February 1, 2023

Acetaminophen Pharmacology. Paracetamol Mechanism of Action Student Lecture – 🩺 Complete Lectures on sqadia.com

Skyday.com is advancing towards special video series where we are specifically covering major aspects of pharmacology watch out for more subject related series very soon on skydia.com whenever normally you experience pain which analgesic or which medicine do you prefer are you thinking about paracetamol well it’s not just you acetaminophen or more commonly known

As paracetamol is the most commonly taken analgesic worldwide and not only that it is recommended as a first line therapy in pain conditions by the world health organization now acetaminophen is often misinterpreted as non-steroidal anti-inflammatory drug or nsaid well this is because acetomenophen has some answer-like properties for example it is antipyretic or

It means that it reduces fever it has analgesic properties means that it relieves pain but it lacks the anti-inflammatory properties as it doesn’t reduce inflammation an anticoagulative activity is also lacking that means that it doesn’t prevent blood clotting now all these properties are commonly associated with these drugs so it is not considered to be an nsaid

Acetaminophen is basically an n-acetyl p aminophenol now as the name suggests it contains a phenol with an a minor group at the para position and an acetyl group attached with the nitrogen of the amino group now acetaminophen is the active metabolite of phenycitin now what is this drug fenestatin well remember the phenetin is a pro drug that is metabolized to

Acetaminophen but it’s more toxic than its active metabolite and has no rational indications well it was actually banned in most countries from the late 1960s because it causes renal diseases and cancers of the upper urinary tract so moving forward let’s talk about acetaminophen in more detail we’re going to talk about its mechanism of action its therapeutic uses

Its pharmacokinetics and will also go into into detail about the adverse effects and the toxic reactions it causes inside the body so stay tuned hi there now before we jump into the video i have a very important question for you have you subscribed to our channel if not then subscribe right now to stay updated with the latest and brand new scalia.com lectures and

Click on the bell icon to stay notified about new releases we upload a full lecture every single week with some short videos sprinkled in between so that being said now that you’ve subscribed let’s return to the lecture well actually the exact mechanism of action of acetaminophen has not been fully established well despite this it is often categorized alongside

Nsaids due to its ability to inhibit the cyclooxygenase or this corks pathways well it is thought to exert central actions which ultimately lead to the alleviation of pain symptoms one theory is that acetaminophen increases the pain threshold by inhibiting the now wait a minute do you remember what is cyclooccitane is responsible for well let’s recall that

Cyclocyclooxygenase is also known as the glandine endoperoxide synthase or ptgs it is an enzyme that is responsible for the formation of prostenoids including thromboxane and prostaglandins now these originate from arachidonic acid which is actually in a polyunsaturated fatty acid present in the phospholipid of membranes of the body’s cells so what is acetaminophen

Doing it’s actually inhibiting the two isoforms of cyclooxygenases cox-1 and cox-2 that are involved in the prostaglandin synthesis now what are you must be wondering what are prostaglandins well you are already familiar that prostaglandins are responsible for eliciting pain sensations so we can relate the inhibition of its synthesis with the analgesic activity of

Acetaminophen remember that acetaminophen does not inhibit cyclooxygenase in the peripheral tissues and therefore it has no peripheral anti-inflammatory effects now although acetylcyclic acid or aspirin is an irreversible inhibitor of corks and it directly blocks the active site of the enzyme but studies have shown that acetaminophen or paracetamol blocks the

Corks indirectly now there are some other studies that actually suggest that acetaminophen crosses the blood-brain barrier and selectively blocks a variant type of the cox enzyme which is referred to as cox-3 now this will block the formation and release of prostaglandins in the central nervous system now this inhibits the direct action of endogenous pyogenes

On the heat regulating centers in the brain that is hypothalamus now this results in the peripheral vasodilation sweating and loss of body heat that is resulting in its antipyretic effect now if we talk about the therapeutic uses of acetaminophen this drug is useful in mild to moderate pain such as headaches myalgia postpartum pain menstrual periods toothache

And may also be used in colds or sore throats and reactions to vaccinations and to reduce fever overall moreover it is suitable for the substitute of the analgesic and antibiotic effects of aspirin especially for those patients with gastric complaints like the one with a history of peptic ulcer disease and those in whom prolongation of bleeding time would be

Disadvantaged like people with hemophilia and those who do not require the anti-inflammatory action of aspirin it is preferred to administer acetaminophen rather than aspirin in patients in which aspirin precipitates the bronchospasm remember that acetaminophen is the analgesic or antibiotic of choice for children with viral infections like chickenpox but it is

Because aspirin may trigger ray’s syndrome which is a rare disorder that causes brain and liver damage it usually occurs in children who have recent viral infections such as like i said chicken pox or the flu acetaminophen may also be used in patients with gout who are taking uricosauric agents like probenicet or sulfin pyrozone drugs as acetaminophen does not

