Question

Compare between selective and non- selective NSAIDs as regards to their mechanism of action, pharmacological actions, side effects, clinical uses, and drug interactions. Give examples of drugs from each class, mention generic names as well as trade names

Answer 1

# Selective NSAIDs inhibit only the COX-2 enzyme, allowing for the production of the prostaglandins that protect the stomach, while still relieving fever, pain and inflammation. They do no have the anti-platelet effects associated with nonselective NSAIDs and so do not alter clotting.

# The Nonsteroidal anti-inflammatory drugs (NSAIDs) are members of a drug class that reduces pain, decreases fever, prevents blood clots, and in higher doses, decreases inflammation.

Side effects are depend on the specific drug but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease

# NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (COX-1 or COX-2). In the cells, these enzymes are involved in the synthesis of key biological mediators, namely prostaglandins, which are involved in inflammation, and thromboxanes, which are involved in blood clotting.

There are mainly two types of NSAIDs available: non-selective and COX-2 selective.Most NSAIDs are non-selective and inhibit the activity of both COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet aggregation and increase the risk of gastrointestinal ulcer COX-2 selective inhibitors have less gastrointestinal side effects but promote thrombosis and substantially increase the risk of heart attack.

COX-2 selective inhibitors are generally contraindicated due to the high risk of undiagnosed vascular disease.[These differential effects are due to the different roles and tissue localisations of each COX isoenzyme. By inhibiting physiological COX activity, all NSAIDs increase the risk of kidney disease and through a related mechanism, heart attack. In addition, NSAIDS can blunt the production of erythropoietin resulting in anaemia, since haemoglobin needs this hormone to be produced.

# Prolonged use is dangerous and case studies have shown the health risk with celecoxib

# Most NSAIDs act as nonselective inhibitors of the cyclooxygenase (COX) enzymes, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible as opposed to the mechanism of aspirin, which is irreversible inhibition.

COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated .

Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3–5. They are absorbed well from the stomach and intestinal mucosa. They are highly protein-bound in plasma .,usually to albumin, so that their volume of distribution typically approximates to plasma volume. Most NSAIDs are metabolized in the liver by oxidation and conjugation to inactive metabolites that typically are excreted in the urine, though some drugs are partially excreted in bile. Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.

# Ibuprofen and diclofenac have short half-lives (2–3 hours). Some NSAIDs (typically oxicams) have very long half-lives

NSAIDs may be used with caution by people with the following conditions:

Irritable bowel syndrome

Persons who are over age 50, and who have a family history of GI problem

Persons who have had past GI problems from NSAID use

NSAIDs should usually be avoided by people with the following conditions are as-

Peptic ulcer or stomach bleeding

Uncontrolled hypertension

Kidney disease

People that suffer with inflammatory bowel disease (Crohn's disease or ulcerative colitis)

NSAIDs are generally used for the symptomatic relief of the following conditions- examples are as

Osteoarthritis

Rheumatoid arthritis

Mild-to-moderate pain due to inflammation and tissue injury

Low back pain

Inflammatory arthropats (e.g., ankylosing spondylitis, psoriatic arthritis, reactive arthritis)

Tennis elbow

Headache

Migraine

Acute gout

Examples of non-selective NSAIDS include:

Aspirin

Diclofenac

Ibuprofen

Naproxen

Mefenamic acid

Indomethacin

Ketoprofen

Piroxicam

##££ Classification of NSAIDs are as follows-

Acetates: diclofenac, indomethacin, sulindac.

Fenamates: mefenamic acid.

Oxicams: piroxicam.

Propionates: ibuprofen, ketoprofen, naproxen.

Pyrazolones: phenylbutazone.

Salicylates: aspirin, diflunisal.