NSAID

Products

Nonsteroidal anti-inflammatory drugs (NSAIDs) are available in numerous dosage forms. These include film-coated tablets, tablets, sustained-release tablets, oral suspensions, oral granules, suppositories, NSAID eye drops, lozenges, emulsifying gels, and creams (selection). The first active ingredient from this group was salicylic acid, which was used medicinally in the 19th century in the form of the sodium salt sodium salicylate. However, it irritated the digestive tract too much and therefore did not catch on. Much more successful was the acetylated derivative, acetylsalicylic acid (aspirin), which was launched by Bayer shortly before the turn of the millennium in 1899 and is still one of the most important NSAIDs today. Numerous new NSAIDs were developed in the 20th century. Among the best known are, for example, diclofenac, ibuprofen, and naproxen, with the addition of mefenamic acid in many countries (see below).

Structure and properties

NSAIDs are classified according to their chemical structure. The groups include the anthranilic acid derivatives (e.g., mefenamic acid), the (aryl)acetic acid derivatives (e.g., diclofenac), the oxicams (e.g., piroxicam), the propionic acid derivatives (e.g., ibuprofen), and the salicylates (e.g., acetylsalicylic acid). NSAIDs are also called “acid analgesics” because many representatives are organic acids and typically contain a carboxy group (-COOH). The name nonsteroidal is used to distinguish NSAIDs from glucocorticoids, which are steroids.

Effects

Nonsteroidal anti-inflammatory drugs (ATC M01A) are:

  • Analgesic (pain-relieving)
  • Antipyretic (antipyretic)
  • Anti-inflammatory (antiphlogistic)
  • Platelet aggregation inhibitory (eg, acetylsalicylic acid).
  • Antitumoral

The effects are based on the inhibition of cyclooxygenases and thus the inhibition of the biosynthesis of prostaglandins and thromboxanes. COX-2 inhibitors are selective for cyclooxygenase-2 (COX-2).

Indications

Indications for the use of NSAIDs include:

Dosage

According to the SmPC. Many NSAIDs have a short half-life and therefore usually need to be taken up to about three times daily. For example, diclofenac has a half-life between 1 to 3 hours. Long-acting agents have also been developed, notably the oxicams and naproxen. NSAIDs are often prescribed along with something called gastric protection, usually a proton pump inhibitor (PPI), to reduce the risk of developing gastric and intestinal ulcers.

Abuse

Unlike other pain medications such as opioids, NSAIDs are not psychotropic and are not abused as intoxicants. However, overuse contrary to scientific recommendations is possible.

Active Ingredients

Known drugs or original drugs are listed in parentheses. Generic versions of many NSAIDs are also on the market. Other active ingredients exist that are not or no longer commercially available in many countries. Anthranilic acid derivatives (fenamates):

  • Etofenamate (Rheumon, Traumalix).
  • Flufenamic acid (Assan)
  • Meclofenamic acid (Meclomen, out of trade).
  • Mefenamic acid (Ponstan)
  • Niflumic acid

COX-2 inhibitor:

Acetic acid derivatives and arylacetic acid derivatives:

  • Aceclofenac (Beofenac, D).
  • Acemetacin (Tilur)
  • Bufexamac (Parfenac, out of commerce).
  • Diclofenac, Diclofenac gel (Voltaren).
  • Etodolac (Lodine)
  • Indometacin (Indocid)
  • Ketorolac (Acular)

NSAID eye drops:

  • Bromfenac (Yellox)
  • Diclofenac eye drops (Voltaren Ophtha).
  • Indometacin eye drops (Indophtal)
  • Ketorolac (Acular)
  • Nepafenac (Nevanac)

Oxicame:

  • Lornoxicam (Xefo, out of commerce).
  • Meloxicam (Mobicox, off the shelf)
  • Piroxicam (Felden), piroxicam gel
  • Tenoxicam (Tilcotil)

Propionic acid derivatives:

  • Benoxaprofen (out of commerce)
  • Dexibuprofen (Seractil)
  • Dexketoprofen (Ketesse)
  • Fenoprofen (not commercially available in many countries).
  • Flurbiprofen (Froben)
  • Flurbiprofen lozenges (Strepsils Dolo).
  • Ibuprofen (Brufen), ibuprofen lysinate, ibuprofen alginate, ibuprofen sodium.
  • Ketoprofen (Fastum)
  • Naproxen (Aleve)
  • Tiaprofenic acid (Surgam, D)

Salicylates:

  • Acetylsalicylic acid (aspirin).
  • Calcium carbasalate (Alcacyl tablets, Alca C).
  • Lysine acetyl salicylate (Alcacyl powder, Aspégic)
  • Salicylic acid (various)

Sulfonanilides:

  • Nimesulide (Aulin)

Contraindications

When using NSAIDs, numerous contraindications and precautions must be observed. Full details can be found in the drug label.

Interactions

NSAIDs can interact with numerous pharmaceutical agents. These include, for example, glucocorticoids, antihypertensives, anticoagulants, SSRIs, antidiabetics, lithium, probenecid, ciclosporin, tacrolimus, and methotrexate (selection). Alcohol may increase adverse effects. NSAIDs are often organic anions and may be substrates of CYP450 isozymes.

Adverse effects

The most common potential adverse effects include:

  • Gastrointestinal disturbances: Indigestion, diarrhea, nausea, vomiting, loss of appetite, constipation, abdominal pain, flatulence, tarry stools, vomiting of blood, and bleeding in the digestive tract
  • Central nervous and psychiatric side effects: Limitation of reaction, headache, dizziness, lightheadedness, fatigue, mood changes.
  • Fluid retention, water retention.
  • Skin rashes

The side effects occur mainly because the prostaglandins also perform physiological functions. Inhibition of their synthesis also suppresses their desirable effects. NSAIDs can cause serious to life-threatening side effects, especially with long-term therapy. These include gastric and intestinal ulcers, bleeding, perforations, cardiovascular diseases such as high blood pressure and a heart attack and stroke, liver disease, hepatitis, life-threatening skin reactions, anaphylaxis, blood count changes (agranulocytosis) and kidney dysfunction up to and including kidney failure.