ANTIPYRETICS

ANTIPYRETICS
• Antipyretics are drugs
capable of reducing body
temperatures in patients
with fever
• Antipyretics do not reduce
normal body temperature
INDUCTION OF FEVER
 Commonly used antipyretics

• Aspirin
• ƒIbuprofen
• ƒMetamizol
• ƒParacetamol
 ASPIRIN
• Acetyl salicylic acid
• MA: inhibits biosynthesis of PGE2
• Well absorbed → hydrolyzed in the liver →
salicylic acid → excreted through the
kidney
• Dosage (as antipyretic):
1. ƒadult: 325 – 650 mg every 4 – 6 h
2. ƒchildren: 10 mg/kg BW every 4 – 6 h
(max. ≤ 3,6 g/day)
• Over-the-counter (OTC) drug
 Side effects

• G
ƒ I disturbance: abdominal pain,
nausea, dyspepsia, gastric/duodenal
ulcer, diarrhea
• ƒInhibition of platelet aggregation →
prolonged bleeding time
• Reye’s syndrome: may occur (rare)
if aspirin is given to children with
viral infection.
• Symptoms: coma, seizure, cerebral
edema, multi-organ failure and
death
• Salicylate intoxication →
“salicylism” characterized by
vomiting, tinnitus, hearing loss,
hyperventilation, vertigo.
• Tinnitus usually occur when
plasma level of salicylic acid
reaches 200-450 μg/mL
(antipyreic dose of aspirin →
plasma level of < 60 μg/mL)
 IBUPROFEN

• Is a derivative or propionic
acid
• Analgesic and antipyretic
effect: equal to aspirin
• Antiinflammatory effect: less
than aspirin
• Side effect: GI disturbances
(less than aspirin)
Methampyron (dipyron,
metamizole)
• Is a pyrazolon derivative with weak
antiinflammatory effect
• SE: agranulocytosis, aplastic anemia,
thrombocytopenia → prohibited in many
countries
• Indication:
1. Analgesic and antipyretic for conditions
failing to respond to the more safe agents
2. When parenteral administration is
needed
 Paracetamol (acetaminophen)

• Paracetamol has a very weak

antiinflammatory effect, but it is
used in arthralgia because of its
good analgesic effect
• ‰Mechanism of antipyretic:
Inhibition of PGE2 production in
the preoptic region of
hypothalamus
Pharmacokinetics
• ƒWell absorbed through oral
route, metabolized in the liver,
and excreted through the kidney
• A
ƒ minor but highly reactive
metabolite N-acetyl-p-benzo-
quinone imine (NAPQI)is
hepatotoxic and nephrotoxic
• ƒT½ is 2-3 hours, but may be
doubled if very high dose is
given
 SIDE EFFECT

• Relative safe, also in pregnancy

• In therapeutic dose (3-4 x 500 mg/day) :
does not affect the CVS system,
respiration, platelet function and blood
coagulation
‚ Does not irritate or induce bleeding of
the stomach
• In a very high dose (10-15 g or 150-250
mg/kg BW) → NAPQI ↑↑→ depletion of
body GSH (glutathion) → liver necrosis.
Drug of choice for this condition: N-
acetylcystein (given in 24 h)
TERIMA KASIH