Isoniazid has remarkable effects on killing dogs but has no toxicity to humans? Silly and naive

The fake rabies vaccine incident that happened in China recently exposes a basic fact of China that China is the country with the second largest incidence of rabies in the world following India. The chance of infection with relevant infectious diseases is low in developed countries due to their attention to disease prevention of domestic dogs and cats, and the small number of stray dogs and cats there reduces the risk of disease spread, while, due to limited economic levels and poor disease control, most developing countries have a large number of stray dogs and domestic dogs that are not under control, and the incidence of rabies there is high due to reasons like low vaccination rate, low consciousness of rabies prevention, and lack of animal shelters.

Interestingly, someone suggested on the internet to efficiently kill stray dogs by extensively spreading animal food packaged by isoniazid to each community and park, so as to force the Chinese to form the safety awareness for keeping dogs, which was highly regarded. And there has been the incident in Beijing that someone deliberately dispersed bait containing isoniazid in a large area in a community to eliminate unleashed pet dogs.

Isoniazid (CAS: 54-85-3)

In the online article, there are two reasons for highly recommending isoniazid: one, isoniazid is a good drug that is not toxic to humans, instead, it is very conductive to humans because it can treat diseases difficult to treat such as tuberculosis and is generally considered safe; two, isoniazid is highly toxic to dogs: administered according to 0.15g/kg, it will kill a dog in 90min, which requires an extremely low cost, while the artificial method to kill dogs such as chasing after and beating dogs with clubs is cruel and not acceptable to the society, which has low efficiency but high cost; three, using isoniazid can avoid the compliance with legal requirements and is considered in the article to not belong to spreading poison: spreading highly toxic substances such as tetramine to public places might kill children or  tramps, etc. due to eating by mistake and harm public health, being an explicit crime of spreading poison, but spreading pharmaceutical products is not included in such crime.

According to provision of the Criminal Law of China, whoever commits the crime of spreading poison that has not caused harmful consequences shall be sentenced to fixed-term imprisonment of not less than three years but not more than ten years; according to provision of Article 115 hereof, whoever commits the spread of poison to public places that causes serious injuries, death or heavy losses to public and private property shall be sentenced to fixed-term imprisonment of not less than ten years, life imprisonment, or death penalty, and if the damage is extremely serious, he shall be sentenced to death penalty or life sentence.

However, I have a question to the new research in the abovementioned article: what are the reasons for the high toxicity of isoniazid to dogs? The explanations on the internet are as follows: dogs have different genes from humans, and such drug cannot be metabolized in dogs, thus it kills them. Therefore, the large-area dispersing of isoniazid is not spread of poison, which is totally nonsense!

For example, 4 references in the 7 at the end of the article are about the pharmacokinetic study of isoniazid conducted on dogs, which means that isoniazid cannot directly kill dogs. Isoniazid could still be metabolized in dogs, and the dogs used for the experiment were still alive after completion of the metabolism. Most surprising, not only can isoniazid be used to treat the tuberculosis of humans, it can also be used to treat that of dogs and cats. Then, what killed the stray dogs? Apparently, it was the dose of isoniazid: the overdose of isoniazid would easily kill patients due to poisoning. The article mentions many times that the dose of 150 mg/kg of isoniazid produced the most ideal lethal effect on dogs that died in 30~90min after taking the drug, meaning that low dose will not be lethal.

Adverse reactions of isoniazid in treating the human tuberculosis include: unsteady walking or numbness and tingling, burning sensation or painful fingers (peripheral neuritis); dark urine, and yellowish eyes or skin (hepatotoxicity); poor appetite, abnormal fatigue or weakness, nausea, or vomiting (early symptoms of hepatotoxicity); blurred or declining vision, complicated with or not complicated with sore eyes, and convulsions (neuritis; neurotoxicity). The normal dose for humans to use isoniazid as drug therapy is 15mg/kg, and the lethal dose of the drug to humans is 200mg/kg, with a difference of only over 10 times, therefore, isoniazid can be called a toxic drug with a very small safety range. And its dose to kill dogs is very close to the lethal dose to humans (0.15 g/kg vs. 0.2 g/kg). After isoniazid poisoning, liver and kidney will have internal damage and internal hemorrhage, and cause neurotoxicity, to eventually kill the body.

To sum up, isoniazid has strong toxicity in clinical application, however, it is still a clinical first-line anti-tuberculosis drug because there is no drug that can substitute it. There are frequent poisoning and death incidents of overdose or suicide with isoniazid, therefore, it is too silly and naïve to say that isoniazid is safe and not toxic to humans; instead, it is a highly dangerous toxic substance, despite its ability to treat diseases at a low dose. And the spread of it in a large dose may violate the Criminal Law and lead to the calamity of imprisonment.

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