Paracetamol

PHARMACOLOGY:
  • Its mechanism of action is not clearly established.
  • Kit B given at subcentre is Paracetamol
  • It appears that paracetamol inhibits prostaglandin biosynthesis in the central nervous system but not (or hardly) in the peripheral tissues.
  • In any case, paracetamol only has minimal anti-inflammatory action compared to non-steroidal anti-inflammatory agents.
PHARMACOKINETICS:
    Bioavailability Plasma half-life Plasma half-life Active metabolites Elimination
    constant 80% 40 to 60 minutes 2 to 3 hours none predominantly extrarenal
  • Bioavailability is significantly lower when the drug is administered rectally.
DOSE:
Indication Administration Initial loading dose Maintenance dose
Dose Interval Interval
pains of all kinds oral 500 mg 4 to 6 hours 250-1000 mg 4 to 6 hours
Toxic dose:
  • More than 7.5 gm(around 15 tablets)- minimal toxicity 
  • If >15 gm (30 tablets)- severe toxicity 
  • In adult- toxic dose is 150 mg/kg 
  • In children, toxic dose is 200 mg/kg 
  • In presence of chronic disease or malnutrition, even 2gm of paracetamol can be a toxic dose
INDICATIONS:
  • Paracetamol has good analgesic and antipyretic properties.
  • It is suitable for the treatment of pains of all kinds (headaches, dental pain, postoperative pain, pain in connection with colds, post-traumatic muscle pain). 
  • Migraine headaches, dysmenorrhea and joint pain can also be influenced advantageously.
  • In cancer patients, paracetamol is used for mild pain or it can be administered in combination with opioids (e.g. codeine).
  • Paracetamol has been compared to many other analgesics and is considered approximately equipotent to aspirin (acetylsalicylic acid) .
  • Paracetamol is well suited for use in children. 
  • It represents a preferred alternative when aspirin (acetylsalicylic acid) is contraindicated (e.g. because of a history of ulcer or viral infection in the child).
ADVERSE EFFECTS:
  • Blood dyscrasia (e.g. thrombocytopenia), methaemoglobinemia, and hemolytic anemia are very rare. 
  • A minority of the subjects with so-called aspirin intolerance responds to paracetamol with bronchospasms.
  • An adverse cutaneous reaction to an ingested drug with characteristic clinical features is fixed drug eruption.
  • Nephropathy, like drug combinations containing phenacetin.
  • Sterile pyuria
  • When metabolized in the liver, small amounts of an intensely active metabolite, which is normally immediately inactivated by glutathione, are produced. 
  1. An overdose causes a glutathione deficiency; the reactive metabolite may then cause hepatocellular damage and necrosis leading to acute liver failure. 
  2. Toxic effects have been observed in adults treated with doses of more than 10 g (20 tablets). 
  3. However, if there is a pre-existing liver insufficiency, paracetamol can be hepatotoxic even in small amounts.
  4. Paracetamol poisoning can cause metabolic acidosis
  5. Vomiting, pain in abdomen, jaundice and encephalopathy.
  6. History of attempt to commit suicide. 
PRECAUTIONS:
  • The antidote acetylcysteine (e.g. fluimucil) must be administered within 8 to 10 hours when there is intoxication: i.v. infusion of 150 mg/kg in 15 minutes, then 50 mg/kg for 4 hours, and then 100 mg/kg for 16 hours in a 5% glucose solution.
  • PCM Poisoning:
TREATMENT: 
Regimen for Acetylcysteine:
  • 150mg/kg in 200 ml 5% dextrose over 15 min 
  • 50mg/kg in 500 ml 5% dextrose over next 4 hours 
  • 100mg/kg in 1 L 5% dextrose over ensuing 16 hours 
  • Total dose : 300mg/kg over 20.25 hrs
Exam Question
  • Paracetamol poisoning produces Metabolic acidosis 
  • Vesiculobullous lesion healed with hyperpigmentation on the glans soon after taking tablet paracetamol for fever suggest Fixed drug eruption
  • In cases of moderate to severe poisoning of paracetamol, N-acetyl cysteine (mucomyst) should be given orally within 24 hours of overdose to prevent hepatic damage.
  • Paracetamol is one of the safest NSAIDs produces very little GI toxicity and can be administered in patients intolerant to other NSAIDs.
  • Kit B given at subcentre is Paracetamol
  • Sterile pyuria may occur due to Paracetamol
  • A patient presented with vomiting, pain in abdomen, jaundice and encephalopathy. There is a history of attempt to commit suicide. Poisoning suspected is Paracetamol
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