Dangers of Nonsteroidal Anti-inflammatory Drugs (NSAIDs)| PatientsEngage

Submitted by PatientsEngage on 12 August 2024

Stock pic of capsules with overlay of blue strip with text Risks of NSAIDs

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are the drug of choice for alleviating pain. However it is important to understand the effects of them on various organs and use them with care.

In ancient times, herbs and plants were used to treat pain, fever, sores, swelling and inflammation. In 1879, aspirin was discovered and to this date continues to be widely used by people to deal with pain and inflammation. Aspirin belongs to a class of drugs called NSAIDs which are known for their anti-inflammatory, pain and fever reducing properties. However, with the benefits, followed the harms of NSAID use, especially since the side-effects went undetected for decades and NSAID use became common due to easy availability and cheap pricing.

For minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions, most people often go to a drug store/chemist/ pharmacy instead of a doctor’s clinic for relief. Over-the-Counter (OTC) Medicines are drugs which are legally allowed to be sold by shops without need for a prescription. Technically, all drugs are Over-the-Counter unless they are specifically stated as Prescription only drugs. Over-the-Counter drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns.

What are Nonsteroidal anti-inflammatory drugs (NSAIDs)?

They are part of a therapeutic drug class, which are used in the treatment of acute or chronic pain, inflammation and fever caused by various conditions. The most prominent NSAIDs are aspirin, ibuprofen and naproxen, diclofenac, ketoprofen; all available Over-The-Counter (OTC) in most countries.

The subtle difference between NSAIDs, Analgesics, and Anti Inflammatory medicines

Analgesics, or painkillers, are a class of drugs that provide relief from various kind of pain ranging from headaches, body ache, injury pain or joint pain. Anti-inflammatory class of medication, as the name indicates, works against any inflammation caused by injury or arthritis, while opioid analgesics work on the perception of pain by the brain and hence reduce the feeling of pain.

The greatest difference is that analgesics work by cutting off pain signals before they reach the brain and thereby the perception of the amount of pain you’re feeling. NSAIDs have a dual effect of reducing inflammation, by preventing the body from producing certain chemicals that cause inflammation and thereby providing relief from pain.

However, both these do not work on what is actually causing the pain and therefore may not provide relief, especially if this is connected to chronic pain/ inflammation.

Magnitude of NSAID use:

Worldwide, approximately 30 million people take NSAIDs daily. The data of global and Indian studies showed that the total number of NSAIDs prescription ranges from 15% to 40% of the total drugs prescribed in a random number of prescriptions (~300-1000) selected for the multiple studies.

There are approximately two dozen different Over-the-Counter and prescription NSAIDs available globally.

In India they are prescription medicine in some states (due to over or misuse during Dengue/Chikungunya outbreak), but are largely available Over-the-Counter and hence widely used/misused/overused for symptoms.

The problem with Nonsteroidal anti-inflammatory Drugs

NSAIDs accounted for 29% of the Adverse Drug Reaction cases, leading to hospital admission in the US.⁵ In UK, NSAIDs are responsible for 30% of hospital admissions for Adverse Drug Reactions such as bleeding, heart attack, stroke, and kidney damage.

The use of NSAIDs is generally high among the patient population in India. Although several other classes of analgesics are available, most patients are either prescribed NSAIDs or consume NSAIDs without the consent of their physician (Over-the-Counter route).

Although NSAIDs are effective, widespread use presents risks that can increase with long-term use and higher doses. The adverse events observed included Gastro-intestinal (GI) bleeds, peptic ulceration in the lining of the digestive tract, bleeding in the brain, and kidney function impairment. Dangerous drug interactions with NSAIDs may occur when used in combination with anticoagulants (drugs that prevent blood from clotting), diuretics, antihypertensives, and hypoglycemic (antidiabetic) drugs.

In India, the result of an interim analysis of a study indicates prevalence of Gastro-intestinal (30.08%), cardiac (42.77%) and kidney related complications (27.88%) with the use of NSAIDs and also a trend of NSAIDs being used in such patients.

Side-effects of NSAID use on various organs and body systems:

Cardiovascular
The risk of major vascular events related to blood vessels in the body affecting heart function was increased by 33% in patients taking a diclofenac. Other side effects include myocardial infarction (heart attack), thromboembolic events involving blood clots, and atrial fibrillation.

Gastro-intestinal
The use of NSAIDs increases the risk of Gastro-intestinal toxicity, such as the development of peptic ulcer disease (PUD), upper gastro-intestinal haemorrhage/ bleeding, or perforation. The risk of complications may vary among NSAIDs. About 25% of patients who use NSAIDs chronically will develop PUD.

However, if anti-inflammatory treatment is absolutely necessary, other class of drugs like a proton pump inhibitor (PPI) or misoprostol are recommended by the doctor.

Kidney
Chronic NSAID use can lead to severe kidney impairment due to its direct and indirect effects on the kidney. The use of NSAIDs can increase blood pressure (thus making antihypertensive drugs less effective), cause fluid retention, and decrease perfusion in the kidney, changes in blood flow and thereby decrease kidney function in patients with kidney disease. Other agents such as acetaminophen, tramadol, or opioids used short-term may be safer alternatives and as effective as NSAIDs in the management of pain.

Side-effects are more prominent in people with existing kidney dysfunction. Complications that can occur include acute kidney dysfunction, fluid and electrolyte disorders, papillary necrosis in the kidney, and nephrotic syndrome/ interstitial nephritis.