Antagonize these agents while on the other hand aspirin reduces the efficacy of these drugs so this is why acetaminophen is more preferred in these cases now talking about the dosage of acetaminophen it is usually administered orally as a tablet or capsule in adults and in forms of syrup or oral solution or suspension for children now other routes such as

Intravenous as well as rectal suppository are available for both adults and proteatic patients now moving on to the proper dosage of this drug in adults acute pain and fever may be effectively treated with almost 325 to 500 milligrams four times daily and it is now recommended not to exceed four grams per day in most cases on the other hand in children the dosage

Is 10 to 15 milligrams per kg per dose this is usually given orally every four to six hours and must not exceed more than five doses or 2.6 grams in 24 hours and in the case of hepatic impairment we should try to avoid acetaminophen as much as possible or if it is used therapy should be limited to short-term use at doses not to exceed 2 grams per day the use of

Normal doses during pregnancy are not associated with increased risk of miscarriage or cell stillbirth however the case of maternal overdose increase in the fetal death or spontaneous abortion may be seen if treatment is delayed wheezing in asthma in early childhood is also associated with frequent maternal use of drug during pregnancy if we talk about lactation this

Drug is usually excreted in milk but in general breastfeeding is accepted if the relative infant dose is less than 10 and breastfeeding must be avoided when this relative dose increases to more than 25 percent like i told you earlier acetaminophen is administered overly and its absorption is related to the rate of gastric emptying at the peak blood concentrations

Are usually reached within 30 to 60 minutes acetaminophen is slightly bound to plasma proteins so it means that it is well distributed a significant first pass metabolism occurs in the luminal cells of the intestine and in the hepatocytes now under normal circumstances acetaminophen is conjugated in the liver to form inactive gluconated or sulfated metabolites

A portion of acetaminophen is hydroxylated to form an acetyl benzo amino quinone or it is also known as n-acetyl parabenzo quinone amine or napqi it is a highly reactive and potentially dangerous metabolite and this toxic metabolite in the setting of large toxic doses of acetaminophen reacts with the sulfital groups in the hepatic cell proteins and it forms a

Substance that causes cell death and damages the liver now on the other hand at normal doses of acetaminophen the n-acetyl benzoamino quinone reacts with the sulfite group of glutathione and it ultimately forms a non-toxic substance now after all of this has occurred acetaminophen and all its metabolites are then excreted in the urine what about the half-life

Of acetaminophen well the half-life is two to three hours and it is relatively unaffected by the renal function now with toxic doses or liver disease the half-life may increase two-fold or even more now remember with normal therapeutic doses acetaminophen is virtually free of any significant adverse effects however in some rare cases we may observe skin rash

And minor allergic reactions may also occur infrequently there may be minor altercations in the leukocyte count but these are generally transient now hemolytic anemia and methymoglobinemia are very rare adverse events now hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made but this destruction of red blood cells is

Called hemolysis now as regular cells carry oxygen to all parts of your body so if a patient has a lower than normal amount of red blood cells he may suffer from anemia now on the other hand methemoglobulemia occurs when red blood cells contain methymoglobin at levels higher than one percent now you must be wondering what is methymoglobin well it usually results

From the presence of iron in the ferric form instead of the usual ferrous form and this results in a decrease availability of oxygen to the tissues okay now moving on to the other adrs or adverse reactions remember that renal fibril necrosis is a rare complication of prolonged large dose therapy and as mentioned earlier large dose therapy actually depletes the

Glutathione in the liver now this leaves an acetylene benzoamino benzoaminoquinone to react with the sulfital groups of the hepatic proteins this ultimately leads to hepatic necrosis which is a very serious and potentially life-threatening condition the early symptoms of hepatic damage include nausea vomiting diarrhea and abdominal pain especially patients with

Hepatic disease viral hepatitis or history of alcoholism are at a higher risk of acetaminophen induced hepatotoxicity remember that acetaminophen overdose may be manifested by renal tubular necrosis hypoglycemic coma and also thrombocytopenia now sometimes as a result liver necrosis can occur as well as liver failure the requirement of a liver transplant and

That may also occur now it is important to remember that the toxic effects are not caused by acetaminophen alone but they’re also attributed to an acetyl parabenzo-quinone amine or napqi or napki as it is sometimes sometimes called now this is a toxic metabolite released in the cyp2 e1 pathway so what do we have to do in the case of acetominofin toxicity well

We have to administer an acetylcysteine which contains sulfidel groups to which the toxic metabolite can bind it can be life-saving if it is administered within 10 hours of the overdose but this agent should be avoided in patients with severe hepatic impairment as i’ve been telling you over and over again and the periodic monitoring of liver enzyme tests is also

Recommended for those on high dose acetaminophen okay so this brings us to the end of this lecture we talked about acetaminophen in great detail so next time when you take paracetamol you’ll remember what exactly goes on inside your body for more such videos and for and for more informative lectures keep watching scatty.com so that was all for today remember we

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Transcribed from video
Acetaminophen Pharmacology | Paracetamol Mechanism of Action l Student Lecture By sqadia.com