Ionization and Absorption: Intro to Pharm

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Ionization and Absorption: Intro to Pharm

Рет қаралды 65,483

Күн бұрын

Short review of acids vs bases, pH, ionization, weak vs. strong acids, pKa and how all of these things relate to absorption of drugs through the stomach wall. For my Intro to Pharm students, who are predominantly pre-nursing and first-year nursing students. Go to www.boyev.com to get the "First Lecture" handout with the notes for this video.
The direct link is: bit.ly/32wuaQt
-Dr. Boyev
Learning Objectives:
1. Explain the terms "Acid" and "Base"
2. Explain how ionization affects absorption of drugs into tissues or blood
3. Explain why pH tells us the concentration of protons in a solution
4. Explain the terms "strong" and "weak" acid and base.
5. Use the pKa to determine whether a given drug is an "acidic" drug or a "basic" drug.
6. Explain why acidic drugs are well absorbed in the stomach, and understand why antacids change absorption of acidic drugs.
7. Explain how acid/base properties affect the mode of administration, the rate of absorption and excretion.
Answers to Critical Thinking Questions:
1. The antacids that Joe took will increase the pH of the stomach and reduce absorption of the aspirin in the stomach. So the aspirin will take much longer to begin working because less of it will be absorbed in the stomach, the remainder of which will have to be slowly absorbed in the higher pH intestine. Depending on how fast the food goes through Joe, the full dose might not get entirely absorbed.
2. You can increase the absorption of basic drugs like novocaine (or more commonly used septocaine in dentistry) by putting some bicarbonate into the syringe. This makes the drug lipid soluble as it enters the tissues and more likely to penetrate tissues and nerves.
Blame Assessment: Music, Graphics, Info, Cat, Foley: TaiChiKnees.
Excerpt from Ninth Symphony "Ode to Joy" by Ludwig "The Luddster" van Beethoven.
Many thanks to my long-suffering friends... I MEAN... completely random members of the general public... for sending me their FAQ videos.
This video is intended for beginning nursing students. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician with any questions you may have regarding a medical condition. Seriously.

Пікірлер: 62

@lonniethach8065 9 жыл бұрын

This may be intended for nursing students, but this is HELPING me for med school, MANY THANKS!

@rochamancipejuan5280 Жыл бұрын

I loved when you put in spanish. What a good video! Really helps

@Sapphiresash 7 жыл бұрын

This is pure awesomeness! Thank you sooo much

@familymedicine6656 2 жыл бұрын

It is a southern accent and I love it

@sakthiVel-kk7uv 6 жыл бұрын

Nice... Easily understandable

@Mayar10000 9 жыл бұрын

thank you so much for this amazing video !

@gokulpaidi 8 жыл бұрын

thanks a lot mam...it helped me to understand very well u made it really simple...

@harrywoody1024 7 жыл бұрын

Well thought out and put together. If I were giving out a grade, I would give it a A.

@gunjan_rana 7 жыл бұрын

great explanation helped me alot ... thank u soo much

@supernovachampions 7 жыл бұрын

this was extremely helpful! can you clarify, once the ionized ASA (8000x) and deionized ASA are in the blood, which form is readily used at the receptor site? is it the deionized that is easily absorbed thru cells? thanks for clarifying!

@TaiChiKnees 7 жыл бұрын

Great questions: 1. Aspirin is an odd example as drugs go, as it doesn't act by binding a receptor per se; it forms a bond in the active site of the cyclo-oxygenase (COX) enzyme so that the enzyme's normal substrate can't bind. In terms of ionization/deionization, the site of action of aspirin differs depending on the therapeutic effect you are talking about. If it is pain or inflammation, you want it to inhibit the cyclooxygenase enzymes at the site of injury; if you want it to reduce fever, then the target tissue is the brain and if you are interested in the anticoagulant effect of aspirin then you want to target platelets. 2. A deionized molecule moves more easily through fats and cell membranes if it is deionized. An ionized molecule moves more easily through water. So if the target site is inside of a cell it will be helpful if the molecule can get through the cell membrane. If the target site is sitting on the surface of the cell then floating around in the intracellular fluid will be fine.

