Using Anti-inflammatory Analgesics Safely: How to Consider the Gastric, Renal, and Cardiovascular Risks of NSAIDs

Headaches, toothaches, menstrual pain, lower back pain, shoulder pain, muscle pain, and joint pain. When faced with these common pains, many people first think of painkillers available at a pharmacy. Because they are easily accessible as over-the-counter drugs and their effects are well-understood, anti-inflammatory analgesics are often found in home medicine cabinets.

Among these, loxoprofen, ibuprofen, diclofenac, naproxen, and celecoxib are non-steroidal anti-inflammatory drugs, or NSAIDs. They have the effect of relieving pain, suppressing inflammation, and reducing fever, and are used in a wide range of settings, including orthopedics, dentistry, gynecology, internal medicine, and emergency departments.

NSAIDs are not bad drugs. In fact, for many patients, they are essential medications for reducing pain, allowing them to sleep, enabling them to walk, and maintaining their daily lives. The problem is that because their effects are clear and they are easy to obtain, their risks are often underestimated.

What is medically important is not to be vaguely afraid that "anti-inflammatory analgesics are bad for the body." It is to know which organs are affected, under what conditions, and to what extent risks are likely to occur. With NSAIDs, one should be particularly careful about the stomach and intestines, kidneys, cardiovascular system, and interactions with other drugs. Even with the same pill, the meaning changes significantly between a young, healthy person using it for a short period and an elderly person with reduced kidney function who is taking anticoagulants.

Why do NSAIDs work?

The main action of NSAIDs is to suppress an enzyme called cyclooxygenase, or COX for short. COX is involved in the production of substances called prostaglandins. Since prostaglandins are related to pain, inflammation, and fever, suppressing this pathway can alleviate pain and inflammation.

However, prostaglandins are not only involved in pain and inflammation. They also have necessary roles in the body, such as protecting the gastric mucosa, maintaining blood flow to the kidneys, and affecting the function of platelets and blood vessels. Therefore, when prostaglandins are suppressed by NSAIDs, while pain is alleviated, effects can occur in the stomach, kidneys, and blood vessels.

This is an important point in understanding NSAIDs. NSAIDs are not just "strong painkillers." They are drugs that act on the pathway of inflammation and prostaglandins. The reason they work and their side effects are within the same mechanism.

It is not just stomach pain; ulcers and bleeding are the issues

The most well-known side effect of NSAIDs is their effect on the stomach. Many people experience a heavy stomach, nausea, stomach pain, loss of appetite, or heartburn after taking them.

However, what is more clinically problematic is not just gastritis, but gastric ulcers, duodenal ulcers, gastrointestinal bleeding, and, rarely, perforation. Because NSAIDs reduce the prostaglandins that protect the gastric mucosa, they make it more susceptible to damage from stomach acid and digestive juices.

What one should be careful about is that safety cannot be judged by the intensity of stomach pain alone. Ulcers and bleeding can occur even without severe stomach pain. Conversely, even if there is strong stomach discomfort, it does not necessarily mean there is a serious ulcer. Symptoms and actual risk do not perfectly align.

Black stools, vomiting blood, vomiting that looks like coffee grounds, severe lightheadedness, palpitations, shortness of breath, pale complexion, and sudden anemia are symptoms that suggest gastrointestinal bleeding. Especially for the elderly, people with heart disease, and those using anticoagulants or antiplatelet drugs, even a single instance of bleeding can be a major burden.

Aspirin needs to be considered a little differently

Aspirin is also included in NSAIDs in a broad sense. However, low-dose aspirin is sometimes used not for general pain relief, but to suppress platelet function and prevent the recurrence of myocardial infarction or cerebral infarction. Therefore, its clinical positioning is slightly different from general anti-inflammatory analgesics like loxoprofen or ibuprofen.

However, even low-dose aspirin carries a risk of gastrointestinal bleeding. Furthermore, using it together with other NSAIDs, anticoagulants, antiplatelet drugs, corticosteroids, or selective serotonin reuptake inhibitors can increase the risk of bleeding.

It is not necessarily "safe because it is a small dose." Aspirin is a very important drug for those who need it, but it is safer to check with a pharmacist or doctor when adding other painkillers.

Effects on the kidneys are easily overlooked

What is easily overlooked with NSAIDs is their effect on the kidneys. In the kidneys, prostaglandins have the role of maintaining blood flow. For people who are healthy, not dehydrated, and have normal kidney function, short-term use of NSAIDs often does not cause major problems. However, in people whose kidneys are already weak or who are in a state of dehydration, NSAIDs can reduce blood flow to the kidneys and cause acute kidney injury.

One should be particularly careful when there is diarrhea, vomiting, fever, loss of appetite, dehydration due to heat, heart failure, cirrhosis, or chronic kidney disease. In such conditions, the kidneys are more sensitive than usual to maintain blood flow. Using NSAIDs during those times can cause kidney function to deteriorate suddenly.

