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Non-steroidal anti-inflammatory drugs (NSAIDS)

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Non-steroidal anti-inflammatory drugs (NSAIDS)



Introduction 
 


Non-steroidal anti-inflammatory drugs (NSAIDS)



 

Non-steroidal anti-inflammatory drugs (NSAIDs) are a medication widely used to treat a range of conditions.

NSAIDs are used to:



relieve pain



reduce inflammation (redness and swelling)



bring down a high temperature (fever)



Common acute (short-term) conditions that can be treated with NSAIDs include:



headaches



painful periods



toothache



soft tissue injuries such as sprains and strains



infections, such as the common cold or the flu (NSAIDs do not treat the underlying infections, but can help to relieve symptoms; especially fever)



Common chronic (long-term) conditions that can be treated with NSAIDs include:



most types of arthritis, including rheumatoid arthritis, other forms of inflammatory arthritis and osteoarthritis



chronic back pain



chronic neck pain



Things to consider when using NSAIDs

NSAIDs are associated with a small increase in the risk of a person experiencing a heart attack, stroke or heart failure. These risks are related to how long they are used for, the dosage and certain types of NSAIDs.

NSAIDs are only used in people who have an existing high risk of developing these types of conditions if there are no suitable alternatives and the medications bring significant benefit.

High-risk groups include:



those with a history of previous heart attack, stroke or heart failure



people aged 75 or over



people with diabetes



smokers



people with high blood pressure



NSAIDs are also not usually recommended for people who:



are pregnant or breastfeeding



have a history of significant kidney disease



have a history of significant liver disease



have active stomach ulcers (a sore in the lining of the stomach), or are at high risk of developing stomach ulcers



For people who are unable to take NSAIDs for medical reasons, the painkiller paracetamol can be used as an alternative. For more severe pain, prescription painkillers, such as codeine or tramadol, can be tried. It can be difficult to find the perfect painkiller for each individual.

In cases of severe inflammation an injection of steroids (corticosteroids) can often help.

 

Side effects

Most people take NSAIDs without having any side effects. Short term use is unlikely to cause significant problems, especially in younger patients.

If side effects do occur they usually affect the stomach and intestines (gastrointestinal tract) and can include:



indigestion



stomach ulcer



allergic reactions



Proton pump inhibitors (PPIs) or H-2 antagonist (medications to suppress stomach acid) are often prescribed in combination with NSAIDs to reduce the risk of stomach ulcer complications for:



older patients (aged over 55)



people who have had previous stomach ulcers



people who need long-term NSAID treatment



Interactions

It is very important to read the patient information leaflet that comes with your medication as some NSAIDs can either react unpredictably with other medications, or make them less effective.

For example, it's usually not recommended to take an NSAID if you're also taking medication to prevent blood clots such as low-dose aspirinor warfarin. NSAIDs might still be prescribed by a health professional in certain circumstances.

Dosage

NSAIDs are available in:



tablet or capsule form



as a topical treatment (a cream, gel or lotion rubbed into a specific part of the body)



eye drops – used to treat eye pain



injections



Less commonly, NSAIDs are used as a suppository – a capsule inserted into the rectum (back passage).

NSAIDs that dissolve in water should only be taken long-term if prescribed by a health professional. This is because they contain a lot of sodium, which can increase your risk of high blood pressure or stroke over time.

It's important to strictly follow all of the instructions about the recommended dosage for your particular NSAID. If you exceed the recommended dose, you risk experiencing a wide range of adverse effects, some of which can be serious.

Names

In Europe, the most commonly prescribed NSAIDs are:



diclofenac



ibuprofen



naproxen



celecoxib



mefenamic acid



etoricoxib



indometacin



aspirin (in doses greater than 600mg)



Most of the NSAIDs listed above are generic medicines. This means that their production and distribution is not limited to a single company. Therefore, they are available under a range of different brand names and are cheaper to buy.

Some NSAIDs are available over the counter for short-term use only, without the need for a prescription. These NSAIDs include aspirin, diclofenac, naproxen and ibuprofen.

However, because a medication is available over the counter it does not mean it's safe or suitable for everyone. Again, it's important to read the patient information leaflet that comes with your medication.

