Important Non Steroidal Anti Inflammatory Drugs

Apart from Aspirin and Paracetamol, already discussed, following are the important non-steroidal anti-inflammatory drugs:

Diflunisal

Difluoro phenyl derivative. Because of chain structure cannot cross blood brain barrier. So cannot be used as anti-pyretic.

It can be used as anti-inflammatory and analgesic peripherally.

As cannot cross BBB, so CNS effects like salicylism, auditory effects are not present.

Uses

1. Rheumatoid arthritis
2. Ankylosing spondylitis
3. Osteomyelitis

Chances of GI bleeding are much less.

Ibuprofen

Actions are also dose related (400mg tablet). Anti-inflammatory effects at 2400 mg/day (2 tablets 3 times a day).

Below this dose, used as anti-pyretic and analgesic.

GI bleeding from use of aspirin

Used in treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and acute gout.

Also available as ointment and cream and applied for muscle sprains.

Adverse effects

If used over prolonged periods, there are chances of renal failure, interstitial nephritis.

Indomethacin

Slightly different, as is selective for COX-1, slightly more than the other.

Mechanism of action is same like the others.

Therapeutic uses

Can be used as analgesic, anti-pyretic and anti-inflammatory.

It cannot be used for longer durations due to fear of toxicity which occurs in 35-50% of the patients on prolonged use.

Indications

Patent ductus arteriosus

When fetal lungs are not functional and liver is only partially, placenta provides oxygen and nutrition and helps in excretion of wastes. Certain changes take place when born. Closure of patent ductus arteriosus occurs, during fetal life prostaglandins keep it patent under COX-1 influence. In some individuals, even after birth, closure does not occur. If detected earlier, this drug can help in closure. Later on surgery is indicated.

Adverse effects

1. 25% of patients suffer from headache –frontal, on prolonged use

2. psychosis, hallucinations

3. chances of agranulocytosis

4. pancytopenia

5. thrombocytopenia

6. GI bleeding

7. Gastropathy

Probenecid prolongs the half life of Indomethacin because it decreases its renal and biliary clearance.

Piroxicam

Available as injections, capsules, tablets, gel for local application.

Most important is that it has a very long half life about 46-72 hours. Can be used once a day.

Uses

1. Post op pain
2. Renal colic
3. Other indications are anti-inflammatory effects

Diclofenac Sodium 

Available as potassium or sodium salt. Potassium salts are better absorbed. Preparations are available as tablets, injectables, gels for topical use, eye drops.

Uses

1. Post op pain
2. Renal colic
3. Rheumatoid arthritis, acute gout, ankylosing spondylitis
4. Eye drops for post op inflammation of eye
5. Gel (topical) for solarkeratoses and musculoskeletal pain
6. Rectal suppositories for post op nausea and pre-emptive analgesia
7. Another preparation is available in combination with misoprostol, used for prevention of gastropathy. In combination, the drug is tolerable for patients of GI ulcers.

Fenoprofen

Causes interstitial nephritis

Flurbiprofen

Propionic acid derivative.

Uses include:

1. Dose of 200-400 mg with aspirin and other in clinical trials for rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, gout.
2. In topical eye drops, prevents intra op miosis
3. For peri op analgesia in nose, ear and neck surgeries (I/V)
4. In lozenge form for sore throat

Adverse Drug Reactions

Cog wheel rigidity

Sulindac

Sulfoxide. Prodrug.

Metabolism:

Metabolized to active sulfide metabolite, undergoes enterohepatic circulation and prolongation of half life.

Uses

1. Rheumatoid arthritis
2. Suppress familial intestinal polyposis
3. May decrease the development of colon, breast and prostate cancers.

Adverse Drug Reactions

1. Stevens Johnson epidermal necrolysis syndrome
2. Thrombocytopenia
3. Agranulocytosis
4. Nephrotic syndrome
5. Increased ALT and AST levels
6. Cholestatic jaundice

Tolmetin

Efficacy is similar to other NSAIDS except that it is ineffective in treatment of gout. Adverse drug reactions include thrombocytopenic purpura.

Tiaprofen

Racemic propionic acid derivative

Half life is 1-2 hours (however in elderly it is 2-4 hours)

It decreases renal uric acid reabsorption leading to hypouricemia

Selective COX-2 inhibitors

COX-2 is constitutive at two places:

1. Brain
2. Kidneys

Not in stomach.

Within therapeutic range, as more selective, chances of GI problems are far less. Benefits are lost at higher dose, as selectivity is lost.

As COX-2 is constitutive in kidneys, chances of renal toxicity in renal compromised or CCF or cirrhosis of liver, as blood flow is then maintained by prostaglandins mediated COX-2. When blocked, there are increased chances.

Uses

Only for anti-inflammatory use, rheumatoid arthritis, ankylosing spondylitis, etc.

No anti-platelet or anti-pyretic actions, chances of stroke and thrombotic events are increased. This is one reason why drugs like Valdecoxib and Roficoxib have been withdrawn.

Celecoxib

10-20 times more selective for COX-2 than COX-1. Adverse drug reactions include:

1. Edema
2. Hypertension
3. Rashes

Celecoxib and warfarin are both metabolized by cyp2c9.

Valdecoxib

Diaryl substituted isoxazole. Used in rheumatoid arthritis and as analgesic (20 mg, twice daily).

Adverse drug reactions include:

1. Increased CVS risks
2. Stevens Johnson syndrome

So withdrawn.

Etoricoxib

Structurally similar to diclofenac, so hepatic functions should be monitored.

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Non Steroidal Anti Inflammatory Drugs -General Aspects

AspirinParacetamol