Health
August 15, 2005 / 7:48 PM / AP
Women taking daily amounts of non-aspirin painkillers — such as an extra-strength Tylenol — are more likely to develop high blood pressure than those who don't, a new study suggests.
While many popular over-the-counter painkillers have been linked before to high blood pressure, acetaminophen, sold as Tylenol, has generally been considered relatively free of such risk.
It is the only one that is not a non-steroidal anti-inflammatory drug or NSAID, a class of medications the federal government just required to carry stricter warning labels because of the risk for heart-related problems. Those include ibuprofen (sold as Advil and Motrin) and naproxen (sold as Aleve). Many had turned to those painkillers in the wake of problems with prescription drugs, such as Vioxx.
However, the new study found that women taking Tylenol were about twice as likely to develop blood pressure problems. Risk also rose for women taking NSAIDS other than aspirin.
"If you're taking these over-the-counter medications at high dosages on a regular basis, make sure that you report it to your doctor and you're checking your blood pressure," said Dr. Christie Ballantyne, a cardiologist at the Methodist DeBakey Heart Center in Houston who had no role in the study.
The research found that aspirin still remains the safest medicine for pain relief. It has long been known to reduce the risk of cardiovascular problems and was not included in the government's requirement for stricter labels for NSAIDs.
The study involved 5,123 women participating in the Nurses Health Study at Harvard Medical School and Brigham and Women's Hospital in Boston. None had had high blood pressure when it began.
Results were published online Monday in the American Heart Association journal Hypertension.
"It certainly sets the basis for more studies," said Dr. Stephanie Lawhorn, a cardiologist at St. Luke's Mid America Heart Institute in Kansas City. "Most of the time we think that things like acetaminophen are fairly safe drugs."
In this study, the risk of developing high blood pressure for women who weren't taking painkillers was about 1 to 3 percent a year, researchers said. They found that that women ages 51-77 who took an average daily dose of more than 500 milligrams of acetaminophen — one extra-strength Tylenol — had about double the risk of developing high blood pressure within about three years.
Women in that age range who take more than 400 mg a day of NSAIDS — equal to say two ibuprofen — had a 78 percent increased risk of developing high blood pressure over those who didn't take the drug.
Among women 34-53 who take an average of more than 500 mg of acetaminophen a day had a two-fold higher risk of developing high blood pressure. And those who took more than 400 mg of NSAIDS a day had a 60 percent risk increase over those who didn't take the pills.
"We are by no means suggesting that women with chronic pain conditions not receive treatment for their pain," lead author Dr. John Phillip Forman, of Harvard Medical School and associate physician at Brigham and Women's Hospital in Boston, said in an e-mail. "By pointing out risks associated with these drugs, more informed choices can be made by women and their clinicians."
Previous research linking these drugs to blood pressure problems did not look at dose.
The results in this study held up even when researchers excluded women who were taking pills for headaches, something that could itself be a result of very high blood pressure, said Dr. Gary Curhan, another study author also of Harvard Medical School.
As for why aspirin didn't raise risk, it might be because "aspirin has a different effect on blood vessels than NSAIDS and acetaminophen have," said Dr. Daniel Jones, dean of the school of medicine at University of Mississippi Medical Center in Jackson.
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