Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Pain Management

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Pain Management

(Dr. Guru Prasad Mohanta, Professor, Department of Pharmacy, Annamalai University, Annamalai Nagar – 608 002, Tamil Nadu, E. mail: gpmohanta@hotmail.com)

The introduction of some COX – 2 (cyclooxygenase isozymes) inhibitors and their subsequent withdrawal from the market brought serious concern on use of pain relieving medicines. The COX – 2 inhibitors like valdecoxib and rofecoxib were instant hits in pain management as they appeared to cause fewer episodes of serious gastro-intestinal toxicity compared to other available Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Sooner they were found to be more damaging than the other NSAIDs and they were banned or withdrawn from use due to increased cardiac events. Many litigations followed and the pharmaceutical companies were accused of withholding the cardiovascular events data reported during clinical trials. 

The NSAIDs are an important group of pain relieving medicines and have been in use for a variety of pain condition though they differ in their effectiveness. They have significant use in patients with arthritis, low-back pain and soft tissue pain. They do differ in their side effects too. Gastrointestinal bleeding and perforations are common and serious adverse events. These serious events lead to hospitalization and even deaths. The factors known to be responsible for this adverse effect are: types and dose of the drug, use of combination, use of other drugs – anticoagulants, steroids, smoking, alcohol use, older age and patient’s susceptibility. Patients with history of ulcer are at more risk. The risk of toxicity increases with increasing dose and length of treatment. Aspirin, the common NSAID, is usually available as plain aspirin, enteric coated aspirin and effervescent aspirin. Though initially it was believed that enteric coated form has less risk than the other two forms, the new evidence suggests that all three forms have equal risk in producing gastric bleeding.

The patients need to be made aware of the risk involved; to stop the use of medicine and report back immediately. Some of the warning signs are: severe abdominal and stomach pain, cramping or burning; severe and continuing nausea, heart burn, indigestion; blood or black, tarry stools; vomiting blood or material that looks like coffee grounds; and spitting blood. This would help preventing major harm to patients. 

The recent study reports give a new warning. The use of NSAIDs except naproxen is associated with increased risk of cardiovascular death, fatal and non-fatal myocardial infarction and stroke. The mechanism of this risk factor is related to their effect on COX – 1 and Cox – 2 inhibitors. Diclofenac is found to be completely inhibiting COX – 2 and partially COX – 1 and has the maximum risk of cardiovascular events. On the other hand, naproxen inhibits both COX 1 and COX 2 and has the least cardio vascular risk. The NSAIDs that inhibit COX-2 without complete inhibition of COX-1 has the greatest risk.

All the NSAIDs have almost similar effectiveness. While it is important to make a balance on efficacy and safety in use of medicine, the following few tips would help minimising the harm but providing maximum benefits in pain management: 

·         Use at the lowest effective dose for the lowest possible time;

·         Identify the NSAID with lowest risk profile;

·         Exercise caution while selecting diclofenac as it has maximum cardiovascular risk;

·         Consider the risk of gastrointestinal bleeding and cardiovascular events before recommending or using.