Tag: paracetamol

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Paracetamol and Ibuprofen Linked to Antibiotic Resistance

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Study evaluated nine common medications used in old age care homes

Photo by Kampus Production

New research from the University of South Australia shows that the trusted staples of paracetamol and ibuprofen are quietly fuelling one of the world’s biggest health threats: antibiotic resistance.

In the first study of its kind, researchers found that ibuprofen and paracetamol are not only driving antibiotic resistance when used individually but amplifying it when used together.

Assessing the interaction of non-antibiotic medications, the broad-spectrum antibiotic ciprofloxacin, and Escherichia coli, researchers found that ibuprofen and paracetamol significantly increased bacterial mutations, making E. coli highly resistant to the antibiotic.

It’s an important finding that has serious health implications, particularly for people in aged care homes, where multiple medications are regularly administered.

The World Health Organization reports that antimicrobial resistance is a global threat to public health, and that bacterial resistance was directly responsible for 1.27 million global deaths in 2019.

Lead researcher UniSA’s Associate Professor Rietie Venter says the findings raise important questions about the risks of polypharmacy in aged care.

“Antibiotics have long been vital in treating infectious diseases, but their widespread overuse and misuse have driven a global rise in antibiotic-resistant bacteria,” Assoc Prof Venter says.

“This is especially prevalent in residential aged care facilities, where older people are more likely to be prescribed multiple medications – not just antibiotics, but also drugs for pain, sleep, or blood pressure – making it an ideal breeding ground for gut bacteria to become resistant to antibiotics.

“In this study we looked at the effect of non-antibiotic medicines and ciprofloxacin, an antibiotic which is used to treat common skin, gut or urinary tract infections.

“When bacteria were exposed to ciprofloxacin alongside ibuprofen and paracetamol, they developed more genetic mutations than with the antibiotic alone, helping them grow faster and become highly resistant. Worryingly, the bacteria were not only resistant to the antibiotic ciprofloxacin, but increased resistance was also observed to multiple other antibiotics from different classes.

“We also uncovered the genetic mechanisms behind this resistance, with ibuprofen and paracetamol both activating the bacteria’s defences to expel antibiotics and render them less effective.”

The study assessed nine medications* commonly used in residential aged care: ibuprofen, diclofenac, paracetamol, furosemide, metformin, atorvastatin, tramadol, temazepam, and pseudoephedrine.

Assoc Prof Venter says the study shows how antibiotic resistance is a more complex challenge than previously understood, with common non-antibiotic medications also playing a role.

“Antibiotic resistance isn’t just about antibiotics anymore,” Assoc Prof Venter says.

“This study is a clear reminder that we need to carefully consider the risks of using multiple medications – particularly in aged care where residents are often prescribed a mix of long-term treatments.

“This doesn’t mean we should stop using these medications, but we do need to be more mindful about how they interact with antibiotics – and that includes looking beyond just two-drug combinations.”

The researchers are calling for further studies into drug interactions among anyone on long-term medication treatment regimes so we can gain a greater awareness of how common medications may impact antibiotic effectiveness.

Source: University of South Australia

Categories : Obstetrics & GynaecologyTags :

Prenatal Paracetamol Use May Be Linked to Increased Risk of Autism and ADHD

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Researchers at the Icahn School of Medicine at Mount Sinai have found that prenatal exposure to paracetamol may increase the risk of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD), in children. The study, published in BMC Environmental Health, is the first to apply the rigorous Navigation Guide methodology to systematically evaluate the rigour and quality of the scientific literature.

Paracetamol (known as acetaminophen in the US and Canada) is the most commonly used over-the-counter pain and fever medication during pregnancy and is used by more than half of pregnant women worldwide. Until now, acetaminophen has been considered the safest option for managing headache, fever, and other pain. Analysis by the Mount Sinai-led team of 46 studies incorporating data from more than 100 000 participants across multiple countries challenges this perception and underscores the need for both caution and further study.

The Navigation Guide Systematic Review methodology is a gold-standard framework for synthesising and evaluating environmental health data. This approach allows researchers to assess and rate each study’s risk of bias, such as selective reporting of the outcomes or incomplete data, as well as the strength of the evidence and the quality of the studies individually and collectively.