Patients with high Blood Pressure or Chronic Kidney Disease, should have their serum creatinine and potassium checked routinely if they are on NSAIDS. Physicians may not be aware that patients are using Over-the-Counter NSAIDs; therefore, they may not be monitoring patients routinely for these parameters.

Liver
About 10% of total drug-induced hepatotoxicity or liver damage is NSAID-related⁹and this is categorised as drug induced liver damage, presenting as hepatitis 1-3 months later. Hepatocellular injury – damage to liver cells can occur. Severity can range from asymptomatic elevated enzyme levels in the liver, to hepatitis with jaundice, severe liver failure which can be fatal. Symptoms can include fever, malaise, fatigue, jaundice and itching.

Guidelines for NSAIDs prescription and use

In India NSAIDs were made prescription in certain states due to their misuse or overuse. In July 2023, the Drug Controller Authority of Delhi had banned the Over-the-Counter sale of pain killers, due to rising cases of Dengue, Chikungunya as these drugs reduce the production of blood platelets.

Chemists have been asked not to sell medicines from Aspirin, Ibuprofen & Diclofenac groups over the counter. The authority has also warned of stringent action if any retail chemist is found violating the instructions.

The regulatory body said the drugs could be sold only after a prescription from a doctor and asked the chemists to maintain records of stocks of such painkillers.

What a patient must know about NSAIDs

NSAIDs, both prescription and Over-the-Counter, are widely used by a variety of patient populations. Patients should check with the doctor before purchasing Over-the-Counter products, especially combination products that may contain NSAIDs. They should not therefore buy any prescription NSAIDs on their own.

Special care needs to be exercised with ageing population who may have several co-morbidities and instances of multiple prescriptions. The overall drug absorption and elimination profile could be compromised in elderly due to impaired liver or kidney function and thereby affect the way the medicine works in their body. Drug clearance also could be affected due to metabolic changes due to ageing.

Always check with the doctor when you are adding on NSAIDs to your daily meds to prevent any drug-to-drug interactions. NSAIDs may interact with other medicines to cause unwanted effects:

List of Drugs that interact with NSAIDs	Unwanted Side effects
Blood thinning medications such as warfarin	Risk of bleeding
Medicines for heart failure and high blood pressure including ACE inhibitors, beta blockers and diuretics	Kidney failure. Opposes effects and stops them from working effectively
Low-dose aspirin or corticosteroid medicine like prednisolone	Increases risk of gastrointestinal ulceration or bleeding

Alcohol (regular or heavy drinking) also interacts with NSAIDs and increases risk of gastrointestinal damage or bleeding
Do not increase the dose or frequency without checking with your doctor first.
Be extra cautious when you have any chronic conditions that impact your cardiovascular, gastrointestinal, kidney and liver systems.
Always take NSAIDS with or after food. This will reduce risks of peptic or digestive tract ulcers.
Try other non-pharmacological remedies for pain such as hot/cold compresses, massages, rest etc.

Additionally, be patient and let the medication do its job
It is important to be aware that all medicines follow a cycle of ADME in the body after intake to have its best effect and not be toxic. ADME is an acronym that stands for Absorption (how the drug enters the body), Distribution (via the blood stream and to the organs), Metabolism (breakdown into useful parts) and Excretion (removal of unnecessary part of the medication).
At no point should the body have more than the required dose of a medication in the blood stream or at the site of where it needs to act.
Hence, it is imperative that we remember the following when using any drug:

The importance of timely administration of medication. Always take your medicines at the right interval as suggested by the doctor.
Wait for the medicine it to start its effect. Be patient. Do not take multiple doses or other similar medicines to improve its efficacy. For example, people often want painkillers to start working immediately. If it does not work within 10-15 minutes, they take more of the same other types of painkillers.
Irrationally combining medications can lead to an overdose of one of the medicines in a combined dose or it’s metabolite or unwanted part, in the blood stream which can then prove to be toxic and fatal.

Role of the Health Care Professional (HCP)

Consulting doctors are in a unique position to both identify and prevent adverse events associated with NSAID use.

Every patient using either OTC or prescription NSAIDs should be screened for all of the potential risks previously mentioned. If patients are taking NSAIDs, they should get their creatinine and potassium levels checked regularly.
NSAIDs should be avoided in patients with a high risk for both Cardiovascular and Gastrointestinal events.
Avoid NSAIDs altogether in persons with Diabetes or substitute with Paracetamol provided liver functions are normal.
Patients should be educated that NSAIDs must be used at the lowest possible dose for the shortest duration possible to avoid adverse effects.
Encourage patients to have a comprehensive medication card whenever starting a new prescription or OTC drug, so careful monitoring can take place for drug-drug and drug-disease interactions.
Open communication between patients, doctors/prescribers, and pharmacists is key for prevention and early detection of NSAID-associated adverse events.

In conclusion, as much as Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are the drug of choice for alleviating pain, it is important to use them with caution and only after consultation with your doctor.

Take extra care when using it in combination with any other drugs.
Ask your doctor to prescribe a less harmful alternative based on your need.
Follow the correct dosage and avoid prolonged use, except if needed post medical consultation.
Use a prescription vs buying these over the counter.

Written by Lata Chopra (background in pharmacy) and Dr. Shital Raval Patel

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