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Drug Metabolism Made Simple *ANIMATED*

Оценок: 614 | Просмотров: 41997
metabolism is the protective biochemical process by which our bodies alter xenobiotics either enzymatically or nonenzymatically. generally, drug metabolism begins with hydrophobic drug and converts it to a more hydrophilic metabolite to facilitate its elimination. an understanding of the drug metabolism process and the potential outcomes is critical for developing safe and useful pharmaceuticals. drug metabolism can result in one of two products, an inactive metabolite and an active metabolite. inactive metabolites of the drugs basically have no pharmacological activity of the original drug. an example of that would be the hydrolysis of procaine into para aminobenzoic acid and diethylethanolamine which results in the loss of the anesthetic activity of procaine. on the other hand, an active metabolite can mean that a metabolite can retain the same activity of the parent drug, that's apparent when codeine is demthylated to a more active drug which is morphine. however, in some cases we notice a result known as bioactivation where the parent drug is inactive and the metabolite would have a pharmacological activity, in this case the inactive parent drug is called a prodrug. an example of a prodrug is enalapril which has no activity as an antihypertensive, but upon hydrolysis it becomes enalaprilat which is a potent antihypertensive drug. bioactivation of a drug can also lead to toxic metabolites, the widely used acetaminophen has a metabolite that is called n-acetyl-p-benzoquinone imine which is hepatoxic, I explained the mechanism of the toxicity and the antidote in my previous video which I linked in the description below. The liver has the highest concentration of drug-metabolizing enzymes, because of it’s location between the gastrointestinal tract and the systemic circulation. Based on the reactions involved in the metabolism process we can classify the metabolic pathways into phase I metabolism and phase II. Phase I metabolism is characterized as a functionalization reaction, where they add or reveal a functional group by oxidation, reduction, or hydrolysis, hence, leading to increase in overall polarity of the drug which facilitates its excretion in the urine Oxidation is the most common phase I reaction, Cytochrome p450 is a superfamily of oxidases that are responsible for the majority of oxidation reactions, it’s found in very high concentrations in the liver. Oxidation can also happen through alcohol dehydrogenase which is an enzyme that oxidizes alcohols into aldehydes from primary alcohols and to ketones from secondary. Aldehydes can be oxidized from to carboxylic acid by the enzyme aldehyde dehydrogenase. We can see that in the example of the conversion of acetaldehyde to acetic acid in the metabolism of ethanol. Another phase I reaction is the reduction reaction, there are several reductase enzymes common reduction reactions include the reduction of disulfide bonds, in which the disulfides would be reduced to free sulfhydryls. Another reduction reaction is done by the aldo-keto reductases which reduce carbonyl containing compounds back to alcohol in a process opposite to the oxidation done by alcohol dehydrogenase. The last type of phase I metabolism reaction is hydrolysis, hydrolysis is basically the addition of water across a bond resulting in a more water-soluble metabolite. A great example of hydrolysis is ester hydrolysis which is performed by the enzyme esterase found throughout the body, esterase is responsible for the hydrolysis of an ester into a more soluble alcohol or carboxylic acid. Phase II Phase II reactions are commonly called conjugation reaction owing to the fact they add a functional group on the drug for the purpose of increasing its polarity. The conjugation process requires an enzyme generally termed as transferase, that transfers the large polar molecule called a co-factor onto the drug, Examples of phase II reactions: glucuronidation is the most common phase II reaction, glucuronosyltransferase is the enzyme that uses UDP-GA as the cofactor to transfer glucuronic acid to several functional groups like hydroxyl groups, carboxylic acid ,and hydroxylamines. The glucuronic acid adds a significant amount of hydrophilicity to the molecules facilitating it’s excretion process. Another popular reaction is glutathione conjugation which results from the addition of glutathione molecule to an electrophilic substrate. Being a nucleophile glutathione generally acts to detoxify electrophiles. Glutathione-s-transferase is the enzyme responsible for the reaction of glutathione with electrophiles like epoxides and halides. After the conjugation, the product is excreted as mercapturic acid in the urine. Paracetamol antidote video: https://www.youtube.com/watch?v=hg_gpWjWsRM
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Текстовые комментарии (34)
Metabolic Health (8 дней назад)
https://www.youtube.com/watch?v=upuxsbN6p-M https://themetabolichealth.com
Abhineet Dey (9 дней назад)
Great job!
i lovecars (13 дней назад)
u guys are fuckers the pharma and the years you study is to kill and ruin someones life
Sreetama Roy (19 дней назад)
Thanks a lot for making me understand a concept that I struggled with throughout my 5 years of med school...Finally!
Pill Whiteboard (18 дней назад)
Most welcomed, my pleasure.
Neelam Sharma (1 месяц назад)
tnq so much sir 😊...
Pill Whiteboard (1 месяц назад)
My pleasure
Onyapidi (1 месяц назад)
Very well explained, thank you
Rahul P (3 месяца назад)
To improve your videos even further.. please check the spelling in your animation. It's very distracting when there is a spelling error. Great job doing the video though
Pill Whiteboard (3 месяца назад)
I will, thank you for your feedback
Aditya Solanki (4 месяца назад)
Very helpfull thkyou sir
Anjali Malik (4 месяца назад)
Very helpful Thank you
drrop (4 месяца назад)
Thanks million times...sir
AnotherBadyoga (5 месяцев назад)
thanks so much for this
Estefania Zarate (5 месяцев назад)
Amazing! Thank you!
coal cactus (6 месяцев назад)
awesome ......very helpful video please make more alike videos
Madiha Waqar (6 месяцев назад)
well explained ..... thank you sir
Pill Whiteboard (6 месяцев назад)
You're most welcomed
Jdoedely Ewing (6 месяцев назад)
I don't know how to thank this explain so well, great job.
Pill Whiteboard (6 месяцев назад)
You're most welcomed
Dr Sarfraz Baloch (6 месяцев назад)
So the what's function of cytochrome p450 in metabolism?
Dr Sarfraz Baloch (6 месяцев назад)
Okay but please some describe CYP450
Pill Whiteboard (6 месяцев назад)
It's the enzyme that facilitates the oxidation of molecules resulting in easier excretion
Edward Tobe (8 месяцев назад)
This is a very condensed but valuable explanation. The author's style captures attention. Compare the written script with the animated presentation and for me, the animated presentation enable the script. The effort and time to create this presentation was not humble.
Pill Whiteboard (8 месяцев назад)
+Edward Tobe wow, you sir humble me with your praise. thanks alot, comments like this push me foreward.
iam lone (9 месяцев назад)
Pill Whiteboard (9 месяцев назад)
+Waqar Ahmad Lone glad to hear that
Natan Glauber filippi (9 месяцев назад)
At 5:22, you spelled easter, but it should be ester
Pill Whiteboard (9 месяцев назад)
+Natan Glauber filippi thank you for noticing
Vishwa patel (10 месяцев назад)
Can u make videos on Drugs acting on automic nervous system?
ProfGuyFoxx (9 месяцев назад)
Vishwa pate
Pill Whiteboard (10 месяцев назад)
+Vishwa patel I will soon
Vishwa patel (10 месяцев назад)
Very good explanation....keep it up
Pill Whiteboard (10 месяцев назад)
+Vishwa patel thank you so much , I will

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