“Our findings show that higher-quality studies are more likely to show a link between prenatal acetaminophen exposure and increased risks of autism and ADHD,” said Diddier Prada, MD, PhD, Assistant Professor of Population Health Science and Policy, and Environmental Medicine and Climate Science, at the Icahn School of Medicine at Mount Sinai. “Given the widespread use of this medication, even a small increase in risk could have major public health implications.”

The paper also explores biological mechanisms that could explain the association between acetaminophen use and these disorders. Paracetamol is known to cross the placental barrier and may trigger oxidative stress, disrupt hormones, and cause epigenetic changes that interfere with foetal brain development.

While the study does not show that paracetamol directly causes neurodevelopmental disorders, the research team’s findings strengthen the evidence for a connection and raise concerns about current clinical practices.

The researchers call for cautious, time-limited use of paracetamol during pregnancy under medical supervision; updated clinical guidelines to better balance the benefits and risks; and further research to confirm these findings and identify safer alternatives for managing pain and fever in expectant mothers.

“Pregnant women should not stop taking medication without consulting their doctors,” Dr Prada emphasised. “Untreated pain or fever can also harm the baby. Our study highlights the importance of discussing the safest approach with health care providers and considering non-drug options whenever possible.”

With diagnoses of autism and ADHD increasing worldwide, these findings have significant implications for public health policy, clinical guidelines, and patient education. The study also highlights the urgent need for pharmaceutical innovation to provide safer alternatives for pregnant women.

Source: Mount Sinai

Categories : New Compounds and TreatmentsTags :

Small Molecule Could Alleviate Paracetamol-induced Liver Injury

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Human liver. Credit: NIH

Paracetamol (acetaminophen) is one of the most common painkillers and is found in hundreds of different medications. While safe at recommended doses, paracetamol overdose is the leading cause of acute liver injury in the U.S. Now, researchers propose that a new molecule has the potential to treat acetaminophen-induced liver injury (AILI) and other inflammatory conditions. They conducted a small-scale mouse trial and found that the new compound decreased AILI-caused liver inflammation and prevented liver damage. 

Jannatun Nayem Namme, a graduate student at Virginia Commonwealth University, will present her team’s results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2025 is being held Aug. 17-21; it features about 9000 presentations on a range of science topics.  

Most acetaminophen overdoses are accidental, often due to people unintentionally consuming multiple products containing the painkiller or misinterpreting dosage. After taking a recommended amount of paracetamol, a person’s liver converts a small percentage of it into a toxic molecule called N-acetyl-p-benzoquinone imine (NAPQI). Normally, the liver can quickly metabolise NAPQI into a non-toxic form. But if a person takes too much acetaminophen, NAPQI builds up and causes irreversible cell damage, leading to liver injury or death. Currently, N-acetylcysteine is the only drug available to treat AILI, and it must be administered within eight hours of overdose. 

To develop novel treatments for inflammatory conditions, such as AILI, and neurodegenerative conditions, Namme and her colleagues previously focused on small molecules that reduce the activity of inflammation-causing proteins, known as inflammasomes. Inflammasomes are also involved in pyroptosis, a type of cellular death associated with AILI. While developing inflammasome inhibitors, the researchers noticed that some of the compounds they created could target a specific inflammatory protein called gasdermin D (GSDMD). GSDMD is involved in pyroptosis. 

Namme and the team synthesised several different GSDMD-inhibiting compounds and tested them for their ability to bind to GSDMD. They discovered that one small molecule, which they labelled YM81, selectively binds to and inhibits GSDMD from initiating pyroptosis.  

Next, the researchers treated five mice with AILI using YM81 and compared them to 10 mice given a placebo. They monitored the extent of liver damage in the animals 17 hours after the acetaminophen overdose. Compared to the placebo group, mice treated with YM81 had significantly lower levels of alanine transaminase and aspartate transaminase, two liver injury biomarkers. These results indicate that the YM81 treatment helped decrease liver inflammation by inhibiting GSDMD. 

Shijun Zhang, the study’s principal investigator, says that YM81 is in the early stages of drug development. “In the future, we will focus on optimising YM81 to increase its potency, safety and stability, in addition to exploring its therapeutic potential in additional animal models,” he says. 

