Does painkiller stop the pain?

Ibuprofen, during the COVID-19 pandemic, has become a fever-reducing analgesic for many.

It is generally used to reduce fever and relieve pain caused by a variety of conditions, such as headaches, toothaches, dysmenorrhea, muscle aches or arthritis.

But its effect is likely to “vary from person to person”. A 2020 article published in Scientific Reports looked at the effects of ibuprofen on the liver of mice and found that ibuprofen affected males and females differently.

Not only that, some existing studies have shown that the drug has a stronger analgesic effect on men than women. According to a study in the journal Brian, dorsal root ganglion neurons that produce persistent pain are different between men and women.

However, many painkillers are only created on the basis of clinical trials in male animals, which may explain why some painkillers are less effective against persistent pain in women.

There may be gender differences in the course and effect of medication

Physiological differences in pain are just one of many differences between men and women. At present, there are many cases showing that men and women may differ in the pharmacokinetic and pharmacodynamic characteristics of specific drugs. For example, women who ingest the same amount of the psychoactive drug diazepam have a larger distribution volume of the drug in their bodies. Clozapine, also a psychoactive drug, binds to plasma proteins at a significantly higher rate in women than in men. Not only that, but aspirin, as we know it, is cleared from women’s bodies at a much higher rate than men’s.

And, for some medications, women are at much higher risk of experiencing adverse effects.

A 2001 report by the U.S. Government Accountability Office found that 80 percent of drugs removed from the market between 1997 and 2000 posed greater health risks to women. For example, the antihistamine terphenadine (Seldane) and the gastrointestinal drug Propulsid are both more likely to cause potentially fatal heart arrhythmias in women than men.

Some cardiovascular drugs may also have gender differences, the European Society of Cardiology (ESC) Pharmacology and Drug Therapy Working Group published a position paper on gender differences in cardiovascular drugs in 2015, mentioned that some cardiovascular drugs have gender differences in the impact of adverse events, women are more likely to have serious adverse events. For example, women using diuretics and other cardiovascular drugs are more likely to develop drug-induced tip torsion ventricular tachycardia and skin diseases. And bleeding complications are more common in women.

However, despite the differences in drug pharmacokinetics between men and women, there are currently no sex-specific dosing recommendations for most drugs. We climbed on the platform of Syringa Medicine Assistant to retrieve 13 drug instructions that mentioned gender differences between men and women in the study, a total of 1,188. None of the instructions made recommendations based on gender.

In this regard, Tang Zhijia, a young associate researcher at the School of Pharmacy, Fudan University, explained, “Women are more sensitive to some adverse drug reactions. But the problem is that if the dose is reduced, the efficacy will not be achieved, although the adverse effects will be reduced. We usually look at the drug’s efficacy as the main indicator, after all, medicine has to be effective.”

“The influence of sex on drug selection should be considered more often than the influence of sex on drug dosage.” Tang Zhijia said that in their current clinical studies, it was found that SGLT-2 inhibitors, which are now more popular hypoglycemic drugs, have urinary tract infections in some women after use.

“The reason for this is related to female biology, because women have a shorter urethra and are inherently more prone to urinary tract infections than men.” Tang Zhijia said.

So can gender differences be taken into account when developing drugs?

Women are not miniature men. A new study in mice, published in Nature Communications in 2022, confirmed multiple sex differences in traits. “Ignoring these differences in some cases, such as measurements of blood cells, bones, and organs, can lead to significant loss of population variation in specific traits: up to 32 percent in women and 46 percent in men.” This complexity means that we need to consider gender differences in drug dosage on a case-by-case basis.” “They wrote.

It would be ideal, of course, to collect data on sex differences at the beginning of drug development, even before human drug trials begin. But Tang Zhijia said, “From the clinical practice, there is no condition to do this thing.” Our primary concern is usually liver and kidney function.”

At this stage, it is more based on clinical experience to adjust the drug regimen for drugs with gender differences.

Women, in the medical field

For a long time, in drug experiments and biological experiments, men are generally dominant, and women are less likely to participate in clinical trials.

Part of the reason is that researchers worry about women’s menstrual cycles, hormonal fluctuations, and so on affecting the final outcome of clinical trials. In addition, pregnant women are often excluded from trials for ethical and safety reasons.

In 1985, the United States released the Public Health Services Report on Women’s Health, which noted that a historical lack of research on women’s health has undermined the quality of health information available to women and the health services they receive.

Then, in 1993, the U.S. Food and Drug Administration issued guidelines requiring that clinical studies of drugs intended for both sexes include equal numbers of male and female subjects. It wasn’t until 2016 that China explicitly included women in a Bioequivalency (BE) trial for the first time. BE test is an important part of consistency evaluation and application and registration of generic drugs, mainly used to evaluate the quality of generic drugs.

So what happens to women in clinical trials now that these regulations have been proposed?

Not only in experiments, but also in academic circles, there are differences between men and women.

On July 2, 2021, The Journal of the American Medical Association (JAMA) published a paper analyzing 5,554 medical papers published in top medical journals between 2015 and 2018, It is found that there is a big gap between female authors and male authors in the amount of papers published and the amount of application.

The lack of female researchers will affect the research on women’s health to some extent. Women have unique and different life experiences than men, so they need to be involved if basic research and medical inventions are to be developed for them.

Pregnant woman, is facing a drug dilemma

The lack of research on women’s health issues can undermine the quality of health information available to women and the quality of health services. The problem is even worse for women who need medication during pregnancy and breastfeeding.

Acetaminophen is considered one of the safest antipyretic drugs for pregnant women. Its pregnancy drug classification is class B, which is a safe level of medication. And acetaminophen, sold under the Tylenol brand name, has a special place in the pharmaceutical industry. Millions of people regularly use Tylenol to cope with illness.

But is it really safe for pregnant women? What does the instruction manual say?

Currently, multiple studies have linked acetaminophen to ADHD and autism spectrum disorder (ASD). In the United States, a lawsuit is being filed against Johnson & Johnson and various stores selling generic acetaminophen products, alleging that the drug sellers failed to warn that use of the drug during pregnancy could cause autism.

But due to research limitations, there is currently no strong evidence that acetaminophen use during pregnancy causes autism or ADHD in children. Some experts believe that acetaminophen has some effect on pregnancy and should only be used when necessary and in consultation with a doctor.

But if acetaminophen is avoided during pregnancy to treat fever or pain, it may also have negative effects on pregnant women.

Health problems during pregnancy remain a concern, in part because pregnant women have been excluded from drug clinical trials. Drug trials are likely to be harmful to pregnant women and their fetuses. But the lack of data on the safety and effectiveness of drugs for pregnant women also hurts them. At present, in some drug trials, pregnant women have also begun to be tested. But for ethical reasons, pregnant women are still excluded from most trials.

We still don’t have a definitive answer on how to deal with risks during pregnancy. Tang Zhijia said that the current drug policy for pregnant women is to try to keep the dosage as low as possible and do not use the drug. “Because there are quite a few drugs whose effects on the fetus are unclear. There is a lack of clinical trials to show whether it has any effect on the fetus.”

In the future, think more

It’s not just pregnant women, there are many groups of people who are ignored by most medical experiments, such as children and the elderly. Due to the lack of clinical studies, their medication is more dependent on the individual experience of the doctor, and much is still unknown about the possible effects of the drug on them.

We hope that in the future, in the development and research of drugs, all populations will be fully considered. It is important to provide safe medication for different groups of people, so that everyone knows how to use drugs properly.