It is generally accepted that naproxen is the safest NSAID with regard to heart attacks and strokes, but it's not clear how safe it is for the stomach. Celecoxib is the safest with regard to stomach problems, but it's not clear how safe it is on the cardiovascular system.

It's recommended that people taking NSAIDs try periods of not taking them to see if they're still needed.

Note: Aspirin must not be given to children under 16 unless directed by a doctor. Also, some people with asthma get attacks triggered by aspirin or NSAIDs.

How NSAIDs work 

Non-steroidal anti-inflammatory drugs (NSAIDs) work by interfering with particular enzymes in your body.

Enzymes are a special type of protein which help to bring about, or speed up, a chemical reaction within your body. For example, digestive enzymes help your digestive system break up large food particles into smaller pieces so your body can absorb them.

There are many enzyme systems in the body. One enzyme system involved in inflammation and pain is called the cyclo-oxygenase system.

Cyclo-oxygenase

NSAIDs interfere with an enzyme called cyclo-oxygenase (COX). Different parts of your body have different types of COX enzymes, which control the production of chemicals called prostaglandins. Different prostaglandins have different functions.

For example, the stomach contains a sub-type of COC called COX. This enzyme controls the production of substances called prostaglandins that help protect the stomach from acid (which is normally present in the stomach). Another sub-type called COX-2 enzymes are mainly activated during infection, injury or inflammation, and produce the prostaglandins involved in pain and inflammation.

NSAIDs can reduce pain and inflammation by preventing COX enzymes releasing the prostaglandin chemicals that cause pain and inflammation. However, prostaglandins carry out many different functions within your body. Interfering with them can cause a number of side effects, such as indigestion, inflammation of the stomach lining and stomach ulcers.

COX-2 inhibitors

To prevent side effects, researchers developed a new 'family' of NSAIDs known as COX-2 inhibitors.

These are designed to block the enzymes that cause pain and inflammation but avoid blocking the enzymes that protect the stomach lining. This helps reduce the risk of indigestion and stomach ulcers.

 

Although COX-2 inhibitors have less effect on the stomach, they might be more likely than traditional NSAIDs to cause side effects to the heart. Further research into this issue is ongoing. This means they may be more suitable for someone at risk of developing stomach or intestinal problems, but less suitable for those with a heart or circulation problem.

Special considerations 

 

There are a number of situations where the use of non-steroidal anti-inflammatory drugs (NSAIDs) is not recommended.

In some cases, they should only be used if you are directly instructed to by your GP or another qualified healthcare professional.

When to avoid NSAIDs

 

Children under 16 years old

Aspirin should never be given to children under 16 years of age because there is a small risk it could trigger a serious and potentially fatal condition called Reye’s syndrome. This condition can cause liver and brain damage. Paracetamol or ibuprofen are safer alternatives for children under 16.

Pregnant women

The use of NSAIDs during pregnancy is not recommended unless paracetamol does not effectively treat a particular condition. If an NSAID needs to be used, ibuprofen is the safest NSAID to use during pregnancy. If possible, it's best to avoid taking any medication during pregnancy for minor conditions.

However, it should be taken at the lowest possible dose to treat symptoms for the shortest possible time. NSAIDs, including ibuprofen, should never been taken from the 30th week of pregnancy onwards. This is because it can cause a dangerous rise in blood pressure (pulmonary hypertension) inside the lungs of the baby.

Breastfeeding women

The use of NSAIDs during breastfeeding is not recommended unless it is felt that the benefits of treatment outweigh the risks to your baby. If an NSAID is to be used, ibuprofen will be recommended at the lowest possible dose for the shortest possible time needed to treat your symptoms.

Asthma

Some people with asthma find that taking an NSAID can make their asthma symptoms more severe. If this happens to you, it is best to avoid taking NSAIDs in future (unless directly instructed to by your GP or other qualified health professional), and take paracetamol instead.

Allergic reaction

If you experience an allergic reaction after taking an NSAID (including aspirin), such as swelling of your eyes and lips (angioedema) or a severe skin rash, you should avoid taking NSAIDs in the future.