Namme adds that GSDMD inhibitors like YM81 have the potential to treat other inflammatory conditions. “GSDMD is a common protein involved in multiple inflammatory and neurodegenerative diseases, such as arthritis, sepsis and gout,” she says. “Targeting GSDMD could offer a therapeutic strategy to reduce the inflammation and damage from multiple diseases and causes.”

Source: American Chemical Society

Categories : Pain ManagementTags :

Podcast: Paracetamol’s Newly Discovered Mechanism Could Unlock Powerful New Analgesics

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Credit: Pixabay CC0

Despite being used for decades as a pain reliever, paracetamol’s mechanism of action was never fully known. Now, new research from the University of Jerusalem points to an unexpected effect, one which may usher in a whole new era of analgesics.

In QuickNews’ first podcast, you can listen to a discussion on how a newly discovered mechanism of action for paracetamol helps it achieve its analgesic effect, and how this could be applied to the development of novel, highly specific pain relievers.

Categories : Neurology Pain ManagementTags :

Why Paracetamol Works: New Discovery Ends Longstanding Mystery

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A breakthrough study from the Hebrew University of Jerusalem, published this week in the prestigious journal PNAS (Proceedings of the National Academy of Sciences USA), reveals a previously unknown peripheral mechanism by which paracetamol relieves pain.

The study was led by Prof Alexander Binshtok from the Hebrew University’s Faculty of Medicine and Center for Brain Sciences (ELSC) and Prof Avi Priel from its School of Pharmacy. Together, they uncovered a surprising new way that paracetamol, one of the world’s most common painkillers, actually works.

For decades, scientists believed that paracetamol relieved pain by working only in the brain and spinal cord. But this new research shows that the drug also works outside the brain, in the nerves that first detect pain.

Their discovery centres on a substance called AM404, which the body makes after taking paracetamol. The team found that AM404 is produced right in the pain-sensing nerve endings – and that it works by shutting off specific channels (called sodium channels) that help transmit pain signals. By blocking these channels, AM404 stops the pain message before it even starts.

“This is the first time we’ve shown that AM404 works directly on the nerves outside the brain,” said Prof Binshtok. “It changes our entire understanding of how paracetamol fights pain.”

This breakthrough could also lead to new types of painkillers. Because AM404 targets only the nerves that carry pain, it may avoid the numbness, muscle weakness, and side effects that come with traditional local anaesthetics.

“If we can develop new drugs based on AM404, we might finally have pain treatments that are highly effective but also safer and more precise,” added Prof Priel.

Source: EurekAlert!

Categories : Pain ManagementTags :

Paracetamol and NSAIDs Best Non-opioid Drugs for Low Back Pain

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Photo by Sasun Bughdaryan on Unsplash

Acute low back pain is a common cause of disability, and while opioid drugs are effective at controlling pain, excessive use creates a great potential for substance abuse. An analysis in the Journal of Orthopaedic Research examined which non-opioid drugs are best for relieving this pain.

The analysis, which included all randomised controlled trials published to date (18 studies with 3478 patients), showed that muscle relaxants and non-steroidal anti-inflammatory drugs (NSAIDs) could effectively and rapidly reduce symptoms.

The combination of NSAIDs and paracetamol was associated with a greater improvement than NSAIDs alone.

“This is a first step towards the optimisation of the management of acute low back pain. However, specific patient characteristics such as having allergies and comorbidities must always be taken into consideration,” said lead author Alice Baroncini, MD, PhD, of RWTH University Hospital in Germany. “Further research will need to focus on the identification of the type of drugs that not only offer the best and quickest pain relief, but also show the lowest rate of symptom recurrence.”

Source: Wiley

Categories : Diseases, Syndromes and ConditionsTags :

Paracetamol May Protect Against Kidney Damage in Malaria

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Paracetamol may help protect against kidney damage in patients with malaria, according to a study recently published in Clinical Infectious Diseases.

The study found that for patients with severe malaria caused by the malaria parasite Plasmodium knowlesi (the most common cause of malaria in Malaysia), taking paracetamol regularly for 3 days led to improvements in kidney function when tested one week later.

