I have a question. How could you say the drug needs to be unionised to pass through the lipid membrane at 2:08 but then say ionised means soluble at 5:45?
There's an important distinction between "solubility" and "lipophilicity (i.e. ability to pass through the lipid membrane [lipophilicity can also be thought of as solubility in lipids])." The difference between the two is explained between 1:45-2:13. Basically, "solubility" is a general term that refers to a drug/molecule's ability to solubilize (i.e. dissociate/break down and dissolve into a given solution), which is dependent on ionization as she explains. Solubility/ionization are dependent on three solubility factors: 1. Acid/base profile of the drug (is drug an acid or a base?) 2. pKa of the drug (IF drug is an acid, is pH > pKa to allow ionization/dissociation? IF drug is a base, is pH < pKa to allow ionization/dissociation?) 3. pH of the solution/environment For a drug to be in its ionized (dissociated/broken down) form, it should be in a pH that is favorable to its acid/base profile, and also favorable to its pKa, as detailed above. This is the A=A, B=B concept she explains at 5:35. The summary graph at 8:36 is a helpful visual representation of this. Example 1: Drug Z is a weak *base* and has a *pKa of 6.* In stomach acid (pH ~2), *pH < pKa,* which is a *favorable* condition for a *base* to ionize/solubilize, thus Drug Z is *soluble* in *stomach acid.* However, if Drug Z is in the blood (pH ~7.4), *pH > pKa,* which is an *unfavorable* condition for a *base* to ionize/solubilize. Therefore, in the *blood*, Drug Z would remain *un-ionized*/insolubilized, and therefore be *insoluble.* Example 2: Drug Q is a weak *acid* and has a *pKa of 4.* In stomach acid (pH ~2), *pH < pKa,* which is an *unfavorable* condition for an *acid* to ionize/solubilize, thus Drug Q is *insoluble* in *stomach acid.* However, if Drug Q is in the blood (pH ~7.4), *pH > pKa,* which is a *favorable* condition for an *acid* to ionize/solubilize. Therefore, in the *blood,* Drug Q would ionize/solubilize and therefore be *soluble.* Separately, to determine lipophilicity (ability to pass through lipid membrane) we look at one factor: 1: Ionization/charge/polarity of the drug/molecule (yes, 3 different things, but if you know one, then you immediately know all 3 [i.e. an *ionized* molecule holds a *charge* (as opposed to being neutral), thus it is *polar*] As we've been taught in biochemistry, "likes dissolve likes," meaning polar substances dissolve in polar substances, and non-polar substances dissolve in non-polar substances. Lipids are non-polar, so a substance must be non-polar (un-ionized/uncharged) to pass through. Example 1: If Drug Z is *ionized,* it holds a *charge,* and is therefore *polar.* Drug Z therefore *CANNOT* cross the *non-polar lipid membrane.* Example 2: If Drug Q is *un-ionized,* it does *not hold a charge,* and is therefore *non-polar* (unless indicated otherwise). Drug Q therefore *CAN* cross the *non-polar lipid membrane.* Hope this helps!
So by solubility she means water soluble , if the drug is hydrophilic thn it's ionised so it's soluble If the drug is lipophilic means unionised thn it's not soluble in water
@@flatulate181 then why is that we always keep enhancing the solubility of the drug, if the drug is as such insoluble in water, there is lot of chance that API remains undissolved , which according the explanation it's unionised and more likely to get absorbed into lipid membranes....
As we know only unionised form of drug is going to absorb through lippophilic cell membrane at 6:57 you cleared for weak base craitaria for drug to be soluble is its pH should be less than pka then its going to be ionized in stomach more then 50% lower the pH more drug will ionize that is 90% and only 10% would be unionised so how come maximum absorption of drug in intestine will take place as unionised form of drug is very less..... I don't understand our approach should be more availability of unionised form of drug rather ionized form. I don't understand weak acid ph>pka and for weak base ph
was thinking the same. If the pKa is higher, it should mean that according to these principles it should be below base. Which makes it soluble, which means its in its ionised form and when its in its ionised form it cannot be classified as absorbed as the majority of it is not absorbed. ionised molecules cannot cross the cell membrane.