@vanessah5581 8 жыл бұрын

Thank you for this video!

@Marlencheeen 5 жыл бұрын

very good video! Helped me

@sitizuhairahzainuddin456 5 жыл бұрын

Very helpful!

@ayahere5105 6 жыл бұрын

Great it helped me alt in my study

@daphie92 9 жыл бұрын

Hey, I hope this doesn't sound silly. I am a lil confuse as to why we should administer a conjugate acid of the basic drug orally instead. Please help? Many thanks!

@TaiChiKnees 9 жыл бұрын

Daphne Ng Yeah, sorry, I cut some stuff out of this video for time and it ended up confusing. The point is that you want to have a non-charged (deionized) molecule when you are in the stomach so that it is lipophilic and more easily absorbed. It depends on the base in question in some situations. In the example I have here, the -NH3+ conjugate acid is charged so that isn't actually helpful in terms of ionization, you are totally right. That being said, you WILL see charged conjugate bases being used in some oral formulations in order to make the drug more water-soluble so that it dissolves in the acidic and watery stomach acid faster. Faster dissolving can sometimes make up for the crappier membrane absorption of the charged version of the drug. Sorry again; this is what happens when I try to rush, and although I can explain later in my classroom, folks who aren't my students can end up confused. Sorry!

@rawanmahdi7299 9 жыл бұрын

Thank you ,it was helpful

@MK-cz2rt 9 жыл бұрын

Im a little confused.so if we use the conjugate acid of the basic drug, it dissociates into the base form (it is a reversible reaction right) in the stomach, forming the neutral base that is lipophilic and crosses the stomach. but then it will enter the blood as neutral base. Since you mentioned that blood is basic, how does this basic drug now become charged again? dont uncharged molecules not dissolve in the blood? or are there enough protons inside the blood bind to them and form the conjugate acid again so it could be dissolved?

@TaiChiKnees 9 жыл бұрын

Neurophilia 17 I think you are considering these molecules as being either lipophilic and ONLY soluble in lipid or being charged and ONLY soluble in water. In fact it is a spectrum and even a charged molecule will cross a lipid membrane, only very slowly and less often. If you are talking about a basic drug, even if you start out with a dry pill made only of conjugate acid, once the pill dissolves in the stomach fluids you will see an equilibrium of both forms. Similarly, mildly lipophilic molecules can exist in the blood stream. Remember most drugs are weak acids or bases, meaning that they dissociate only partially. The other trick is to remember that pH is a logarithmic scale, so a very small change in pH can amount to a very big shift in the ratio of deionized to ionized molecules. Even so, it is not an "all-or-none" process. If I were to re-make this video (which I probably won't as it is meant to serve as only background information for the pharmacokinetics lecture in my class) I would probably not bring up the conjugate acid/base business, as it seems to throw people unnecessarily off. I have two learning objectives I wanted to meet in this video: 1) In low pH, as in the normal stomach, molecules that are charged (like bases) will not be well-absorbed. So they won't get absorbed until they hit the small intestine, where the pH is higher. So there is a delay in absorption and the drug won't start working as quickly. You can take basic drugs orally, but they take longer to work. 2) If you have a drug that is specifically formulated to be well-absorbed in the low pH of the stomach, the pharmacokinetics of that drug will be screwed up if the patient takes drugs that increase stomach pH, like antacids, PPIs or H2-histamine antagonists. I hope that helps. :-)

@novu16 9 жыл бұрын

thanks alot!!!! great video

@pokerater4463 5 жыл бұрын

How does a small change in ph can cause a weak acid or weak base to shift from its protonated to deprotonated form????

@TaiChiKnees 5 жыл бұрын

See 11:58 to see a calculation that shows the mathematical relationship. Remember pH is a log-based system. Every 1 point of pH is actually 10x the amount of protons in solution. Hope that helps! :-)

@khadirahmed2668 7 жыл бұрын

thank you so much it is so helpfull

@TaiChiKnees 7 жыл бұрын

You are very welcome!