The findings are important because they will help provide the best possible treatment to patients with severe malaria, said study leader Dr Daniel Cooper.

“Even minor kidney injury can have long-term effects, so anything we can do to minimise kidney injury from malaria will be beneficial for these patients’ long-term outcomes,” Dr Cooper said.

In collaboration with international partners, the study involved 396 people with knowlesi malaria in Sabah, Malaysia.

Assistant Professor Bridget Barber said that in severe malaria, red blood cells can rupture, releasing haemoglobin which can have a toxic impact on kidneys, and it is now believed that paracetamol can help to mitigate these toxic effects.

“These results are consistent with other studies conducted in patients with other forms of malaria, including in adults in Bangladesh, and in children in Africa. Importantly, these findings also suggest that paracetamol may help to protect the kidneys in other conditions that are also associated with rupture of red blood cells,” A/Prof Barber said.

Source: MedicalXpress

Categories : Cardiovascular DiseaseTags :

CVD Risk Warning for Paracetamol That Contains Sodium

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Graphical abstract from European Heart Journal editorial: sodium hidden in medication warrants warning labels by drug companies

Clinicians have recommended avoiding effervescent, soluble paracetamol that contains sodium, following findings from a large study that shows a link with a significantly increased risk of cardiovascular disease (CVD) and mortality in people who have hypertension and even in people with normal blood pressure.

The study of nearly 300 000 patients registered with UK GPs was published in the European Heart Journal.

Sodium is often used to help drugs such as paracetamol dissolve and disintegrate in water. However, effervescent and soluble formulations of 0.5g tablets of paracetamol can contain 0.44 and 0.39g of sodium respectively. If a person took the maximum daily dose of two 0.5g tablets every six hours, they would consume 3.5 and 3.1g of sodium respectively – a dose that exceeds the WHO-recommended total daily intake of 2g a day. In 2018, 170 people per 10 000 of the population in the UK were using sodium-containing medications, with a higher proportion among women. There are alternative formulations that contain little or no sodium.

Excessive salt in the diet remains a major public health problem and is associated with an increased risk of cardiovascular disease (CVD) and death among patients with hypertension. However, there is inconsistent evidence showing an increased risk in normotensive individuals.

Professor Chao Zeng led a team which analysed data from a medical database of UK GPs’ records. They looked at 4532 hypertensive patients who had been prescribed sodium-containing paracetamol and compared them with 146 866 hypertensive patients who had been prescribed sodium-free paracetamol. They also compared 5351 normotensive patients who were prescribed sodium-containing paracetamol with 141 948 normotensive patients prescribed sodium-free paracetamol. The patients were aged 60-90 years and followed up for one year.

The researchers found the risk of heart attack, stroke or heart failure after one year for patients with high blood pressure taking sodium-containing paracetamol was 5.6% (122 cases of CVD), while it was 4.6% (3051 CVD cases) among those taking sodium-free paracetamol. Mortality risk was also higher; the one-year risk was 7.6% (404 deaths) and 6.1% (5510 deaths), respectively.

A similar increased risk was seen among normotensive patients. Among those taking sodium-containing paracetamol, the one-year CVD risk was 4.4% (105 cases of CVD) and 3.7% (2079 cases of CVD) among those taking sodium-free containing paracetamol. The risk of dying was 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.

Prof Zeng said: “We also found that the risk of cardiovascular disease and death increased as the duration of sodium-containing paracetamol intake increased. The risk of cardiovascular disease increased by a quarter for patients with high blood pressure who had one prescription of sodium-containing paracetamol, and it increased by nearly a half for patients who had five or more prescriptions of sodium-containing paracetamol. We saw similar increases in people without high blood pressure. The risk of death also increased with increasing doses of sodium-containing paracetamol in both patients with and without high blood pressure.”

Prof. Zeng said that clinicians and patients should be aware of the risks associated with sodium-containing paracetamol and avoid unnecessary consumption, especially when the medication is taken for a long period of time.

“Given that the pain relief effect of non-sodium-containing paracetamol is similar to that of sodium-containing paracetamol, clinicians may prescribe non-sodium-containing paracetamol to their patients to minimise the risk of cardiovascular disease and death. People should pay attention not only to salt intake in their food but also not overlook hidden salt intake from the medication in their cabinet,” he said.