Is there a mistake at 5:36 ? Correct me if im wrong but, did she switch the unionized side with the ionized one??? Anyways thanks for the video! As a dental student pharmacology is not discused in such detail
I can't seem to understand this, if we have a medicine with a pKa of 9. Wouldn't it need a pH ABOVE 9 to be absorbed across the membrane and carried to the blood? We don't have a pKa in the GI of 9, does it mean that such medicines can not be taken by the oral root? But then even if it's administred directly in the blood, the blood has a pH of 7, this will still cause the medicine to become ionized, can it still be delivered to the place of action?
In the pharmaceutical/pharmacology industry there are many techniques used to deal with these issues. We cannot control what the body does, as it is nature, therefore we must use technology when making drugs to deal with this. Drugs need to be ionized to become soluble, but in their ionized state they cannot partition into the blood through the GI tract wall. Most drugs in the pharma industry are hydrophobic i.e non polar and so are not good at dissolving, therefore we use formulations, peptides and other solubility cloaking technology to deal with this. We usually don't worry about how to make a polar drug partition through the GI tract wall, it is usually solubility of non polar we care about. Hope this cleared stuff up, even 4 months down the line. If anyone spots any alterations this could use, please don't hesitate to correct me!
when the aspinrin is in the stomach;it has mor fat soluble form(unionised) .wich easly passes throught the membranes and then once it is in a mor basic solution become water soluble (ionises)and has delevery
@@jenaabhijit when the aspinrin is in the stomach;it has mor fat soluble form(unionised) .wich easly passes throught the membranes and then once it is in a mor basic solution become water soluble (ionises)and has delevery
you make a mistake in the example of the basic drugs . when you said that at ph 7 the equation will shift more to ionized form (no it will shift to the unionized form)
Sorry, she's right. For a basic drug, if pH < pKa (pH=7, pKa=8), this is a favorable condition for the basic drug to ionize (since it is a base in more acidic conditions), therefore it will go to its ionized form. Different approach than her Lechatelier's explanation, but still holds true. Conversely (also with a basic drug), if pH > pKa (pH=9, pKa=8), this is an unfavorable condition for the basic drug to ionize (since it is a base in further basic conditions), therefore it will remain and/or shift to its un-ionized form.
After watching a dozen of videos on UA-cam, topic is finally cleared.
yeah husna
As a P1, this was great information for getting the "big picture" concept for pharmaceutics!! Thanks!!
You organized this in such an easy-to-follow way - it is obvious you know your stuff! Thank you :) :) :)
Excellent, simply out of word. She is brilliant.
How are you not popular yet? We need more people like you
she don't used to upload dt is why,but she is realy good tutor, i just subbed to her cuz i don't want to missed her update.
Very helpful video when reviewing for the NAPLEX. Thanks!!
Thanks a lot for your efforts...really the method you used and the way you explained the topic with was very nice....thanks again and keep it up👍
Informative 🔥🔥
Thanks! I'm in med school and was confused, this helps a lot!!
Great job, the best video about pKa. very simple and neat explanation. But there are few mistakes. Would be thankful if you revise and correct them.
I have a question. How could you say the drug needs to be unionised to pass through the lipid membrane at 2:08 but then say ionised means soluble at 5:45?
There's an important distinction between "solubility" and "lipophilicity (i.e. ability to pass through the lipid membrane [lipophilicity can also be thought of as solubility in lipids])."
The difference between the two is explained between 1:45-2:13.
Basically, "solubility" is a general term that refers to a drug/molecule's ability to solubilize (i.e. dissociate/break down and dissolve into a given solution), which is dependent on ionization as she explains. Solubility/ionization are dependent on three solubility factors:
1. Acid/base profile of the drug (is drug an acid or a base?)
2. pKa of the drug (IF drug is an acid, is pH > pKa to allow ionization/dissociation? IF drug is a base, is pH < pKa to allow ionization/dissociation?)
