Thread by @AdiG1993

1) A brief review of paracetamol aka PCM

Synthesized by HN Morse at John Hopkins at 1977 --> a derivative of acetanilide and phenacetin.

It has become a common household drug since the 1980s as phenacetin use dropped --> concerns of analgesic nephropathy.

2) It is best known as acetaminophen aka Tylenol in the Western hemisphere.

PCM provides good antipyresis and analgesia --> but anti inflammatory action is minimal.

3) PCM is basically an NSAID that blocks COX1 and COX2 enzymes --> at the peroxide site (distinct among NSAID).

But inflammation raises local peroxide levels --> counters PCM action.

So PCM is a great antipyretic and analgesic but poor anti inflammatory.

4) PCM is a remarkably safe drug --> with very little of the renal, GI, neuro or cardiac complications of NSAID therapy.

Major AE --> acute liver failure at doses usually exceeding 20-25 gm.

So PCM formulation strengths have been reduced to 650/325 mg from 1000 mg.

5) PCM is metabolized by sulfation and glucuronidation.

Overdoses saturate these pathways --> the excess PCM gets shunted to N hydroxylation pathway --> toxic NAPQI --> conjugation with GSH which is gradually depleted --> massive hepatocyte necrosis --> acute liver failure.

6) How does N-acetylcysteine help here?

It replenishes GSH and/or inactivates toxic NAPQI by itself.

But massive hepatic necrosis --> may need liver transplant.

7) Max doses of PCM in the adult?

Approx 3-4 gm/day with lower ranges for alcoholics or those with pre existing liver disease.

Always make sure that the fixed dose combos you are taking don't contain extrq PCM --> a hidden source of overdose.

8) Overall PCM is a remarkable drug with a good safety profile.

It has been in widespread clinical use for more than 50 years --> long before we knew what Dolo 650 was.

I am not an expert but paying 1000 Cr for an OTC drug that has gone off patent --> dumbest idea ever.

*extra

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