“Although the US Food and Drug Administration requires that all over-the-counter medications should label the sodium content, no warning has been issued about the potentially detrimental effect of sodium-containing paracetamol on the risks of hypertension, cardiovascular disease and death. Our results suggest re-visiting the safety profile of effervescent and soluble paracetamol.”

Being an observational study it can only show only that there is an association between salt in paracetamol and CVD and deaths, rather than that salt causes these events. Other limitations include a lack of data on dietary intake of salt and excretion of salt from urinary samples. The use of over-the-counter paracetamol was not also recorded, however by restricting the study to those over 60 who qualify for free prescriptions in the UK, the risk of this is minimised.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Hypertension Warning for Long-term Paracetamol Use

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BP cuff for home monitoring, Source: Pixabay

Long-term paracetamol use could increase the risk of heart disease and strokes in people with high blood pressure, according to a randomised clinical trial by the University of Edinburgh.

Researchers recommend that patients with a long term prescription, usually for chronic pain, should rather choose the lowest effective dose for the shortest possible time.

The study, which appears in Circulation, is the first large randomised clinical trial to address the question of paracetamol’s effect on cardiovascular disease, and complements earlier work in observational studies.

Paracetamol was often suggested as a safer alternative to non-steroidal anti-inflammatory drugs (NSAIDs), which are known to increase blood pressure and risk of heart disease.

In the latest study, 110 patients with a history of high blood pressure were prescribed one gram of paracetamol four times a day – a routinely prescribed dose in patients with chronic pain – or a matched placebo for two weeks. All patients received both treatments, with the order randomised and blinded. The paracetamol group saw a significant increase in blood pressure, compared to the placebo group.

This rise was similar to that seen with NSAIDs, and could be expected to increase the risk of heart disease or stroke by around 20%. The findings should lead to a review of long-term paracetamol prescriptions to patients, said the researchers, especially to those with hypertension and an increased risk of heart disease or stroke.

Lead Investigator Dr. Iain MacIntyre said: “This is not about short-term use of paracetamol for headaches or fever, which is, of course, fine—but it does indicate a newly discovered risk for people who take it regularly over the longer term, usually for chronic pain.”

Principal Investigator Professor David Webb said: “We would recommend that clinicians start with a low dose of paracetamol, and increase the dose in stages, going no higher than needed to control pain. Given the substantial rises in blood pressure seen in some of our patients, there may be a benefit for clinicians to keep a closer eye on blood pressure in people with high blood pressure who newly start paracetamol for chronic pain.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, who funded the study, said: “This research shows how quickly regular use of paracetamol can increase blood pressure in people with hypertension who are already at increased risk of heart attacks and strokes. It emphasises why doctors and patients should regularly review whether there is an ongoing need to take any medication, even something that may seem relatively harmless like paracetamol, and always weigh up the benefits and risks. However, if you take paracetamol occasionally to manage an isolated headache or very short bouts of pain, these research findings should not cause unnecessary concern.”

Source: University of Edinburgh

Categories : Obstetrics & GynaecologyTags :

Consensus Statement Cautions on Paracetamol Use in Pregnancy

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Source: Anna Hecker on Unsplash

A consensus statement by 13 doctors in different countries suggests that pregnant people only take paracetamol/acetaminophen if it is medically necessary, Their paper, published in the journal Nature Reviews Endocrinology, the group paracetamol/acetaminophen (APAP). 

In the same journal issue, an accompanying Editorial outlines the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.

Research in recent years has shown that it is possible under some circumstances for APAP to alter foetal development which can herald problems with neurological, urological and reproductive disorders in the baby – the authors found evidence of birth defects in 26 out of 29 studies. The authors call for more research into the possible problems with the drug’s use by pregnant women. They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre site – that APAP is the only pain management drug available for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby –  such as having a fever. But they also note that pregnant women’s APAP use appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose painkiller.

The expert group and the authors of the new paper notably both point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.

The consensus statement’s authors say their intention behind the article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise. They note that current research has shown, for example, that the risk of harm seems to rise as the duration of APAP use goes up. In light of this, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.

Source: Medical Xpress