Paracetamol !

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•Brand names - Crocin, Dolo, Calpol, Parasafe, Tylenol, Panadol, Paraglass
•Class - NSAID
•Uses - Analgesic & Antipyretic
 (reduces pain and fever)
•Commonly used doses - 325mg, 500mg, 650mg, 1 gram
•Frequency - every 6th hourly 
•Toxic dose - not to exceed 4 grams/ day 

Dose modifications done in - 
• Children    
• Individuals with severe renal impairment 
• Individuals with hepatic impairment / active liver disease (Since it is metabolized in liver, the risk of toxicity is more in individuals with impaired hepatic function. If it cannot be avoided in individuals with hepatic impairment, limit the therapy to short term use with dose not exceeding 2 grams/ day) 
• Pregnancy and lactation - lowest possible dose for shortest possible duration 

Mechanism of Action  - 
•PCM has a central analgesic effect ( mediated through activation of descending serotonergic pathways) and raises pain threshold, thereby reducing pain.
•But it has poor anti inflammatory component and thus is a poor anti inflammatory drug.
•It is a Prostaglandin synthesis inhibitor. It's a poor inhibitior of PG synthesis in the peripheral tissues due to presence of peroxides at site of inflammation but good inhibitor of PG synthesis in the brain. Thereby good analgesic and poor anti inflammatory drug.
•It acts on hypothalamus producing anti pyresis thereby reducing fever.

•Peak plasma time - 
10-60 mins - Oral, Immediate release 
60-120 mins - Oral, Extended release
•Onset - 1 hour 
•Protein bound - only 1/4th is protein bound in plasma and is uniformly distributed 
•Volume of distribution - 1 litre/kg
•Metabolism - In liver via conjugation with glucuronic acid and sulfate. The metabolites are further metabolized via conjugation with glutathione.
•Plasma half life - 2-3 hours 
•Effect after an oral dose last for - 3-5 hours 

Adverse Effects - 
•The usual dose of PCM is well tolerated and has no adverse effects other than nausea and rashes.
•Leukopenia may occur rarely.
•Not to be taken by individuals with allergy or hypersensitivity to PCM.   Anaphylaxis, Stevens Johnson syndrome (SJS), Toxic epidermal necrolysis(TEN) may occur.
•PCM can be taken empty stomach 
(Other NSAIDs like Aspirin and Ibuprofen should not be taken empty stomach as it causes gastric distress) 

In case of Paracetamol poisoning -
•Induce vomiting / Gastric lavage 
• Activated charcoal 
                           Or 
75 mg / kg - PO - every 4-6 hours for 2-3 days 
• N-acetylcysteine replenishes the glutathione stores of liver ,which is an anti oxidant which neutralizes the toxic PCM breakdown products and prevents it's uptake by other hepatic cells.
• However when treating PCM poisoning with N-acetylcysteine, the ingestion-treatment interval is important. The earlier the better. It is practically ineffective to use it 16 hours or more after PCM ingestion.
•Elimination - Conjugates are excreted rapidly in urine.
• N - acetylcysteine ( antidote)     150 mg / kg infusion IV over 15mins ->Same dose - IV for next 20 hours 


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