3. pH of the solution/environment
For a drug to be in its ionized (dissociated/broken down) form, it should be in a pH that is favorable to its acid/base profile, and also favorable to its pKa, as detailed above. This is the A=A, B=B concept she explains at 5:35. The summary graph at 8:36 is a helpful visual representation of this.
Example 1: Drug Z is a weak *base* and has a *pKa of 6.* In stomach acid (pH ~2), *pH < pKa,* which is a *favorable* condition for a *base* to ionize/solubilize, thus Drug Z is *soluble* in *stomach acid.* However, if Drug Z is in the blood (pH ~7.4), *pH > pKa,* which is an *unfavorable* condition for a *base* to ionize/solubilize. Therefore, in the *blood*, Drug Z would remain *un-ionized*/insolubilized, and therefore be *insoluble.*
Example 2: Drug Q is a weak *acid* and has a *pKa of 4.* In stomach acid (pH ~2), *pH < pKa,* which is an *unfavorable* condition for an *acid* to ionize/solubilize, thus Drug Q is *insoluble* in *stomach acid.* However, if Drug Q is in the blood (pH ~7.4), *pH > pKa,* which is a *favorable* condition for an *acid* to ionize/solubilize. Therefore, in the *blood,* Drug Q would ionize/solubilize and therefore be *soluble.*
Separately, to determine lipophilicity (ability to pass through lipid membrane) we look at one factor:
1: Ionization/charge/polarity of the drug/molecule (yes, 3 different things, but if you know one, then you immediately know all 3 [i.e. an *ionized* molecule holds a *charge* (as opposed to being neutral), thus it is *polar*]
As we've been taught in biochemistry, "likes dissolve likes," meaning polar substances dissolve in polar substances, and non-polar substances dissolve in non-polar substances. Lipids are non-polar, so a substance must be non-polar (un-ionized/uncharged) to pass through.
Example 1: If Drug Z is *ionized,* it holds a *charge,* and is therefore *polar.* Drug Z therefore *CANNOT* cross the *non-polar lipid membrane.*
Example 2: If Drug Q is *un-ionized,* it does *not hold a charge,* and is therefore *non-polar* (unless indicated otherwise). Drug Q therefore *CAN* cross the *non-polar lipid membrane.*
Hope this helps!
@@flatulate181 i can't love u less dear, pls where are u from,thank u for ur efforts once again.
So by solubility she means water soluble , if the drug is hydrophilic thn it's ionised so it's soluble
If the drug is lipophilic means unionised thn it's not soluble in water
@@flatulate181 then why is that we always keep enhancing the solubility of the drug, if the drug is as such insoluble in water, there is lot of chance that API remains undissolved , which according the explanation it's unionised and more likely to get absorbed into lipid membranes....
Very well simplified! Thanks for the amazing video
Best explanation.thanks a lotttt
You clear all my doubt . It was really a helpfull video.....🙏🖤
This is the best video for pk and ph thx 💙
fantastic
brillint!!!!!!!!!!!!!!!!!!!!!!!!!! so much love and respect keep it up you are great:)
Very very helpful video. Exact thing I was looking for.
very helpful vdeo...TY
I've found in a couple of sources that paracetamol is a weak acid, why do you say it is basic?
great video. thanks for making it so simple
amazing and very informative video!
informative video👍keep it up
LOVED this video thank you!
As we know only unionised form of drug is going to absorb through lippophilic cell membrane at 6:57 you cleared for weak base craitaria for drug to be soluble is its pH should be less than pka then its going to be ionized in stomach more then 50% lower the pH more drug will ionize that is 90% and only 10% would be unionised so how come maximum absorption of drug in intestine will take place as unionised form of drug is very less..... I don't understand our approach should be more availability of unionised form of drug rather ionized form. I don't understand weak acid ph>pka and for weak base ph
Are working with Osmosis channel ? Ur style is so similar btw great explanation
Thank you
Finally,y nailed it
ALHAMED LEALLLAH I got it
Wait, but, the PH of intistene is 8 as you said how is parecetemol absorbed when it's pka is higher?
was thinking the same. If the pKa is higher, it should mean that according to these principles it should be below base. Which makes it soluble, which means its in its ionised form and when its in its ionised form it cannot be classified as absorbed as the majority of it is not absorbed. ionised molecules cannot cross the cell membrane.
