Acetaminophen

Action:

It inhibits prostaglandin synthesis in CNS (so analgesic and anti-pyretic) but has less effect on COX so (weak anti-inflammatory).

Therapeutic Uses:
It is used as analgesic and anti-pyretic. It is analgesic /anti-pyretic of choice for children with viral infections or chicken pox.

Drug interactions:
It does not antagonize the uricosuric agent (probenecid) and so may be used in patients with gout who are taking this drug.

Pharmacokinetics:
Rapidly absorbed from GI tract. 1st pass metabolism occurs in the luminal cells of the intestine and in the hepatocytes. It is conjugated in the liver to form inactive glucoronidated or sulfated metabolites. It is excreted in the urine.

Adverse effects:
It may cause skin and minor allergic reactions. Prolonged use may cause renal tubular necrosis and hypoglycemic coma.

Celecoxib

Action:

Inhibition of COX-2 by celecoxib is time dependent and reversible.

Pharmacokinetics:
It is readily absorbed orally. Its peak concentration is approximately 3 hours. It is metabolized in the liver by cytochrome P450 (CYP2C9). It is excreted in feces and urine. Its half life is 11 hours, so its dose is adjusted according to once a day.

Adverse Effects:
It may cause abdominal pain, Diarrhea, Dyspepsia and Kidney toxicity may also occur.

Drug interactions:
It inhibits CYP2D6 and so can elevate levels of ß-blockers, anti-depressants and anti-psychotic drugs.

Fluconozole, fluvastatin and zafirlukast may increase serum level of celecoxib.

Precautions:

It should be avoided in patients;

- with chronic renal insufficiency

- Severe heart disease

- Volume depletion

- Hepatic failure

COX-2 selective NSAIDs

COX-2 is better in providing space for inhibitors than COX-1.


Uses:
It is used as a pain reliever.
Adverse effects:
It may cause renal insufficiency and hypertension.

Diflunisal

It is diflurophenyl derivative of salicylic acid.


Action:
3-4 times more potent than aspirin but cannot be used as antipyretic.

Pharmacokinetics:
It is not metabolized to salicylate and therefore cannot cause salicylate intoxication. It cannot enter CNS, so cannot relieve fever.

Nabumetone

Same as aspirin with little side effects.

Tolmetin

Same as aspirin with little side effects.

Ketorolac

Action:

Similar to NSAIDs.

Administration:
It can be administered

• Orally

• Intramuscularly (for post operative pain)

• Topically (for allergic conjunctivitis)

Pharmacokinetics:
It undergoes metabolism in the liver. The drug and its metabolites are excreted in the urine.

Adverse effects:
It is similar to NSAIDs.