Paracetamol

BRAND NAMES:
Disprol -  Disprol contains acetaminophen as the main active ingredient available in the form of capsules, intravenous injections, tablets, suppositories, solutions, oral granules, suspensions, and chewable tablets.
Combiflam -  It is mainly composed of two drugs, ibuprofen, and paracetamol, available in the form of tablets.
Panadol - Panadol 500 mg is a film-coated tablet available in the market that contains acetaminophen as the major active ingredient which relieves faster than the other paracetamol tablets.
Calpol – Acetaminophen is the main active ingredient present in the calpol with a strength of 500 mg, which helps in relieving pain and reduces fever.
PCM injection  - It contains paracetamol as the main active ingredient which is available in the form of an injection with a strength of 150 mg and is used to relieve pain and fever.
Dolo 650 -  It contains acetaminophen with a drug composition of 650 mg, mostly available in the market in the form of tablets.
MECHANISM OF ACTION:
By blocking COX-1 and COX-2, two isoforms of cyclooxygenase involved in prostaglandin synthesis, acetaminophen raises the threshold for pain. The chemicals are known as prostaglandins, which cause pain perception. It has no anti-inflammatory effects on the periphery since it does not inhibit cyclooxygenase in peripheral tissues. COX is indirectly blocked by paracetamol. A distinct variation of the COX enzyme, apart from the well-known COX-1 and COX-2 variants, is specifically blocked by it. The name COX-3 has been applied to this enzyme. Acetaminophen's antipyretic effects are probably due to its direct action on the brain's heat-regulating centers, which causes peripheral vasodilation and a reduction in body temperature and perspiration.
PHARMACOKINETICS:
Absorption:  When taken orally, paracetamol has a bioavailability of 70 to 90% and is quickly absorbed from the digestive system. When taken orally, it takes 30 to 60 minutes to reach its peak plasma concentration. When paracetamol is administered intravenously, peak plasma concentrations rise faster. 
Distribution: The volume of distribution is approximately 0.9L /Kg.
Metabolism:  It is majorly metabolized in the liver, and the major metabolites are sulfate and glucuronide conjugates.
Excretion: 85 to 95% of the dose is excreted through urine within 24 hours.
PHARMACODYNAMICS:
Paracetamol is a P-aminophenol derivative that exhibits analgesic and antipyretic activities. It does not possess anti-inflammatory activity. It is thought to produce analgesia through a central inhibition of prostaglandin synthesis. It appears to exert its effects through cyclooxygenase and the action of its metabolite.
DOSAGE AND ADMINISTRATION:
Paracetamol is available as oral, rectal, and IV routes. Compared to IV infusion, oral and rectal infusion are more beneficial, whereas IV infusion has limited efficacy. Based on the patient's condition and age, the dosage will be administered.
• For pain and fever, adults and adolescents weighing 50 kg or more should take 1000 mg of paracetamol every 6 hours or 650 mg every 4 hours. The maximum single dose should not be more than 1000 mg at 4-hour intervals. The maximum daily dosage of paracetamol should not exceed 4000 mg.

• Adults and adolescents under 50 kg should take 12.5 mg/g or 15 mg/kg every 4 to 6 hours. The interval between dosages should be at least four hours, with a maximum of 115 mg/kg. Paracetamol should be used at a maximum of 3750 mg per day, or 75 mg per kilogram.
CONTRAINDICATIONS:
Paracetamol is contraindicated for hypersensitivity, active hepatic disease, and severe hepatic impairment.
DRUG INTERACTIONS:
It includes some medications, and while interacting with paracetamol, it may cause some adverse effects and also decrease the functioning of the drug. So before taking paracetamol, it is important to discuss with the doctor the medications that are already used for some other treatments. Below are the few drugs that interact with paracetamol.
• Blood thinners - Warfarin
• Antibiotics: – Chloramphenicol, Rifampicin
• Antinausea agents  -  Metoclopramide, domperidone
• Anticonvulsants: – Lamotrigine, phenytoin, carbamazepine
• Analgesics – Aspirin
• Antigout medicines-Probenecid
• Antitubercular drug isoniazid
• Cholesterol-lowering drugs—cholestyramine
FOOD INTERACTIONS:
Avoid cabbage, carbohydrates, sprouts, and broccoli. And avoid taking alcohol.
ADVERSE EFFECTS:
• Shortness of breath
• Skin rash 
• Mouth ulcers
• Hives
• Swelling of throat, tongue, and face.
• Bruising or bleeding
• Loss of appetite
• Yellowing of the eyes and skin.
TOXICITY:
Overdose of paracetamol can cause some toxic effects.
• Nausea
• Extreme tiredness
• Abdominal pain
• Loss of appetite
• Vomiting