Cautions

Stomach ulcers

NSAIDs can increase your risk of developing stomach ulcers and experiencing internal bleeding, particularly if taken on a long-term basis. Therefore, if you have an increased risk of developing stomach ulcers and internal bleeding, you may wish to use an alternative medication –Things that increase your risk of developing stomach ulcers and internal bleeding include:



being 55 years of age or older



having a history of stomach ulcers or internal bleeding inside your digestive system



taking another medication known to increase the risk of stomach ulcers and internal bleeding



Medications known to increase the risk of stomach ulcers and internal bleeding include:



heparin and warfarin, which are used to prevent blood clots



aspirin, including low-dose aspirin



corticosteroids, used to treat inflammation and suppress the immune system



the two antidepressants known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)



However, there are some health conditions for which long-term use of NSAIDs may be the only effective method of relieving symptoms. For example:



persistent back pain



rheumatoid arthritis



osteoarthritis



certain other forms of arthritis



If you need to take NSAIDs on a long-term basis and have an increased risk of developing stomach ulcers and bleeding, you will probably be given an additional medication known as a proton pump inhibitor (PPI) or an an H-2 antagonist.

PPIs and H-2 antagonists help to prevent stomach ulcers and internal bleeding by reducing the production of stomach acid. See treating stomach ulcers for more information about PPIs and H-2 antagonists.

If you are taking an NSAID, avoid smoking and drinking large amounts of alcohol as these activities can increase your risk of developing stomach bleeding.

Cardiovascular and kidney conditions

In rare cases, NSAIDs can damage the kidneys and cardiovascular system (the heart and blood vessels).

The use of NSAIDs is not usually recommended for people who have an increased risk of developing cardiovascular or kidney conditions. Examples of these include:



having heart failure



having advanced chronic kidney disease



having a previous history of heart disease or heart attack



Liver disease

If you have liver disease then NSAIDs may not be suitable for you.

Some types of liver disease include:



alcoholic liver disease – where the liver becomes damaged by alcohol misuse, which in severe cases, can result in cirrhosis(scarring of the liver)



hepatitis – inflammation of the liver which is often the result of a viral infection, but can also be non-viral



liver failure – where the liver loses most, or all, of its functioning capability



 

Fertility advice

Long-term use of NSAIDs has been suggested by some studies to adversely affect women’s fertility. So you may wish to avoid taking them if you are a woman trying for a baby.

Side effects of NSAIDs 

Many people take non-steroidal anti-inflammatory drugs (NSAIDs) without having any side effects. They can be a very effective form of treatment and are widely used to treat a number of conditions.

However, it is important to remember that any medicine can carry a risk of side effects. In a small number of cases, the side effects of NSAIDs can be extremely serious. So if you are taking NSAIDs for a prolonged period of time, or in high doses, your reaction to the medication should be monitored.

Some of the side effects that can be caused by NSAIDs are described below.

Common side effects

NSAIDs most commonly affect the gastrointestinal tract (the stomach and intestines). Common side effects associated with the long-term use of NSAIDs include:



indigestion



stomach ulcer (a sore in the lining of the stomach)



increased blood pressure



Stomach ulcers can sometimes cause more serious complications, such as:



gastrointestinal bleeding – internal bleeding within the digestive system



anaemia – where blood is unable to carry enough oxygen around your body which can cause shortness of breath and tiredness



gastrointestinal perforation – where a hole occurs in the wall of your stomach or intestines



Less common side effects

Research has found that taking NSAIDs on a daily basis causes persistent headaches in around one in 10 people.

Some types of NSAID can make people feel drowsy or dizzy. If you have these side effects while taking an NSAID, avoid driving or using tools and machinery.

Rare side effects

In rare cases, NSAIDs can affect your heart and the rest of the circulatory system. Side effects can include:



heart failure – the heart is having trouble pumping enough blood around the body



heart attack



hypertension (high blood pressure that needs treatment)



stroke



making pre-existing inflammatory bowel disease (IBD) worse



Although these side effects are potentially very serious, it is important to note they are rare and most likely to affect someone who has an existing cardiovascular condition.

This is why NSAIDs are not usually recommended for people with a history of these types of condition.

If the use of an NSAID is thought to be vital, then naproxen is thought the safest choice when taken alongside a PPI or H-2 antagonist.

Additionally, NSAIDs may affect your liver or kidneys. Again, this only happens in a small number of cases, and is most likely to affect those with existing liver or kidney conditions.