Also, caution is required when combining them with antihypertensive drugs or diuretics. It is known that the combination of diuretics, ACE inhibitors or ARBs, and NSAIDs increases the risk of acute kidney injury. This is the combination known as the "triple whammy." If someone taking blood pressure medication adds over-the-counter NSAIDs for lower back pain or joint pain, they need to be more cautious than they might think.

There are also risks to the heart and blood vessels

NSAIDs can also affect the cardiovascular system. Issues include increased blood pressure, swelling, worsening heart failure, and a potential slight increase in the risk of myocardial infarction and stroke.

This risk varies depending on the type of drug, the dosage, the duration of use, and the individual's cardiovascular risk. People who already have a history of myocardial infarction or stroke, have heart failure, have unstable blood pressure, or have conditions such as diabetes, chronic kidney disease, smoking, or high LDL cholesterol should not use NSAIDs casually as ordinary painkillers.

Selective COX-2 inhibitors are sometimes used to reduce gastrointestinal disorders, but an assessment of cardiovascular risk is necessary. Just because a drug may be gentler on the stomach does not mean it is safe for everyone.

Medically, rather than asking "which NSAID is the strongest," it is necessary to consider "for this person, which drug, at what dose, and for what duration is acceptable."

Who needs to be especially careful?

While NSAIDs are useful for many people when used for a short period, some people are at higher risk. Especially in the following cases, it is safer to consult a doctor or pharmacist rather than using them for a long time based on your own judgment.

• You are 65 years of age or older.

• You have a history of gastric ulcer, duodenal ulcer, black stools, hematemesis, or gastrointestinal bleeding.

• You have chronic kidney disease, reduced renal function, diabetes, heart failure, or cirrhosis.

• You have a history of myocardial infarction, angina pectoris, cerebral infarction, cerebral hemorrhage, or peripheral artery disease.

• Your blood pressure control is unstable.

• You are taking anticoagulants, antiplatelet drugs, corticosteroids, diuretics, ACE inhibitors, or ARBs.

• You are using multiple painkillers or over-the-counter drugs at the same time.

• You have been taking painkillers for a long time for joint pain or lower back pain.

Just because you fall into these categories does not mean you absolutely cannot use NSAIDs. However, it will be necessary to consider the choice of drug, dosage, duration, concomitant use of stomach medicine, confirmation of renal function, and alternative treatments.

PPIs protect the stomach, but they are not a panacea

For people at high risk of gastric ulcers or upper gastrointestinal bleeding, doctors may prescribe PPIs, or proton pump inhibitors, in combination. Omeprazole, esomeprazole, lansoprazole, rabeprazole, and vonoprazan are used in this area.

PPIs strongly suppress stomach acid and can be useful in preventing NSAID-related gastric and duodenal ulcers. This can be particularly important for people with a history of ulcers, the elderly, and those taking low-dose aspirin or anticoagulants concurrently.

However, taking a PPI does not make NSAIDs completely safe. PPIs are drugs that primarily reduce upper gastrointestinal risks associated with stomach acid. They are not drugs that prevent renal impairment, blood pressure elevation, worsening of heart failure, or cardiovascular risks caused by NSAIDs. Furthermore, they cannot completely prevent damage to the small or large intestine.

The understanding that it is safe because you are taking stomach medicine along with it is dangerous. While protecting the stomach is important, the risks of NSAIDs are not limited to the stomach.

Helicobacter pylori and NSAIDs

Helicobacter pylori is also related to gastric and duodenal ulcers. Both NSAIDs and H. pylori are involved in ulcer risk. When both overlap, the risk of ulcers and bleeding may increase further.

For people who have had ulcers or gastrointestinal bleeding in the past, or who need to use NSAIDs or low-dose aspirin for a long period, testing for and eradicating H. pylori may be considered. However, eradication does not eliminate all risks. In high-risk individuals, stomach protection such as PPIs may still be necessary even after eradication.

Conversely, not all stomach pain is caused by H. pylori. If you have persistent stomach pain, black stools, anemia, weight loss, loss of appetite, or nausea, it is important to be evaluated at a medical institution rather than continuing to suppress it with over-the-counter drugs.

Acetaminophen is different from NSAIDs

When considering painkillers, acetaminophen is also frequently used. In Japan, it is prescribed under names like Calonal and can also be included in over-the-counter drugs. Acetaminophen is an antipyretic analgesic, but unlike NSAIDs, it does not have the same strong anti-inflammatory effect.

In general, acetaminophen is considered to have less impact on gastric ulcers and renal blood flow compared to NSAIDs. Therefore, it may be an option for people with a high risk of gastrointestinal bleeding or renal risk. However, overdose can cause severe liver damage, and it is by no means an infinitely safe drug.

Over-the-counter cold medicines and analgesics may contain overlapping amounts of acetaminophen. If you use multiple drugs at the same time, the total amount may increase without the person realizing it. It is important to check not only the name of the drug but also the ingredients.

