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I'll start out strong and let you know that paracetamol overdose is the number one childhood admission to the hospital. From 2004 to 2017 the rate of intentional overdose increased by 77%. Overdose symptoms include: diarrhoea, increased sweating, loss of appetite, nausea, vomiting, stomach cramps, swelling, pain, tenderness in upper abdomen. It is the most common reason for acute liver failure in many countries, but usually not from sticking to the recommended doses. "Toxicity is influenced by age, comorbidities, alcohol use, nutritional status (such as malnourishment), concurrent medicine use (including herbal medicines) and genetics" [1]. The Australian Institute of Health and Welfare [2] admit that 63% of poisoning cases among youth ages 10-24 were actually intentional self-harm (not paracetamol specific). While this is alarming, there is more to consider than just drug overdose when it comes to paracetamol.
It's one of the most commonly used pain medications in the world. Paracetamol, or acetaminophin, theoretically works by activating the descending serotonergic pathways, blocking COX-2, and inhibiting endocannabinoid reuptake. Although this mechanism is not deeply understood. Paracetamol is often used to dull pain, as an alagesic. This is not to be confused with ibuprofen, which is used as an anti-inflammatory agent. Through my work I have noted that many people do not understand this difference and it can mean they may choose the wrong medication for their situation. It would not be suitable, for example, in an inflammatory condition like rheumatoid arthritis [3]. McCrae et, al. [3] note that long-term, chronic use of paracetamol can lead to some nasty side effects. Let's take a look through pregnancy and a few body systems.
Cardiovascular effects
There was a brief evidence that paracetamol use increased systolic blood pressure (by 4mmHg), which may cause 10-20% increase in risk of stroke, and 7-14% increase in risk of ischaemic heart disease [3]. So far, this has not been substantiated. Observationally, long term use of paracetamol is connected with an increased risk of hypertension, especially daily dosing.
Respiratory effects
There have been several reports of Aspirin causing disease complications, but paracetamol? Some recent evidence came to light regarding Asthma and paracetamol use. Observational studies do show a distinct connection between paracetamol use and diagnoses or exacerbation of asthma [3]. Wether this is due to the preexisting recurrent infections and illness that are common before onset, or something else. Paracetamol metabolism uses glutathione, and glutathione depletion with increased oxidative stress could potentially change T helper physiology towards Th2 phenotype, and unbalance lipoxygenase activity. Basically your immune system malfunctions from the paracetamol, and there is a decrease in forced expiratory volume in those that are sensitive. Not all people with asthma reacted this way [3]. So far, there is no causational evidence between the two.
Gastrointestinal effects
Chronic use of paracetamol may contribute to nausea and dyspepsia, but gastrointestinal bleeding? The risk factor for gastrointestinal related hospitalisation when using paracetamol was higher in elderly patients, which is higher when using non-steroidal anti-inflammatory drugs (NSAIDs). Considering this adverse effect has only been noted with concommitent use, or with long-term daily use, I think most people's use of paracetamol wouldn't contribute.
Pregnancy
Paracetamol does cross the placenta, and neonates (foetus') process things differently. Depending on length of use, dosage and whether it's been used in the third trimester or not, can change the effects of paracetamol on neonates. "There is some evidence of increased risk with paracetamol use in pregnancy and neurodevelopmental disorders, respiratory illness and reproductive toxicity" [3]. Maternal use of paracetamol for more than 28 days during pregnancy has been highly linked with gross motor development, behaviour, and communciation. This is not highly understood, and therefore as of now cannot be called causal. The relationship between paracetamol and neonatal BDNF changes are being explored.
Additionally, there is some evidence that paracetamol use may affect the genetics of further generations. It is also unclear whether the use of paracetamol during a maternal fever affects the foetus. However, to make a confident assessment would require an exceptionally large body of evidence which just doesn't exist yet and is entirely unethical to test. The advice given is to avoid the use of paracetamol while pregnant, especially with fever, and avoid long-term use if possible.
There are several other methods to reducing pain, especially in pregnancy, which your GP should share as an alternative. You are entitled to be informed of these choices to ensure you are able to make fully informed decisions about your own health.
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