 

Reporting side effects

The Yellow Card Scheme allows you to report suspected side effects from any type of medicine you are taking. It is run by a medicines safety watchdog called the Medicines and Healthcare Products Regulatory Agency (MHRA). See the Yellow Card Scheme website for more information.

Interactions  

You may not always be able to take non-steroidal anti-inflammatory drugs (NSAIDs) in combination with other medicines. This is because some combinations of medicines can cause harmful side effects.

Taking NSAIDs can also make certain medicines less effective. This could be potentially dangerous if these other medicines are treating a serious condition, such as high blood pressure (hypertension).

Some commonly used medications known to interact with NSAIDs are outlined below.

(This is not a complete list; always carefully read the information leaflet that comes with your medication in case there are other interactions that apply to you).

Low-dose aspirin

Low-dose aspirin is given as a preventative treatment to thin the blood in people thought to be at risk of a blood clot which could then trigger a heart attack and stroke.

The use of NSAIDs are not usually recommended for people taking low-dose aspirin because:



NSAIDs can make the aspirin less effective in thinning the blood



the combination of the two medications can increase the risk of stomach ulcers forming



If the use of an NSAID is thought to be absolutely necessary then you may be switched to an alternative blood thinning medication such asclopidogrel. This will require an H-2 antagonist to also be prescribed as PPIs cannot be used with clopdorel.

Ciclosporin

Ciclosporin is a medication used to treat autoimmune conditions such as arthritis or ulcerative colitis.

It is also used in people who have received an organ transplant to prevent their body rejecting the transplant.

There is a small risk of experiencing kidney and liver damage if you take NSAIDs while also taking ciclosporin.

So if you need to take both medications at the same time you may be referred for regular blood tests so the state of your liver and kidneys can be assessed.

Diuretics

Diuretics are a group of medications that help remove fluid from the body and are often used in the treatment of high blood pressure.

Diuretics are generally safe to take in combination with NSAIDs but you will need to be monitored as they can occasionally cause kidney damage and also lead to a rise in blood pressure.

Lithium

Lithium is a type of medication used to treat bipolar disorder and severe depression.

Taking NSAIDs in combination with lithium can disrupt the body’s ability to remove lithium from the body which can lead to a dangerous build-up of lithium levels.

If using NSAIDs is thought to be absolutely necessary, your dosage of lithium may need to be reduced and you will need regular blood tests to check lithium levels.

You should be alert for the symptoms of lithium poisoning, which include:



ataxia (loss of balance and co-ordination)



blurred vision



dizziness



muscle twitching



tinnitus (ringing in your ears)



Methotrexate

Methotrexate is a medication used to treat rheumatoid arthritis. Seek advice from a doctor before taking methotrexate alongside NSAIDs.

Phenytoin

Phenytoin is a medication used to treat epilepsy. Seek advice from a doctor before taking phenytoin alongside NSAIDs.

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are a group of medications used to treat depression as well as a number of other mental health conditions, such as anxiety disorder and obsessive compulsive disorder.

There is evidence that taking SSRIs in combination with an NSAID can increase the risk of a person experiencing bleeding inside their digestive system. It's likely that long-term use will also require a PPI or H-2 antagonist to be prescribed to reduce this risk.

The risk is thought to be small, but as a precaution you should be alert for signs that bleeding has taken place.

Depending on the location and type of blood vessel, you may have long-term bleeding which could lead to anaemia. Symptoms of anaemia include:



fatigue (feeling tired all the time)



shortness of breath



pale skin



irregular heartbeats



Alternatively, the bleeding can be rapid and massive, causing you to vomit blood or pass stools that are black and tar-like.

Warfarin

Warfarin is a medication used to treat people with a history of blood clots, or those thought to have a high risk of developing blood clots at a later date.

The use of NSAIDs is not usually recommended for people taking warfarin as it can enhance the effects of the medication and make you prone to excessive bleeding. In rare cases, a specialist may prescribe this combination.

Alcohol

It is usually safe to drink alcohol while taking an NSAID, as long as you stick to the recommended daily limits (three to four units of alcohol a day for men, and two to three units for women).

Drinking more than the recommended daily limit of alcohol may irritate your stomach lining. Therefore, you may be unable to take NSAIDs if you are going to drink more than the recommended daily limit.

