NSAID Side Effects

Welcome to this video on non-steroidal anti-inflammatory drugs and their effects. Nonsteroidal anti-inflammatory drugs are most often referred to as NSAIDs [enseds]. NSAIDs have anti-inflammatory effects that are similar to those of steroids but without some of the serious adverse effects.

Indications for NSAIDS include:

  • Mild to moderate pain
  • Fever
  • Various ophthalmic uses
  • Primary dysmenorrhea
  • Tendinitis and bursitis
  • Ankylosing spondylitis
  • Rheumatoid arthritis
  • Juvenile rheumatoid arthritis
  • Osteoarthritis
  • and Gout, specifically acute gouty arthritis

NSAIDs act by inhibiting the enzyme cyclooxygenase (COX). Cyclooxygenase enzymes include two isoenzymes:

  • Cyclooxygenase 1 (COX-1) and
  • Cyclooxygenase 2 (COX-2)

NSAIDs inhibit both COX-1 and COX-2 OR COX-2 alone.

Cyclooxygenase acts by converting arachidonic acid (which is released from phospholipids in cell membranes) to prostaglandins and related compounds, which are necessary to carry out many bodily processes.

COX-1 is found in tissues throughout the body where it has primarily beneficial functions, such as:

  • Protecting gastric mucosa
  • Supporting renal function
  • Promoting platelet aggregation AND
  • Promoting macrophage differentiation

Thus, inhibiting COX-1 does not relieve pain or inflammation.

COX-2, however, has primarily inflammatory functions.

COX-2 is active primarily at the site of injuries, where it mediates the inflammatory response, and in the brain, where it responds to injuries by:

  • Promoting vasodilation (in inflammation)
  • Sensitizing receptors to painful stimuli
  • Mediating the fever response AND
  • Mediating the perception of pain

Thus, inhibiting COX-2 relieves pain and inflammation.

However, in addition to the harmful processes, COX-2 also has some beneficial processes:

  • Promoting renal function and perfusion, and
  • Promoting vasodilation (preventing vasoconstriction)

Most first-generation NSAIDs are non-selective cyclooxygenase inhibitors, meaning that they inhibit both COX-1 and COX-2.

Some later generations are selective for COX-2 only.

The most commonly used NSAIDs are non-specific, especially the older drugs, such as:

  • Ibuprofen
  • Naproxen AND
  • Indomethacin

Specific COX-2 inhibitors include:

  • Celecoxib (Celebrex®)
  • Meloxicam AND
  • Diclofenac (a topical preparation)

Most NSAIDs are available by prescription, but some, such as ibuprofen and naproxen, are available in lesser doses over-the-counter.

So, what happens when COX-1 and COX-2 are inhibited?

Let’s look first at the effects of an NSAID on COX-1.

  • Instead of protecting the gastric mucosa, ulceration and bleeding occurs
  • Instead of supporting renal function, renal impairment occurs
  • Instead of promoting platelet aggregation, anti-platelet action occurs AND
  • Instead of promoting macrophage differentiation, macrophages develop a more inflammatory state

While most of the changes resulting from COX-1 inhibition are harmful, the anti-platelet action may be beneficial because it can reduce the risk of myocardial infarction and stroke.

This is the reason that aspirin (a first-generation NSAID) is usually avoided for control of pain and inflammation but used in low doses for its antiplatelet action.

Now, let’s take a look at the effects of an NSAID on COX-2:

  • Instead of promoting vasodilation, it causes vasoconstriction, which reduces swelling but also increases the risk of myocardial infarction and stroke
  • Instead of sensitizing receptors to painful stimuli and mediating the perception of pain, it reduces pain
  • Instead of promoting renal function and perfusion, it impairs renal function

Most of the adverse effects associated with NSAIDs result from COX-1 inhibition, especially their effects on the GI system. While most therapeutic effects result from COX-2 inhibition, selective COX-2 inhibitors also pose risks.

Some of the early COX-2 inhibitors, such as rofecoxib (Vioxx®) were taken off of the market because they doubled the risk of heart attack and stroke.

Adverse effects of NSAIDs may include:

  • Gas, stomach pain, nausea, vomiting, gastric ulcers, GI bleeding, hemorrhage, or diarrhea
  • Tinnitus and possible hearing loss
  • Headache and dizziness
  • Allergic reactions, sometimes as serious as anaphylaxis
  • Acute renal failure
  • Hepatic toxicity
  • Heart failure, myocardial infarction, or stroke AND
  • Altered hemostasis (that is associated with platelets)

A range of NSAIDs is now available in both nonspecific and COX-2-specific formulations. So, while one may be ineffective, another may be effective.

While aspirin is an NSAID, it differs from other NSAIDS in that its effects on COX-1 and COX-2 are irreversible. In other words, COX-1 and COX-2 remain inhibited until new COX-1 and COX-2 are synthesized.

The effects of other NSAIDs on COX-1 and COX-2 are reversible and decrease along with the blood titre.

Contraindications to the use of NSAIDs include:

  • Pregnancy at 20 weeks or later (risk of low amniotic fluid)
  • Breastfeeding
  • Anticoagulant therapy
  • Inflammatory bowel disease
  • Uncontrolled hypertension
  • Sensitivity to specific ingredients within the drug, and
  • The preoperative period: generally NSAIDs should be avoided for one week prior to surgery to reduce the risk of bleeding

Additional contraindications include:

  • A history of coronary artery bypass, transient ischemic attack, stroke, and heart disease
  • A history of cirrhotic liver disease, heart disease, and renal disease

NSAIDs are the most commonly prescribed medications for pain and inflammation, accounting for up to 10% of all prescriptions. However, every year thousands of people die from adverse effects, most often GI bleeding,

Because some NSAIDs are inexpensive and available over-the-counter, people often view them as safer than they actually are.

It’s critical to stress the importance of following directions and limiting use to no more than 3 days for fever or 10 days for pain unless monitored by a physician.

Thanks for watching and happy studying!

 

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by Mometrix Test Preparation | This Page Last Updated: February 25, 2022