acetaminophen toxicity, Computer science assignment help

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Computer Science

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Need apa powerpoints on acetaminophen toxicity

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Acetaminophen Toxicity

History
• Synthesized in 1877 in U.S.
• Extensive use began around 1947

• Initially prescription only in the U.S.
• Over the counter status gained in 1960

• Toxic effects first noted in U.S. in 1971

It’s everywhere!
• Acetaminophen is found in over 200 products

Actions
• Analgesia
 Relieves mild to moderate pain
 Efficacy equivalent to salicylates
 Inhibits brain prostaglandin synthetase
 Blocks pain impulses peripherally

• Antipyresis
• Efficacy similar to salicylates
• Inhibits prostaglandin synthetase in the
hypothalamus

Pharmacokinetics
• Absorption
– Rapidly absorbed from the GI tract
– Peak concentration usually occurs between 60 and
120 minutes
– Peak plasma levels almost always occur within 4
hours

Distribution
• V/d - 1.0 - 2.0 L/Kg
• Approximately 20% plasma protein bound
may increase to 50% in overdose

• Has been reported to cross the placenta

Metabolism
– Occurs via several pathways in the liver






52% by sulfation
42% by glucuronidation
2% excreted unchanged in the urine
4% biotransformed by C-P450 MFO system into
an active intermediate NAPQI

NB: When large doses of APAP are ingested, both
the glucoronidation and sulfation pathways
become saturated, shunting more APAP toward
the P-450 system and increasing NAPQI
formation.

Metabolism
• When glutathione depletes to 30% of normal, NAPQI
accumulates.
• The NAPQI arylates to protein in the cytosol and
endoplasmic reticulum in the centrilobular zone of the
liver, producing cell necrosis and death.
• NAPQI is neutralized by glutathione
• NAPQI contains a sulfhydryl group. If all glutathione is
used up, other sulfhy...


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