In pharmacology it is one of the commonly asked questions….

Q. Explain why Indomethacin is used in children with Patent Ductus Arteriosus ?

Answer- you can get direct answer of this question from any book of Pharmacology you read….

But lets take this opportunity to develop our understanding about the disease and the drug. first we will understand what is Patent Ductus arteriosus……

Patent Ductus arteriosus-

First of all, we as Medical Students, knows very well that Pulmonary artery carries blood from right heart to the lungs.

And The Aorta carries blood from heart to the body…. … in foetus, ductus arteriosus is an extra blood vessel or you can say connection (Which is normal by the way in foetus) that connects The Pulmonary artery to the Aorta…….because before birth the lungs of the foetus are not activated and the foetus gets oxygen from the mother.

Do you know, that all newborns have this opening intact during birth and it closes on its own, as the baby starts breathing and lungs take charge of proving oxygenated blood.

But rarely, if it stays open, this condition is termed as Patent Ductus Arteriosus. (Comparatively more in premature infants)

We know that the right heart pumps blood to the lung and left heart to the body, here the blood from the left heart is pumped to the lungs also, which cause extra pressure on the lungs, this makes the heart and lung work harder and lungs can become congested.

Now How Indomethacin can be useful in Medical treatment of Patent Ductus Arteriosus?

Normally, the Patency of Ductus Arteriosus is due to the Prostaglandins (due to continuous secretions of PGE2 and PGI2)

And we know that Indomethacin is a NSAID (Non steroidal Anti-inflammatory Drugs) which exert their effects by Prostaglandin synthesis inhibition.

Indomethacin is a highly potent inhibitor of PG synthesis and when Indomethacin is given as IV injections 12 hourly three times at dose of 0.1 to 0.2 mg/kg, it achieves closure of PDA in majority of cases.

Hope you understand the concept and enjoyed the post…….

Happy learning……..

Well, in series of clearing our concepts…. lets take a look on a very favourite question of Examiners in Pharmacology…….

Q. Explain why Allopurinol is used in chronic Gout? or

Q. Explain why we don’t use Allopurinol in Acute Gout?

So, Acute gout is sudden, severe inflammation in joint where the joint become red, swollen and Extremely painful, i hope you remember that the Great Toe (specifically metatarso-phalangeal joint) is commonly involved.

and we also know, that gout is considered as metabolic disease, in which, there is HYPERURICAEMIA (Increased uric acid in blood, compared to normal values which is 2-6 mg/dl) . But in acute gout (let me remind you red, swollen, painful great toe) we need immediate treatment to make patient feel normal.

So, we give

1. NSAIDs (Non Steroidal Anti-inflammatory Drugs) – like Diclofenac, Indomethacin or Etoricoxib, in Relatively high and repeated doses (We have to control a painful situation)

2. Colchicine -though response is dramatic, but due to its higher toxicity NSAIDs are preferred now a days

3. Corticosteroids– Intraarticular injection of triamcinolone is preferred and as usual, we go to steroids when NSAIDs/Colchicine did not work or not tolerated. rarely we go for systemic steroids.

And now i can sense, someone hitting his head hard on the wall “you are supposed to tell us about why we use Allopurinol in chronic gout and not in the acute gout”?

Yes, you are right, but here i am trying to make a point that in acute gout the target is to control the painful inflammatory condition, not the level of uric acid.

And as you may know, Allopurinol is a drug which decreases the uric acid level as it is uric acid synthesis inhibitor (act by inhibiting “Xanthine Oxidase”, the famous enzyme responsible for synthesis of uric acid).

And Allopurinol is the first choice drug in Chronic Gout.

But the Allopurinol also should not be started during an acute attack, because as the uric acid level decreases, there are chances of shedding of urate crystals from articular cartilage into joint space and this can initiate or worsen an acute attack.

So, 1. Do Not starting allopurinol during Acute attack of gout

2. Start Allopurinol with NSAIDs initially, to prevent an acute attack, till uric acid level stabilizes.

Hope you enjoyed the concept…..

Happy learning………

Q. Name the drug of choice in acute Paracetamol Poisoning ?

Q. Role of N- Acetyl Cysteine in acute Paracetamol Poisoning ?

Now, to understand this better, we start with …………

Acute Paracetamol Poisoning – when anyone consumes a large dose (10 gm or more in adult) of paracetamol suddenly (within 24 hour time duration), it is a medical emergency and termed as acute paracetamol poisoning.

The patient usually comes to you with Liver tenderness, nausea, vomiting, abdominal pain and later on, sometime after day or two or three (depends on how massive the dose is) hepatic necrosis, renal necrosis and hypoglycemia occur and if untreated, then coma and death.

In short, we can say that, if more then 150 mg/kg as per body weight paracetamol is taken, then it produces serious toxicity and more then 250 mg/kg is usually fatal.

But the good news is that if N- Acetylcysteine is given to the patient within eight hours of acute Paracetamol poisoning then Hepatotoxicity is extremely rare (It is claimed to be 100 % effective if given within 8 hours, however if there is delay in starting treatment with N-Acetylcysteine, then as the time increases, the worst will be the outcome).

You can say, we use N- Acetylcysteine for Acetaminophen (Its another name for Paracetamol) Poisoning. remembering this by heart and it will help in your theory, viva and in real life emergency situation, as Paracetamol is one of the most common, over the counter drug available all over, hence overconsumption cases are not uncommon.

But why N- Acetylcysteine is used ? ………

well, lets dive deeper……when we take PCM then it metabolizes in Liver…..

During metabolism 1) it undergoes glucuronidation and sulfation mostly (do you remember that during metabolism there were Phase II reactions by which our body attach the water soluble substances like glucuronic acid etc. to the drug and make the drug water soluble, suitable to be execrated by urine)

2. Very small amount (nearly 5%) metabolized by P-450 dependent hydroxylation and after this an Highly reactive compound NAPQI (N-Acetyl-P-Benzoquine imine) is formed and it also further goes into glutathione conjugation and then execrated in urine.

One more point i want to add here that glutathione is a major antioxidant, protect our body from free radical injury.

When PCM is taken in excessive amount then there is excess NAPQI , Glutathione cannot meet with this sudden increased demand to neutralize NAPQI and there is Glutathione depletion in the liver.

Now in our body, there is NAPQI in excess and no glutathione to protect our liver from this highly reactive compound. At last, excess NAPQI binds to the cellular macromolecules and causes hepatic necrosis , renal necrosis etc.

And what changes, when we provide N- Acetylcysteine, well it act by….

1. It Replenish the Glutathione stores in the liver (N-Acetylcysteine is a glutathione precursor, and Glutathione is naturally occurring antioxidant produced in liver)
2. It binds with NAPQI (Yes, the reactive metabolite) and thus prevents it harmful effects.
3. It protect against extrahepatic injury due to its antioxidant and anti-inflammatory properties.

If you want to know the dose and the route…….

150 mg/kg by i.v. route (In 200 ml 5% glucose) over 20 minutes repeated again after 20 hours.

Here are some interesting facts, that Alcoholism, malnutrition , Cancers are some other conditions which are usually associated with glutathione deficiency and no wonder, in chronic alcoholics the fatal dose of PCM can be reduced to 5 grams.

And in children below six years you rarely see PCM toxicity because the PCM syrups/drops are provided in a limited dose and also the metabolism is dominated by the sulfation. (But taking very high doses eg. PCM tablets can lead to severe liver and renal damage)

Hope you enjoyed the concept…..

Happy learning……will back to you soon …..