Team finds why acetaminophen causes blood pressure drop

Researchers may have found the reason behind one side effect of receiving intravenous acetaminophen, according to new research with rats.

The painkiller acetaminophen is commonly used for headaches and ingested orally. Hospitals, however, administer acetaminophen intravenously. In this way, doctors and nurses can help critically ill patients unable to swallow one or more pills.

Furthermore, the drug works much faster intravenously, and the method allows healthcare professionals to precisely control the doses and the timing of its effects.

However, the intravenous acetaminophen has a serious side effect: a temporary large drop in blood pressure.

“Previous studies suggest it is quite a sizable drop. We are, for example, talking about drops in the range of 25-30 mm Hg from a systolic pressure of 120, and we now believe that we know the mechanism underlying this dangerous side effect,” says Thomas Qvistgaard Jepps, an assistant professor in the biomedical sciences department at the University of Copenhagen.

The drop in blood pressure occurs in both common and critically ill patients, he says. In the critically ill, six out of 10 have experienced the side effect, one third of these to such an extent that they require medical intervention.

This research is rather timely, given the unprecedented COVID-19 crisis and dramatic increase in critically ill patients that may be receiving intravenous acetaminophen in the hospitals to help with pain and fever management.

Despite the statistics, intravenous acetaminophen is considered to be a relatively stable drug used increasingly in the healthcare system, even though many doctors and nurses are aware of the potential side effects.

On this background, Jepps and his team set out to find a cause for the steep drop in blood pressure. They have now succeeded through studies in rats.

“Paracetamol [acetaminophen) bypasses the liver when administered intravenously, therefore it is metabolized differently to when you ingest it orally,” says Jepps. “It still gets metabolized, but it happens elsewhere in the body, where the subsequent chemicals can cause an effect that wouldn’t normally happen, if the drug was taken orally.”

Jepps emphasizes that most people should not be afraid to take painkillers as usual, as long as you stay within the maximum recommended dose.

More precisely, it appears that the residual products of the painkiller affect some of the potassium channels, which, among other things, regulate how your blood vessels contract and relax, thereby controlling your blood pressure.

By using drugs that block these potassium channels, specifically, the research team subsequently succeeded in reducing the side effect of the large drop in blood pressure in the test rats.

“Because we have identified the mechanism of how the side effect occurs, we believe we are able to offer a potential pharmaceutical design for a new kind of co-therapy: A type of paracetamol infused with another drug that prevents the drop in blood pressure,” says Jepps.

“However, blockers of the potassium channels we have investigated are not yet approved for human consumption and need to be developed and tested properly. We wouldn’t want to replace one side effect with another.”

The research group will next investigate how they can adapt drugs that block the potassium channels for humans. They are also investigating alternatives for blocking the potassium channels, for example, by affecting the enzymes involved in metabolizing paracetamol outside the liver.

The study appears in Atherosclerosis, Thrombosis and Vascular Biology.

Additional researchers from the University of Copenhagen and the University of California, Irvine, contributed to the work. The research received funding from, among others, the Lundbeck Foundation and EU’s Horizon 2020 program.

Source: University of Copenhagen

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