After they have served their purpose, drugs in the body are often broken down into other molecules, and then they are excreted. In acetaminophen's (Tylenol's active ingredient) case, animals get rid of a combination of unmetabolized acetaminophen and breakdown products.
In certain mammalian cells, acetaminophen is metabolized to its highly reactive metabolite N-acetyl-p-benzoquinoneimine(NAPQI). More specifically, tylenol is oxidized by cytochromes as it loses a pair of hydrogens and a pair of electrons. NADPQI can kill cells, but it is usually picked up by other molecules and gotten rid of before it does too much damage to the liver or before it modifies hemoglobin. In short, all goes well if there isn't too much NAPQI produced.
When a body gets rid of the acetaminophen, even before the reactive metabolites are made, it does so by using the enzyme glucuronyl transferase which conjugates acetaminophen to glucuronic acid for excretion.This brings us to the three reasons why cats can't tolerate tylenol.
(1) One problem with cats is that compared to dogs, rats and humans, they have very little of one type of glucuronyl transferase that happens to be very specific for acetaminophen. So instead of leaving their body, tylenol sticks around and gets converted into an excessive amount of reactive NAPQI.
Excess NAPQI alters hemoglobin. How? Having had lost electrons in an energy-requiring reaction, it now has the potential to get them back, and it does so by removing an electron from hemoglobin's Fe+2 to create Fe+3, converting it into methemoglobin.
(2) Cats have very little of the enzyme that's needed to convert Fe3+ back to Fe2+, so they get stuck with higher levels of methemoglobin. One problem is that this substance does not do an effective job delivering oxygen to tissues.But it gets worse.(3)Compared to most mammals, cats have two to four times more reactive sulfhydryl groups in their hemoglobin, making it more prone to oxidation. After the formation of Fe3+, the oxygen-transporting molecules eventually break down, solidifiy and cling to the surface of red blood cells. These so-called Heinz bodies make oxygen-carrying cells fragile, and the spleen's macrophages eliminates them. The cats quickly become anemic and weak. All this happens in just a few hours.
According to the Merck Veterianry Manual, the toxic dose for tylenol in a cat is 10 to 40 mg/kg , and even the lower end has proved fatal for some kittens. In contrast the LD50 for rats is 360 mg/kg.
Treatment for tylenol-poisoned cats includes fluids and blood transfusions, and the reducing agent ascorbic acid (vitamin C) which counters the oxidative tendencies of NAPQI.
Incidentally while digging into the literature to write this article, I came across a likely mechanism for tylenol's pain-killing properties. Two forms of THC, the psychoactive drug in marijuana, bind cannabinoid receptors in the brain. It happens because one of the tail projections of the THC molecule "impersonates" anandamide, which is produced naturally in the body. It turns out that in the brain and spinal cord tylenol, following a deacetylation reaction, binds to another chemical and forms a cannabinoid(THC-like molecule). Through an ensuing mechanism that blocks reuptake, it also elevates levels of anandamide in the brain
References:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC340185/
http://www.addl.purdue.edu/newsletters/1998/spring/acet.shtml
doi.wiley.com/10.1002/jps.2600630906
http://www.ansci.cornell.edu/plants/toxcat/toxcat.html
http://emedicine.medscape.com/article/820200-overview#aw2aab6b2b2
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/214009.htm
The other day, I came across a toadstool poison that contains a hydrazyl moiety, but I’ve forgotten where the link is, otherwise I would like to show it to you.