Common pitfalls with over-the-counter drugs

The convenience of over-the-counter drugs is a major advantage. For mild headaches, menstrual pain, or short-term muscle pain, using them according to the dosage and administration can be helpful. However, just because they are over-the-counter does not mean they are safe.

A common pitfall is overlapping the same type of NSAIDs. For example, taking another brand-name NSAID while already taking loxoprofen. Taking over-the-counter painkillers even though NSAIDs have been prescribed. Not realizing that a cold medicine contains antipyretic analgesic ingredients. Such duplication increases the risk of side effects.

Another problem is continuing to take them without looking at the cause of the pain. If back pain, joint pain, headaches, abdominal pain, or toothaches persist, simply suppressing the pain is not enough. Inflammation, infection, fractures, nerve damage, tumors, vascular diseases, and visceral diseases may be hidden.

Feeling temporarily better with painkillers is not the same as the disease being cured. For pain that lasts more than a few days, worsening pain, recurring pain, or pain accompanied by fever, numbness, paralysis, or weight loss, evaluation at a medical institution is necessary.

Practical considerations when taking medication

The principle when using NSAIDs is to use them when necessary, in the minimum amount, and for the shortest period. Use them for a short time when the pain is severe, and then check if you can stop. They are not drugs to be taken aimlessly every day.

When taking them, being aware of a few points will increase safety. These include avoiding taking them on an empty stomach, following the dosage and administration, not overlapping the same NSAIDs, consulting a doctor if continuing for a long period, and consulting a pharmacist with your medication notebook if you have chronic illnesses or are taking other medications.

Also, depending on the type of pain, methods other than oral NSAIDs may be suitable. For localized pain, options include topical NSAIDs, compresses, physical therapy, exercise therapy, weight management, heat or cold therapy, joint injections, and disease-specific treatments. For chronic pain, it is necessary to consider not only medication but also sleep, psychological factors, muscle strength, posture, and work environment.

NSAIDs are a useful tool, but they are not the only tool. It is necessary to think of suppressing pain and treating the background of the pain as separate things.

Symptoms that warrant medical attention

If you experience any of the following symptoms while taking NSAIDs, please consult a medical institution as soon as possible.

• Black stools, bloody stools, vomiting blood, or vomiting material that looks like coffee grounds.

• Severe stomach pain, persistent upper abdominal pain, cold sweats, or lightheadedness.

• Pale complexion, heart palpitations, shortness of breath, or severe fatigue.

• A noticeable decrease in urine output, significant swelling, or sudden weight gain.

• Chest pain, difficulty breathing, weakness in one side of the body, or slurred speech.

• Difficulty breathing, swelling of the face or lips, or generalized hives after taking the medication.

• Pain does not improve, and you feel the urge to increase the dosage or frequency of the medication.

These may be different from general stomach upset or mild side effects. In the elderly, in particular, symptoms may not be clearly apparent. Changes such as sudden loss of energy, decreased appetite, feeling unfocused, or low urine output are also important.

Avoid self-judgment during pregnancy and breastfeeding

When choosing analgesics during pregnancy, the points of caution change depending on the stage. NSAIDs may affect fetal circulation and amniotic fluid volume in the third trimester and, in principle, should not be used based on self-judgment. If you are pregnant or think you might be, it is necessary to consult a doctor or pharmacist.

Even while breastfeeding, decisions vary depending on the type and amount of medication and the baby's condition. Even when using over-the-counter drugs for a short period, it is safer not to combine multiple medications based on self-judgment. If you are pregnant, breastfeeding, have underlying conditions, or are taking other medications, it is important to get into the habit of checking rather than assuming that "it's fine because I always use this medicine."

Summary: Balancing pain relief with safe usage

NSAIDs are medications that alleviate pain for many people and support their daily lives. They are useful in many situations, such as headaches, menstrual pain, toothaches, acute muscle pain, joint pain, and inflammatory pain. When used appropriately, they can support sleep, activity, work, and daily life.

However, NSAIDs are not just "effective over-the-counter drugs." Gastric ulcers, gastrointestinal bleeding, renal dysfunction, elevated blood pressure, worsening heart failure, cardiovascular risk, and drug interactions can become issues. Especially for the elderly, those with a history of gastric ulcers, kidney disease, cardiovascular disease, or those currently using anticoagulants or antiplatelet drugs, the risk of even a single tablet can change.

The important thing is not to be afraid and endure necessary pain relief. It is about alleviating pain without placing unnecessary burdens on the stomach, kidneys, and cardiovascular system. To achieve this, it is important to use the minimum effective dose for the shortest possible duration, avoid overlapping medications, check for underlying conditions and other drugs, and investigate the cause of prolonged pain.

Painkillers are tools for protecting your life. However, tools can be both a help and a burden depending on how they are used. To use NSAIDs safely, it is necessary to have a perspective that looks not only at the pain but also at the individual's age, organ function, medications, and medical history.