@@nusrahdavids2407 I was thinking she was saying things backwards as well. Made me even more confused.
Is there a mistake at 5:36 ? Correct me if im wrong but, did she switch the unionized side with the ionized one???
Anyways thanks for the video! As a dental student pharmacology is not discused in such detail
mary syeg I think you are right
@@alkorbaa84 i agree
Noo
What if the body has acid-base imbalances??
Very helpful video!!! thanks.
I av nt understood well for the case of weak basic drugs....😕
Very very very very Greaaaaaat !!!!!!😀😀
I can't seem to understand this, if we have a medicine with a pKa of 9. Wouldn't it need a pH ABOVE 9 to be absorbed across the membrane and carried to the blood? We don't have a pKa in the GI of 9, does it mean that such medicines can not be taken by the oral root? But then even if it's administred directly in the blood, the blood has a pH of 7, this will still cause the medicine to become ionized, can it still be delivered to the place of action?
In the pharmaceutical/pharmacology industry there are many techniques used to deal with these issues. We cannot control what the body does, as it is nature, therefore we must use technology when making drugs to deal with this. Drugs need to be ionized to become soluble, but in their ionized state they cannot partition into the blood through the GI tract wall. Most drugs in the pharma industry are hydrophobic i.e non polar and so are not good at dissolving, therefore we use formulations, peptides and other solubility cloaking technology to deal with this. We usually don't worry about how to make a polar drug partition through the GI tract wall, it is usually solubility of non polar we care about.
Hope this cleared stuff up, even 4 months down the line. If anyone spots any alterations this could use, please don't hesitate to correct me!
What app do u use?
very nicely explained.Thank you.
So the Pka is higher than the ph when the drug is acidic ? and vis versa ?
Thank you so much
What writing app are you using?
Finally got the answer❤❤❤
Thank you very much
What app you Used ?
Very clear!!!
Thanks 👍
thank u so much bab 💓💓😍
Madam one thing is remaing that is if acidic drug is unionised in stomach means that it is insoluble in stomach and how insoluble drug absorb?
Right..... Could u find the answer?????
when the aspinrin is in the stomach;it has mor fat soluble form(unionised) .wich easly passes throught the membranes and then once it is in a mor basic solution become water soluble (ionises)and has delevery
@@jenaabhijit
when the aspinrin is in the stomach;it has mor fat soluble form(unionised) .wich easly passes throught the membranes and then once it is in a mor basic solution become water soluble (ionises)and has delevery
❤❤❤❤❤❤❤❤
thank you
you make a mistake in the example of the basic drugs . when you said that at ph 7 the equation will shift more to ionized form (no it will shift to the unionized form)
Not so. Make a base more neutral and it becomes more soluble.
Sorry, she's right. For a basic drug, if pH < pKa (pH=7, pKa=8), this is a favorable condition for the basic drug to ionize (since it is a base in more acidic conditions), therefore it will go to its ionized form. Different approach than her Lechatelier's explanation, but still holds true.
Conversely (also with a basic drug), if pH > pKa (pH=9, pKa=8), this is an unfavorable condition for the basic drug to ionize (since it is a base in further basic conditions), therefore it will remain and/or shift to its un-ionized form.
not log, you must say lg
😍😍😍😍😍😍
I believe you need to review your information. I think you are incorrect on several parts.
3:56 99% Ionised and 1% Unionised
No 99% unionised and 1% ionised
What she said is right
Not satisfied🙄🙄
hahhh
400th like
informative video👍keep it up