How Do Painkillers Work?

By: Annabelle Clarke
May 11, 2021
(1 Comment)

The mechanism of action of a pain-reliever depends on the type of medication you are using. Different analgesics have different modes of action as they are formulated with varying active pharmaceutical ingredients (APIs). The API is the component of a medicine that is responsible for bringing about the therapeutic benefits.

Opioid tablets are those derived from the poppy plant and are useful for the management of moderate to moderately severe pain. The mode of action of opiates involves binding to the opioid receptors (located throughout the nervous and peripheral systems) and the subsequent blocking of pain perception. Opioid painkillers were prescribed 168 million times in 2018 alone, according to the Centres for Disease Control and Prevention (CDC).

Non-opioid pain medications are painkiller medications that are not of opioid derivation. An example of this class of analgesics includes paracetamol (acetaminophen). Commonly used by millions of adults and children around the world, these painkillers work by blocking the chemical messages in the brain that tell us we are experiencing pain. Non-steroidal anti-inflammatory drugs (NSAIDs) painkillers target inflammation, fever and pain by inhibiting the action of the cyclooxygenase enzymes, specifically COX-1 and COX-2.

How Do Painkillers Know Where to Target?

Pain medications are actually unaware of where to travel to the body, but rather it is the body that directs the analgesic to its site of action.
When you swallow a pain-relieving tablet, the pill travels from the oesophagus to the stomach before reaching the small intestine. Once broken down by the liver, the active ingredient is absorbed into the bloodstream where it can bring the therapeutic pain-relieving effects to prominence.
Each pain tablet is created to target certain proteins in the body, known as receptors. For example, opioid analgesics target and bind to opioid receptors. When discomfort is felt, the API travels through the blood to seek out specific receptors that are generated by pain, and once bound to the receptor, the therapeutic can then bring into effect the relief of pain.
Likewise, pain medications can also bind to other locations in the body other than the targeted sites. This is the reason behind the possible painkiller side effects, which are secondary effects of a medication that occur when a therapeutic does more than it is intended to. Adverse effects happen because it is difficult to design a medication to target one area of the body, without affecting another.

How Long Do Painkillers Take to Work?

The onset of action (how long a medication takes to work) depends on the type of painkiller you are using.
Short-acting pain medicines are typically those with a short duration of action and can be in the form of immediate-release tablets. These painkillers start to work quickly but the pain relief effects generally do not last for long.
Long-acting analgesics come in the form of extended-release pills. These therapeutics are controlled-release pills designed to bring about prolonged pain relief. The benefits of controlled-release painkillers last for much longer and this allows for reduced dose frequencies.
In a study comparing the effects of short and long-acting opioid medications, Argoff et. al. (2009) suggests that both types of pain-relievers can be effective for the management of pain symptoms but long-acting opiates are generally superior for treating a particular chronic non-cancer pain symptom.

This study went on to add that long-acting analgesics are typically more stable and require less frequent dosing, but the treatment should be tailored to the individual and their specific pain state.

How Long Does It Take Painkillers to Leave Your System?

For a medication to be eliminated from the body, it has to be first metabolised. This is the breakdown of the therapeutic into its metabolites. Most of the metabolites are excreted via the kidneys, but there are other processes involved in drug elimination as well, such as through bile, faeces, urine etc. The time it takes for painkillers to be removed from the body is dependent on the formulation of the analgesic.

Certain pain-relievers can be eliminated from the body rapidly and these are usually the short-acting forms of pain medicines. Short-acting painkillers leave your system within hours of your last dose. The long-acting pain tablets commonly take longer to leave your system, because these pills can sometimes take anywhere from 24 to 48 hours to work, before they can be removed from the body.

The elimination of a painkiller dosage from the body also depends on certain factors specific to an individual and these can include:

Age: senior individuals tend to have impaired liver and kidney functioning, which may prolong drug elimination
Gender: women tend to have a slower clearance of medications via the kidneys
Medical condition: those with renal or hepatic dysfunctions can have impaired drug elimination processes

What Painkillers Can You Take When Pregnant?

It is widely known that you cannot take many medications when you are pregnant, but there are some analgesics that can be used safely when you experience symptoms of discomfort.
In most cases, therapeutics are not recommended during pregnancy as the safety of the medicine has not been established and there is insufficient evidence of how the medicament can affect the unborn baby.
Most pregnant women are prescribed non-opioid pain tablets as this may be the best painkiller with regard to safety. In fact, in a U.S study it was found that almost two-thirds of women were prescribed acetaminophen during their nine month gestational period. However, this also comes with significant risk.
A 2019 study reported that babies exposed to high levels of acetaminophen in the womb were at higher risk of being diagnosed with ADHD (attention deficit hyperactivity disorder) and/ or autism.

Other pain-relieving medications are safe for use depending on the gestational period. For example, the Food and Drug Administration (FDA) recommends NSAIDs up until 20 weeks of gestation, but these painkillers are not advised in the second half of pregnancy.
The general rule of thumb is that pregnant women can use a pain medication advised by a medical practitioner provided that the benefits of treatment outweigh the risks.
Pregnant women who are unable to travel can easily buy painkillers in the UK through credible online pharmacies.