What is paracetamol (acetaminophen)?

Paracetamol is also called acetaminophen, which is most commonly used medicinally that help to treat fever (reduce a high body temperature) -antipyretics, reduce mild to moderate body pain (analgesic), and reduce inflammation (redness, swelling, and pain) in your body.

It is a deethylated active metabolite of phenacetin ( banned nowadays because it was implicated in analgesic abuse nephropathy), was also introduced in the last century but has come into common use only since 1950.

Formula: C8H9NO2
Molar mass: 151.163 g/mol
Generic name: N-acetyl-p-aminophenol
Soluble in: Alcohol and water
Trade and brand name: Dymadon®, Lemsip®, Panadol®, Panamax®, Tylenol®
People also search for: Aspirin, cetamol, Ibuprofen, Metamizole, Naproxen, many more.

How does it work? (Mechanism of action)

It acts on the hypothalamus to produce antipyresis (reduce fever) and it is a poor inhibitor of prostaglandin synthesis in peripheral tissues but more active on cyclo-oxygenase (COX) enzymes in your brain.

Pharmacokinetics (Absorption, Distribution, Metabolism, and Excretion)

Acetaminophen is effective by oral and parenteral routes. It is well absorbed orally, uniformly distributed in your body, and only about 1/4th is bound to plasma protein. Metabolized in the liver by glucuronide and sulfate conjugation.

The conjugate metabolites are excreted rapidly in urine (principally as acetaminophen glucuronide with acetaminophen sulfate/ mercaptate). Plasma half-life (T1/2) is 2-3 hours. Effects occur after an oral dose lasts for 3-5 hours.

Usually, Drugs will be used after your doctor or consultant prescript;

Dose: 325–650 mg (for children 10–15 mg/kg) 3–5 times a day.
Dosage forms: tablet (325 mg and 500 mg), caplet (325 mg, 500 mg, and 650 mg0, capsule (325 mg and 500 mg), tablet chewable(80 mg), solution or suspension (160 mg/5ml), liquid oral (160-500mg/5 ml), syrup oral (160 mg/5ml)

Generally, Paracetamol 500 mg dosages are commonly used in adult human beings.

Tylenol extra strength (i.e. 500 mg/tablet or capsule): It is not to exceed 3 g/day; under the supervision of healthcare professionals such as doctors, daily doses of up to 4 g/day may be used.

Uses

It is an ‘over counter drugs’, there are the following uses

• Antipyretic action: to reduce your body temperature during a fever.
• Analgesic action: to relieve toothache, headache, myalgia, dysmenorrhoea, mild migraine, musculoskeletal pain, etc.
• Analgesic and antipyretic action: Patients with peptic ulcer, hemophilia, bronchial asthma, and children
• Rheumatoid arthritis
• Osteoarthritis

Side effects

It is a safe and well-tolerated drug but there are very rare side effects but sometimes side effects on the basis of their dose and duration of drugs you can use.

• Nausea and rashes (occasionally)
• Some rare side effects:
  • Leukopenia (reduce white blood cells)
  • Angioedema (swelling and redness in deeper layers of your skin)
  • Disorientation (altered mental state)
  • Dizziness
  • Hyperammonemia (raised the level of ammonia in your blood)
  • Stevens-johnson syndrome (a serious disorder of the skin and mucous membrane)
  • Urticaria
  • Gastrointestinal hemorrhage
  • Agranulocytosis (deficiency of granulocytes in your blood)
  • Neutropenia (decreased neutrophils)
  • Pancytopenia ( few red blood cells, white blood cells, and platelets)
  • Toxic epidermal necrolysis
  • Pruritic maculopapular rash
  • Thrombocytopenia (low blood platelet count)
  • Hepatotoxicity (injury or liver damage)-chronic use or acute overdose condition
  • Liver failure
  • Nephrotoxicity (toxicity in the kidneys)-chronic use
  • Pneumonitis (inflammation of lung tissue)
  • Anaphylactoid

Contraindications

• Hypersensitivity reaction
• Severe active liver disease

Is paracetamol safe in pregnancy?

In general, paracetamol drugs cross the placenta and can be detected in cord blood, newborn serum, and urine immediately after delivery of the baby. The teratogenic effects are not reported when mothers use drugs during pregnancy.

If paracetamol used in normal doses during pregnancy which is not associated with an increased risk of miscarriage or stillbirth; however, an increase in fetal death or spontaneous abortion may be seen in some mothers when paracetamol overdose if treatment delayed.

In some cases, asthma and wheezing occur in early childhood which is associated with frequent mother use of acetaminophen drug during the pregnancy period.

Is paracetamol safe in lactation?
Drugs are excreted through milk; in general, breastfeeding is generally acceptable if relative infant dose is less than 10 percent; avoid breastfeeding when relative infant dose increases more than 25 percent.

Acute paracetamol poisoning

When acute overdosage mainly causes hepatotoxicity, the symptoms are nausea, vomiting, abdominal pain, diarrhea, hypotension, hypoprothrombinemia, hypoglycemia, coma, etc. And death usually occurs due to hepatic necrosis.

Mechanism of toxicity

High doses of acetaminophen cause depletion of glutathione levels. In the absence of glutathione compounds, toxic metabolites (N-acetyl-p-benzoquinone imine (NAPQI)) bind covalently with proteins in your liver and kidney causing necrosis.

The toxic metabolites of acetaminophen are detoxified by conjugation with glutathione and get eliminated. Premature infants and alcoholics people are more prone to hepatotoxicity.

Treatment of acute paracetamol poisoning

• If patients are brought early then vomiting should be induced or gastric lavage was done.
• Active charcoal is administered orally to decrease the absorption of acetaminophen from the gut.
• Other supportive measures are; N-acetylcysteine (150 mg/kg) infused IV over 15 minutes followed by the same dose IV next 20 hours.
  • N-acetylcysteine or oral methionine replenishes the glutathione stores of your liver and protects liver cells, and prevents the binding of toxic metabolites to other cellular constituents.
• Acidosis done by drug omeprazole.
• Hemodialysis may be done in the case of acute renal failure.

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