Acetaminophen is a weak inhibitor of COX1 and COX2 in peripheral tissues which makes it effective for relieving fever and pain without increasing bleeding risk like NSAIDs. It is considered safe for children as it does not cause Reye's syndrome like aspirin. Acetaminophen is rapidly absorbed from the GI tract and conjugated in the liver to inactive metabolites, but in large doses the reactive metabolite NAPQI can deplete glutathione leading to hepatic necrosis in sensitive individuals.

1. ACETAMINOPHEN

2. ACETAMINOPHEN
Acetaminophen is the active metabolite of
phenacetin and is responsible for its analgesic
effect
• Phenacetin, a prodrug that is metabolized to
acetaminophen, is more toxic than its active
metabolite .
• STRUCTURE OF
ACETAMINOPHEN:-

3. ACETAMINOPHEN
• Acetaminophen (N-acetyl-p-aminophenol or
APAP) inhibits prostaglandin synthesis in the
peripheral tissues. But more active on COX in
CNS.
Effects:-
1- ANTIPYRETIC 2- ANALGESIC
• It is a weak COX1 &COX2 inhibitor in peripheral
tissues(due to inactivation).
• It does not affect PLATELET function or increase
Bleeding Time.
• It is not considered an NSAID.

4. • In contrast to aspirin, paracetamol does not
stimulate respiration or affect acid-base
balance;
• does not increase cellular metabolism.
• It has no effect on CVS.
• It does not affect platelet function or clotting
factors.

5. THERAPEUTIC USES:-
• Treatment of fever & Relief the pain
It is useful :-
• with gastric risk with NSAIDs
• Acetaminophen is analgesic /antipyretic of
choice for children with viral infections or
chickenpox (due to the risk of Reye syndrome
with aspirin)

6. PHARMACOKINETICS:-
It rapidly absorbed from GI tract and undergoes
First pass metabolism
• It Conjugated in Liver to form GLUCURONIDATED
(inactive) / sulfated metabolites.
• A portion of acetaminophen is hydroxylated to
form N-acetyl-p-benzoquinoeimine /NAPQI
( a highly reactive metabolite that can react with
sulfhydryl groups and cause liver damage)

7. • At NORMAL doses,
NAPQI reacts with sulfhydryl group of GULTATHIONE
(produced by liver) -----forming a Non-Toxic Substance.
• HALF-LIFE:-
The half-life of acetaminophen is 2–3 hours and is relatively
unaffected by renal function.
With toxic doses or liver disease, the half-life may be
increased twofold or more.
• EXCRETION:-
Acetaminophen and its metabolites excreted in Urine.
• ROUTE OF ADMINSTRATION :-
IV & rectal formulation-

8. ADVERSE EFFECTS:-
At normal therapeutic doses ---few adverse effect
• At large doses , GULTATHIONE in the liver depleted
NAPQI reacts with the sulfhydryl group of hepatic proteins.
• HEPATIC NECROSIS (a serious and potentially life threatening
condition)
• Patients with hepatic disease viral hepatitis or history of
alcoholism are at the higher risk of acetaminophen induced
Hepato-toxicity
• It should be avoided in patients with severe hepatic
impairment.