; which requires the conjugation with gluthathione from the body reserve to be metabolized into cysteine and mercapturic acid which are non-toxic. The depletion of the gluthathione reserves in the cat's body due to a high acetaminophen dosage will lead to a high accumulation of toxic NAPQI in the body.

Gluthathione depletion leads to red blood cell oxidation injury while methemoglobin, an alternative form of red blood cell will be produced due to the oxidation of Fe2+ haem group to Fe3+ haem group. Red Blood Cell oxidation causes the death of the RBC leading to jaundice; while the failure of methemoglobin to bind to oxygen due to the inability of Fe3+ to be further oxidized causes a cyanosis effect(pale from hypoxia). NAPQI accumulation also damages the liver, contributing to the occurrence of jaundice.

The Signs
Once you have accidentally fed your cat or dog with panadol, there are signs that you can have a look out for:
1- Cyanosis- pale and blue appearance
2- Jaundice- yellow staining on the eyes and gums
3- Pallor- pale and blue and no energy
4- Facial edema- swelling of the face for which the bouncing back of skin after pressure is more than 2 secs.
5- Hypersalivation

courtesy of catvando

The Right Thing to do:
Send your cat or dog to the vet immediately. The vet will be able to diagnosis and assess what treatment to be given to the cat. In most cases. the vets will try their best to accomplish the goals below:

1- Prevent further absorption of the drug in the animal; usually emetics to induce vomiting or a gastric lavage if your animal is already comatose. An activated charcoal may also be prescribed. These procedures are only useful when the toxicosis is recent and the drug is consumed within few hours.

2- Antidote prescription; in this case a mucolytic named acetylcysteine. The drug works was a gluthathione precursor to supply the body with enough gluthathione for the conjugation of NAPQI into a non-toxic product. This drug is the first line drug to be considered in every acetaminophen toxicosis as it is the antidote to the problem source.

3- Reduce methemoglobin presence in the body to replenish the normal RBC . Vitamin C will be prescribed along with a single dose of methylene blue.

4- Supportive treatment if the cat or dog is extremely ill; usually with blood transfusion, IV drip and oxygen provision. Cimetidine, a histamine-2 agonist may also be prescribed to inhibit the action of cytochrome P450 in generating more NAPQI toxic.

The Summary:
Responsible pet ownership does not stop at providing food and shelter and love to the animal. It includes understanding the general physiology of the animal as well as dos and don'ts in making sure the veterinary health of the animal is up to par. Never anthromorphize animals.