Pharmacology and toxicity of Paracetamol or Acetaminophen (Paracetamol Poisoning) by Dr. Shikha Parmar
Hello students after discussing pharmacology of nsaids and aspirin in today’s video we are going to study pharmacology of paracetamol paracetamol is also called as acetaminophen paracetamol is a very well-known drug it is extensively used as a mild analgesic that is a mild painkiller and antibiotic as it reduces fever unlike aspirin paracetamol has negligible
Anti-inflammatory action now let’s talk about the mechanism of action of paracetamol by now we know that answers like aspirin inhibit the enzyme cyclooxygenase and reduce synthesis of prostaglandins that cause inflammation pain and fever paracetamol also inhibits the enzyme cyclooxygenase and reduce synthesis of prostaglandins but unlike acids paracetamol has no
Peripheral action it does not block cyclooxygenase enzyme expressed at the peripheral sites of tissue injury and inflammation and thus it has no anti-inflammatory action it inhibits centrally that is in the brain paracetamol or acetaminophen is a mild analgesic it reduces mild pain for example during mild headache dysmenorrhea but it is relatively ineffective
When the pain is due to prominent inflammation for example it is ineffective in reducing pain of rheumatoid arthritis it inhibits the enzyme cyclooxygenase that is cox centrally and thereby reduce prostaglandin synthesis in the brain it also increases brain pain threshold and thus person tolerates more pain perception of pain is less it reduces perception
Of pain paracetamol has antibiotic activity it reduces fever paracetamol is one of the best drugs to be used as antibiotic especially in children unlike aspirin paracetamol does not produce ray syndrome in children paracetamol inhibits cyclooxygenase enzyme and reduces synthesis of prostaglandins in hypothalamus that is in the brain now let’s understand the
Pharmacokinetics of paracetamol paracetamol or acetaminophen is well absorbed orally plasma half-life or t-half is two to three hours its duration of action is three to five hours it is metabolized by conjugation it conjugates with glucuronic acid and the metabolite formed is excreted rapidly in the urine now let’s understand the dose of paracetamol paracetamol is
Available in two strengths 325 milligram and 650 milligram usual dose for an adult is 650 milligram four to six time daily but maximum daily dose should not exceed 2600 milligram per day otherwise it can cause liver and kidney toxicity now let’s discuss the therapeutic uses of paracetamol paracetamol is a mild analgesic it can be used for mild headaches mild migraine
Musculoskeletal pain for example pain of joints ligaments tendons etc it is also useful in dysmenorrhea that is in relieving menstrual pain as an antibiotic it is one of the best antibiotic its use is safe in children also unlike aspirin paracetamol does not produce hyperventilation that is paracetamol does not produce respiratory stimulation and hyperventilation
That causes respiratory alkalosis paracetamol does not produce metabolic acidosis paracetamol causes insignificant gastric irritation and thus there is no risk of peptic ulcer it has no anti-platelet effect and thus it does not cause increased risk of bleeding and apart from this it does not produces ray syndrome in children that is it does not reduce liver and
Brain inflammation and therefore its use is safe in children with viral infection allergic or hypersensitivity sensitivity reactions are rare with paracetamol paracetamol can be used in pregnant as well as in the lactating woman now let’s discuss the adverse effects in recommended doses paracetamol is safe as well as well tolerated mild side effects like nausea
And rashes occur sometime that is nausea and rash occur occasionally leukopenia is rare however in high doses paracetamol or acetaminophen can cause liver and kidney damage acetaminophen is very well tolerated but paracetamol toxicity or acute paracetamol poisoning can occur in children it can occur in small children as liver function in children is not very well
Developed so if paracetamol is not completely metabolized and excreted it can cause toxicity in small children in addition to this overdose of paracetamol can cause toxicity in adults also paracetamol toxicity can cause liver damage and renal failure patient can become unconscious and patient can reach coma now let’s understand the mechanism by which paracetamol
Or acetaminophen produce toxicity so let’s first understand how acetaminophen is metabolized in the body acetaminophen is conjugated with the glucuronic acid in the liver to produce non-toxic metabolite that is acetaminophen glucuronite acetaminophen glucuronide is excreted rapidly in the urine but when a very large dose of paracetamol is taken this pathway
Gets saturated that means this pathway gets overloaded and becomes ineffective to metabolize all the paracetamol and this excess paracetamol is shunted to or diverted to another pathway so excess acetaminophen is oxidized by the liver cytochrome 3a4 enzyme acetaminophen is oxidized to a highly toxic and reactive metabolite that is an acetyl parabenzocunon imine
In short nap qi now napqi is conjugated with the glutathione to produce napqi glutathione that is excreted from the body but high doses of acetaminophen deplete glutathione stores so nabqi is neither conjugated to glutathione nor it is excreted from the body and since snapqi is highly toxic and highly reactive it forms covalent bonds uh with the proteins of liver
Cells and renal tubules this causes necrosis of liver cells and renal tubules which in turn causes hepatotoxicity and nephrotoxicity so paracetamol should not be given to small children it should be given to small children only in consultation with physician in adults daily dose of amino fin should not exceed 2600 milligram now let’s understand how paracetamol
Toxicity is treated now patient should be treated as early as possible treatment becomes ineffective if started 16 hours or more after using paracetamol first vomiting is induced or gastric lavage is done gastric lavage is a process to clean out the contents of stomach vomiting or gastric lavage removes paracetamol from the stomach then activated charcoal can be
Given to the person activated charcoal absorbs paracetamol so even if paracetamol is in the stomach it is not absorbed in the blood then an acetylcysteine and acetyl cysteine is a specific antidote of paracetamol it is a glutathione precursor and acetylcysteine regenerates glutathione so that napqoi is excreted from the body so this is how paracetamol toxicity
Is treated so this is in brief about paracetamol if you find the video useful kindly like subscribe and share this video please do not use this information for the clinical purpose this information is meant specifically for the students from their examination point of view you
Transcribed from video
Pharmacology and toxicity of Paracetamol or Acetaminophen (Paracetamol Poisoning) | Dr. Shikha By Dr.Shikha Parmar Classes
