How do different painkillers work?

It’s easy to assume the only difference between painkillers is their strength. Or that any painkiller you can buy without a prescription is always safe to use, but that isn’t necessarily the case.

Remember, speak to your own doctor or pharmacist if you have any concerns or queries, and anybody with existing health problems, allergies, or who’s already taking other medications and supplements, should check that a drug is safe and suitable for them.

We asked pharmacists to explain how the most common painkillers work and the main points to keep in mind.

“Paracetamol is probably the most commonly used painkiller, and the one most people would try first,” says Sandra Gidley, president of the Royal Pharmaceutical Society.

A good all-rounder for relieving general aches and pains, paracetamol can also help reduce a fever. “It’s been used for about 100 years, but we still don’t understand exactly how it works,” says Ms Gidley. “We think it helps relieve pain by decreasing the amount of a substance called prostaglandin.” Prostaglandins are produced by the brain and spinal cord in response to injury or disease, for example. They stimulate nerve endings, causing us to experience pain.

The important stuff

Compared with other drugs, paracetamol isn’t associated with many side-effects – providing it’s used appropriately. It’s very important not to exceed the maximum recommended dosage (which for adults is up to eight 500mg tablets within any 24-hour period), as overdosing can happen quickly, and potentially cause devastating damage.

“People think, ‘Oh, it’s only paracetamol’, but if you take too many, it can be dangerous,” explains Ms Gidley, who says even slightly exceeding the recommended dose can lead to symptoms of paracetamol poisoning. “The damage to your liver can be awful,” she adds.

If you’re taking any other medications alongside paracetamol, check the packets, as a number of other over-the-counter medications – for instance, cold and flu remedies – can also include paracetamol. If you’re ever unsure, speak to your pharmacist.

Read more: Most common questions pharmacists are asked

Another important thing to be aware of is the risk of ‘medication overuse headache’ or ‘rebound headache’. This is a vicious cycle where people who take painkillers to help manage headaches, end up developing a worse or chronic headache as a result. This doesn’t just apply to paracetamol, but other types of painkiller too.

If you are taking painkillers regularly, check in with your doctor – especially if you have chronic headaches that aren’t getting better. You may really need a referral to a specialist who can ensure you’re being treated appropriately, or guidance for breaking the ‘rebound headache’ cycle. Ms Gidley advises trying self-help strategies and relaxation techniques to help take the edge off.

Non-steroidal anti-inflammatories
Ibuprofen, another commonly used over-the-counter painkiller, is a member of the non-steroidal anti-inflammatory (NSAID) family. These also work by altering chemical activity within the body, but also reduce inflammation – which can make them particularly good for things like joint pain and injuries.

“There are a number of other NSAIDs, but they’re not all available over the counter,” says Ms Gidley, who explains this is because of the risks and side-effects they’re associated with. Higher strength NSAIDs (such as naproxen and diclofenac) may be prescribed to help a number of conditions, but it’s important they’re appropriately managed and reviewed with your doctor.

The important stuff
“Although widely used, NSAIDs are not right for everybody,” says Ms Gidley. “For example, for some people with asthma, NSAIDs can provoke an asthma attack. Some have also been found to have a negative effect on the heart and they may not be a good idea for people with high blood pressure. Prolonged use can also cause kidney disease, so we’re much more careful about the use [of NSAIDs] now.”

Read more: Painkillers like ibuprofen can increase the risk of heart disease

Another key point with NSAIDs is that they can cause stomach irritation, sometimes even leading to a stomach ulcer. This can be avoided by ensuring you take the tablets with food, as advised, and taking an accompanying medication to protect the stomach. “This is usually a PPI, a proton pump inhibitor,” says Ms Gidley. “This is really quite important, especially if you’re taking a lot of them.”

This group of drugs includes very strong painkillers such as morphine, and at the other end of the scale, codeine, which can be bought over the counter in a low-dose combination with paracetamol (co-codamol). “They are very useful for treating short-term severe pain. They work by basically blocking pain messages to the brain and also cause a euphoria effect, which helps people forget about their pain too,” explains Ms Gidley.

Other opioid painkillers are only available on prescription, including tramadol and fentanyl, which often comes in patches. While powerful, all opioid use – including co-codamol – should be very carefully managed and, says Ms Gidley, “treated with extreme caution”.

The important stuff
One of the biggest risks is addiction, which can sometimes happen very quickly. In recent years, opioid painkiller addiction has been a huge problem in the US, and there’s growing concern in other countries. Part of the problem, Ms Gidley explains, is that you can quickly “get used” to a certain dosage, so need more to feel the effects. “In my work as a community pharmacist, I have come across people who’ve become so addicted to prescription painkillers, they’ve had to go on a drug withdrawal program to come clean.” However, addiction services are not widely available, so people can end up in a vicious cycle.

There are other side-effects to be careful with too, such as drowsiness. “High doses can also depress your breathing and reduce your heart rate, and you can lose consciousness,” says Ms Gidley. “The depression of breathing is a particular concern for some people.”

Chronic nerve pain drugs
Prescription medications, such as gabapentin, pregabalin and amitriptyline, are sometimes used for managing certain types of nerve (neuropathic) pain. These drugs are traditionally used to treat conditions such as epilepsy and depression, but at a certain dose, can also be effective for more severe and complex neuropathic pain, including sciatica, fibromyalgia and complex regional pain syndrome.

“Traditional painkillers either reduce inflammation at the site of injury or reduce the sensations of pain centrally in the brain. However, these medicines are different and work by suppressing the nerve signals that carry pain messages, making them very effective for treating neuropathic pain,” says Phil Day, superintendent pharmacist at, who explains that, in some cases, damage can make nerves “over-active”, heightening pain sensation. “Gabapentin, pregabalin and amitriptyline, in particular, are prescribed more often these days for pain relief, than for epilepsy or depression.”

Read more: Why painkillers are being used for emotional relief

The important stuff
Mr Day notes that not all anti-depressants and epilepsy drugs work as painkillers, so it’s vital to only take them as prescribed. And while these medications can be very effective, they sometimes take a little while to ‘kick in’ and don’t work for everyone.

“As with all medicines, [these drugs] can have side-effects. Some can cause drowsiness, dizziness and weight changes, and they can clash with some other prescribed medicines, so this will need to be checked,” says Mr Day. “If they’re not working as well as expected, the doctor might increase the strength or dosage, or may change over to one of the other medicines.”

If any side-effects occur, check in with your doctor, and it’s always advisable to seek advice before you stop taking any prescribed medication.

Do you keep painkillers in the house? How often do you take them?

– With PA

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Written by YourLifeChoices Writers

YourLifeChoices' team of writers specialise in content that helps Australian over-50s make better decisions about wealth, health, travel and life. It's all in the name. For 22 years, we've been helping older Australians live their best lives.

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