Diclofenac

Action:

It is more potent in action than naproxen and indomethacin. It is cyclooxygenase inhibitor.

Pharmacokinetics:
It accumulates in the synovial fluid. It is excreted into urine.

Therapeutic Uses:
It is used for the long term treatment of:
• Rheumatoid arthritis
• Osteoarthritis
• And ankylosing spondylitis.

Adverse effects:
Its adverse effects are similar to those of the NSAIDs.

Fenamates

They are used as a pain releiver.

Adverse effects:


• Diarrhea

• Hemolytic anemia (rare)

Oxicam derivatives

Action:

Meloxicam is relatively COX-2 selective.

Therapeutic uses:
(Similar to that of Acetic acid derivatives)

Pharmacokinetics:
These have usually longer half lives. Piroxicam and its metabolites are excreted in the urine whereas meloxicam and its metabolites are excreted equally in the urine and feces.

Adverse effects:
It may cause GI disturbances.

Sulindac

It is used for:


• Rheumatoid arthritis

• Ankylosing spondylitis

• Osteoarthritis

• And acute gout.

Indomethacin

It is used for:


• Acute gouty arthritis

• Ankylosing spondylitis

• And osteoarthritis of the hip.

Propionic acid derivatives

Mechanism of Action:

These are reversible inhibitors of cyclooxygenase.

Action:
These inhibit the synthesis of prostaglandins but not that of leukotrienes.

Pharmacokinetics:
It is absorbed orally. It has the ability to bind to plasma albumin. It undergoes hepatic metabolism and excreted by the kidney.

Therapeutic Uses:
It is used as anti-inflammatory mostly in the chronic treatment of rheumatoid arthritis and osteoarthritis. It is also anti-pyretic and anti-inflammatory.

Adverse effects:
• Headache, tinnitus and dizziness.
• GI disturbance ranging from dyspepsia to bleeding.

Aspirin and other salicylates

Mechanism of Action:

Aspirin reduces pain at subcortical sites also.

Action:

Analgesic:

There is sensitization of nerve endings to the action of bradykinin, histamine and other chemical mediators by PGE2, thereby, reduce pain.

It is used to relieve low to moderate pain coming from integumental structures rather than that coming from viscera.

Anti-pyretic:

Aspirin stops PGE2 production. Also there is heat dissipation (of febrile subjects) as a result of peripheral vasodilatation and sweating and in this way it acts as anti-pyretic.

Anti-Inflammatory:
Aspirin reduces inflammation in which PG acts as mediators.

Respiratory Actions:
It causes increased alveolar ventilation and increased respiration.

If the dose exceeds the therapeutic range it may cause some side effects.

Gastrointestinal effects:

Aspirin causes epigastric distress, ulceration or hemorrhage.

Effect on platelets:
It causes reduced platelet aggregation.

Actions on kidneys:
It may cause retention of water and sodium resulting in edema and hyperkalemia.

Pharmacokinetics:
Absorption:
Salicylates are well absorbed through the undamaged and normal skin. On the other hand, unionized form of salicylates are passively absorbed by the stomach and small intestine.

Distribution:
They can pass through the Blood brain barrier except diflunisal.

Metabolism:

Elimination:
Plasma half life of salicylates is 3.5 hours. Salicylate is converted by the liver to water soluble conjugates. It is at last cleared by the kidney.

Doses:
Low doses act as Analgesic

High doses act as Analgesic and anti-inflammatory

Therapeutic Uses:
1. It is used as Anti-pyretic and analgesic.
2. Salicylic acid is also used topically for the treatment of corns, calluses and epidermophytosis.
3. It is also used prophylactically for the heart.
4. It may also help in the reduction of colon cancer.

Adverse effects:
1. GI disturbance.
2. Prolonged bleeding time due to the inhibition of the platelet aggregation.
3. Reduced respiratory activity.
4. Hypersensitivity reactions.
5. Reye’s syndrome.
6. Salicylates in toxic quantities may cause hyperthermia due to uncoupling of oxidative phosphorylation.