Muddiest Point: First Pass Metabolism

[@juice28rsx]

I wish you taught at my school!! I have looking for the past hours of videos to describe what you just did, and you did it so simple and clear! subscribing

[@TaiChiKnees]

You are too kind! I'm very pleased the video helped you out.

[@isha5620]

Thank you so much! :) This video cleared my concepts about first pass metabolism quite well!

[@md.rezaulkarim2468]

Finally I get clear concept about first pass effect ... thanks a lot .... subscribing u .. once again thanks :)

[@fsnacj9939]

excellent explanation! very clear

[@DeemahAd]

Great teacher and, IT DOES MAKE A LOT OF SENSE. Thank you :)

[@enochamarh5894]

Thank you for the explanation.

[@natashakakonkanya8710]

Thank you so much great explanation

[@Sukifu99]

excellent explanation ! thank you ✌

[@hitamputih6689]

Very good explanation..I now understand better

[@SAlmutairi1]

Thank you for the great explanation ❤️

[@catherineahonsi4989]

Thank you

[@TaiChiKnees]

Welcome!

[@ammarhamood6445]

your explanation is excellent , thanks alot.

[@TaiChiKnees]

+Ammar Hamood My pleasure!

[@SirPopper]

you saved me. thank you!

[@shaganb1]

Thanks alot

[@suadkacar357]

The best!!

[@xixi2693]

Sir please I have a question When everything exists within nature, whether it is vegetable fruits or allopathic medicine, how the body detects that allopathic medicine is a foreign material ? ? Because allopathic medicine is man made but it from a combination of the matter that exists within the nature so we consider it as natural. Then how the body detects that allopathic is foreign material ?

[@kukkahooka1688]

DEAR MAM THANKYOU FOR THIS SIMPLE AND EASY EXPLANATION BUT I HAVE A DOUBT THAT .. WHY THE DOSE OF PARACETAMOL REMAINS HIGHER(AROUND 1000MG) IN I.V ROUTE ? IT IS EVEN HIGHER THAN THE NORMAL P.O DOSING I.E ABOUT 500-650 MG....? WHY NOT ITS DOSE IS REDUCED IN I.V ROUTE AS IT IS SEEN IN MOST OF THE OTHER DRUGS??

[@Harrem858]

You didn't talk about pro drugs, but they need to be activated by the liver (so can't be given IV), don't they? So first pass metabolism in the case of pro drugs will have more of an activation effect than breakdown effect? Thank you!

[@TaiChiKnees]

You are absolutely right. I don't talk about prodrugs here because I find my students get super confused if I throw that in the mix of the initial lecture. With a prodrug, you NEED the P450 enzymes to activate the drug or it won't work. A famous example is the enzyme CYP2D6's role in activating the pain drug codeine. If you have low levels of CYP2D6, either genetically or because of enzyme inhibition, codeine won't relieve pain effectively. When I was in training, when patients came in and said "codeine doesn't work for me" the assumption was that those patients were just drug seeking for a high and were lying to get a different drug. But no. They weren't lying. They were in pain. At the time, we'd just prescribe a different drug, but in retrospect I still feel bad for suspecting my patients of lying. :-(

[@Harrem858]

Thank you so much! I find pharmacology confusing but your video really helped. Look forward to watching more :)

[@mariahfoley2499]

What about the amount of drug that is absorbed in the small bowel (intestine), wouldn't that decrease the amount that actually goes through the liver? (so not 100% of the drug)

[@TaiChiKnees]

No, ALL the veins from the stomach AND intestines go to the portal vein.

[@mariahfoley2499]

Okay, what about some of the drug being metabolized by GUT and CYPs in the small intestine? would that reduce the dose that reaches the liver since it was metabolized before entering? I guess I meant 100% of the dose going through the liver, would the dose reduce some in the small intestine haha.

[@TaiChiKnees]

The majority of CYP enzymes are found in liver. But even if the metabolizing enzymes were also located in intestine, that would still count as a first pass, right? The important point here is that the dose will have to be higher when giving PO than with other routes of administration. Also, a tip: When you are first learning this stuff, I think it is easiest to separate the 4 processes of pharmacokinetics like this: Absorption will be through Stomach/Intestines if PO Distribution is mostly Bloodstream Metabolism is mostly Liver Excretion is mostly Kidney Of course there are variations and Absorption if topical is through skin, if inhaled is through lungs, etc, but when you are first learning it, keep the various pharmacokinetic processes separate in your head. It will help a lot. I hope this helps.

[@mariahfoley2499]

Yes thank you!