If you are a heavy drinker and you take an NSAID, the risk of you having bleeding in your stomach may be higher. Speak to your GP or pharmacist if you are not sure whether you should be taking NSAIDs.

Food

There are no known interactions between NSAIDs and food. Ideally, take NSAIDs after eating and avoid taking them on an empty stomach. This will help minimise the risk of the medicine upsetting your stomach.

Other NSAIDs

It is always best to use one type of NSAID at a time to minimise the risks of side effects. If you have been prescribed a prescription-only NSAID, such as celecoxib, avoid taking any over-the-counter medication that contains ibuprofen or aspirin.

Many cold and flu remedies contain a combination of different medications, one of which is often an NSAID, such as ibuprofen.

So always carefully read the packet to check for possible interactions. Taking these sorts of remedies after already taking an NSAID could be potentially dangerous.+

Dosage 

Before prescribing a non-steroidal anti-inflammatory drug (NSAID), your GP will consider whether there is an alternative form of treatment that may be suitable. This will minimise your risk of having any side effects.

If your GP feels NSAIDs are the most appropriate form of treatment, they will prescribe the lowest effective dose for the shortest period of time necessary.

It is better to prescribe a low dose over a short period of time and, if necessary, to gradually increase it. By doing this, any side effects should not be as severe.

Effects of specific NSAIDs

Your tolerance to different types of NSAIDs can vary greatly, as can your pain relief. While one type of NSAID may cause no side effects and be very effective, another type may not be as effective, or it may have an adverse effect on your gastrointestinal tract, heart, circulation or kidneys.

Therefore, before prescribing a different type of NSAID, your GP will carefully consider your individual circumstances and your likelihood of having any sort of reaction to the medicine. Do not switch between NSAIDs unless your GP agrees that it is safe for you to do so.

Overdose

It is important to strictly follow all instructions about the recommended dosage for your particular NSAID. If you exceed the recommended dose, you risk experiencing adverse effects, which could be minor, moderate, or serious.

Minor effects of an overdose include:



upset stomach



skin irritation



drowsiness



tachycardia (rapid heartbeat)



Moderate effects of an overdose include brief seizures (fits), particularly with an NSAID called mefenamic acid.

If you think you or someone else is having mild or moderate effects of an NSAID overdose, contact your GP immediately for advice. If this is not possible

Serious effects of an overdose include:



prolonged and repeated seizures (fits)



serious breathing difficulties



loss of consciousness



A serious NSAID overdose is a medical emergency. If you think you or someone else is having serious effects of an NSAID overdose, call 999 immediately and ask for an ambulance.

Alternatives to NSAIDs 

If you have been advised not to take non-steroidal anti-inflammatory drugs (NSAIDs), a number of alternative treatments can be used.

Alternatives for some of the most common conditions treated with NSAIDs are listed below.

Pain

If you need medication to treat pain, paracetamol can be used in almost all cases. An exception to this would be in cases of severe liver disease where lower doses must be used because paracetamol in full doses can damage the liver.

You should seek advice from a pain specialist before taking painkillers other than NSAIDs, paracetamol or aspirin.

There are also a number of non-drug-based treatments for pain, such as:



physiotherapy



acupuncture



talking therapies, such as cognitive behavioural therapy, which are designed to help you cope better with pain



Gout

If you have gout, a medication called colchicine, or oral steroids are an effective alternative to using an NSAID.

Osteoarthritis

Alternative treatments for osteoarthritis include:



codeine – a mild opiate-based painkiller



capsaicin cream – which helps block the nerves from sending pain signals to the brain



corticosteroid injections – these help to reduce the symptoms of acute pain and swelling



surgery – such as a hip replacement or knee replacement



Rheumatoid arthritis

Alternative treatments for rheumatoid arthritis include:

 



codeine – a mild opiate-based painkiller



oral corticosteroids are occasionally used



corticosteroid injections – these help to reduce the symptoms of pain and swelling



disease-modifying anti-rheumatic drugs (DMARDs) – a type of medication that can help to ease symptoms and slow down the progression of rheumatoid arthritis



biological treatments – newer medications such as TNF-alpha inhibitors which work by stopping particular chemicals in the blood from activating your immune system