Propionic Acid Derivatives

PROPIONIC ACID DERIVATIVES

Ibuprofen was the first member of this class to be introduced in 1969 as a better tolerated alternative to aspirin. Many others have followed. All have similar pharmacodynamic properties but differ considerably in potency and to some extent in duration of action (Table 14.2).

The analgesic, antipyretic and anti-inflammatory efficacy is rated somewhat lower than high dose of aspirin. All inhibit PG synthesis, naproxen being the most potent; but their in vitro potency for this action does not closely parallel in vivo anti-inflammatory potency. Inhibition of platelet aggregation is shortlasting with ibuprofen, but longer lasting with naproxen.

Adverse Effects

Ibuprofen and all its congeners are better tolerated than aspirin. Side effects are milder and their incidence is lower.

Gastric discomfort, nausea and vomiting, though less than aspirin or indomethacin, are still the most common side effects. Gastric erosion and occult blood loss are rare.

CNS side effects include headache, dizziness, blurring of vision, tinnitus and depression. Rashes, itching and other hypersensitivity phenomena are infrequent. However, these drugs precipitate aspirininduced asthma.

Fluid retention is less marked than that with phenylbutazone.

They are not to be prescribed to pregnant women and should be avoided in peptic ulcer patient.

Pharmacokinetics And Interactions

All are well absorbed orally, highly bound to plasma proteins (90–99%), but displacement interactions are not clinically significant—dose of oral anticoagulants and oral hypoglycaemics need not be altered. Because they inhibit platelet function, use with anticoagulants should, nevertheless, be avoided. Similar to other NSAIDs, they are likely to decrease diuretic and antihypertensive action of thiazides, furosemide and β blockers.

All propionic acid derivatives enter brain, synovial fluid and cross placenta. They are largely metabolized in liver by hydroxylation and glucuronide conjugation and excreted in urine as well as bile.

Uses

Ibuprofen is used as a simple analgesic and antipyretic in the same way as low dose of aspirin. It is particularly effective in dysmenorrhoea in which the action is clearly due to PG synthesis inhibition. It is available as an ‘overthecounter’ drug.

Ibuprofen and its congeners are widely used in rheumatoid arthritis, osteoarthritis and other musculoskeletal disorders, especially where pain is more prominent than inflammation.

They are indicated in soft tissue injuries, fractures, vasectomy, tooth extraction, postpartum and postoperatively: suppress swelling and inflammation.

Ibuprofen has been rated as the safest conventional NSAID by the spontaneous adverse drug reaction reporting system in U.K. Ibuprofen (400 mg) has been found equally or more efficacious than a combination of aspirin (650 mg) + codeine (60 mg) in relieving dental surgery pain.

Concurrent treatment with ibuprofen has been found to prevent irreversible COX inhibition by low dose aspirin. Thus, it may antagonize the antiplatelet and cardioprotective effect of low dose aspirin.

Naproxen is particularly potent in inhibiting leucocyte migration—may be more valuable in acute gout: dose 750 mg stat followed by 250 mg 8 hourly till attack subsides. It is also recommended for ankylosing spondylitis. Dose should be reduced in the elderly.

Naproxen is marketed as active single S(–) enantiomer preparation, which poses less renal burden. However, some R(+) enantiomer is formed in vivo due to inversion.

Ketoprofen An additional action to stabilize lysosomes and inhibit LOX has been demonstrated with ketoprofen; though anti-inflammatory efficacy is similar to other NSAIDs.

Flurbiprofen more effective than ibuprofen, but gastric side effects are also more. It is used as an ocular anti-inflammatory as well.

OCUFLUR, FLUR, FLURBIN, 0.03% eyedrops, 1 drop 6 hourly.

Choice among different propionic acid derivatives is difficult; naproxen is probably more efficacious and better tolerated in anti-inflammatory doses. It is longer acting and has the advantage of twice daily dosing. However, individuals vary in their preference for different members.