@BigRed621 7 жыл бұрын

Hi. This video is great! Can i just make sure I have this correct? In water, a strong acid like HCL will almost completely dissociate. However, a weak acid, like aspirin, will only partially dissociate in water until it hits the stomach where the free protons will make it deionized so it can pass through the membrane into the blood stream? Thanks!

@TaiChiKnees 4 жыл бұрын

You got it!

@mduplooy6763 2 жыл бұрын

Thank you for the amazing video! But I am really stuck as to how the aspirin then crosses the cells of the bladder (because they will me mostly ionised from the blood) because ionised cells cannot cross the cell membranes to be able to get into the bladder to form urine?

@TaiChiKnees 2 жыл бұрын

Hey, great question! Here's the cool part: being in ionized form HELPS molecules get into the urine! That's because ionized molecules are better dissolved in water, rather than lipid. And the way that most molecules in your body get excreted is the following: Blood flows into the kidney and past the functional unit of the kidney called the nephron. There, the blood is strained in the glomerulus, and I mean it is almost literally strained like spaghetti in a spaghetti strainer! All the giant molecules and red and white blood cells stay behind, and everything else goes into the nephron tubule. Then the kidney selectively puts necessary stuff back into the bloodstream and everything else flows out into urine.. including the aspirin. This trick can even be used in cases of aspirin poisoning: You can make the pH bloodstream a TINY bit more basic using something like bicarbonate and that makes even more aspirin turn into ionized form and it is strained and urinated out even more quickly!!! Isn't the body, and chemistry, unexpectedly cool?! I hope that answers your question!

@mduplooy6763 2 жыл бұрын

@@TaiChiKnees Wow! THANK YOU! I honestly did not even expect a reply since this video is quite old. I SO appreciate yoyr effort. Fantastic, that is all cleared up.

@ARMESG1983 8 жыл бұрын

Critical thinking.. The antacid will raise the pH of the stomach, but only slightly. The stomach pH will still be acidic. you should still have more than 50% unionized drug left. Aspirin is a weak acid going into an acidic enviroment. The absorbtion of aspirin will only be slowed slightly by the antacid. Am I correct in thinking this.?

@TaiChiKnees 8 жыл бұрын

+ARMESG1983 I wouldn't say it is a minimal effect. And I'm not sure what you mean by 50%. You know when the two forms are the same via the Henderson-Hasselbach equation and pKa. At pH 3.5, the amount of A- = HA, right? So at pH 3.5 50% is ionized, and 50% is deionized: At 3.5, (3.5 = 3.5 + log(A/HA) -> 0= log(A/HA) -> A-/HA = 1 Okay So let's assume the antacid can get the stomach pH to at least 4.0, since that is the pH at which many heartburn (GERD) patients feel pain when the acid refluxes into the esophagus. pH = 4.0 = 3.5 +log(A-/HA) -> 0.5 = log (A-/HA) -> 3.2 = (A-/HA) So even at this only moderately neutralized pH, now there are 3.2 x as many ionized as deionized aspirin molecules. Remember that at pH 1.5 there was 100 x the deionized form. So a little increase in pH has made a big difference in the ratio of the ionized to deionized forms, basically a 320X change in the ratio. Once the drug moves to the intestine, the pH is more like 7, in which case the ratio of ionized to deionized forms is more like 3000, which translates to a 300,000 difference compared to pH=1.5 So the chances of the acidic drug being absorbed are far better while in the stomach and at normal (low) pH. This is why, from the view of pH alone, antacids can have a major impact on the absorption of acidic drugs. Does that make sense?

@md.shahariaralam739 8 жыл бұрын

thank you very much.....it was no it is very helpfull....

@alanoudalkhalifa2731 6 жыл бұрын

Thank you 💕

@AMERSIDD 6 жыл бұрын

Great stuff bud

@carolinelana5527 8 жыл бұрын

i really dont get it, because you said pH is a measure of protons/hydrogens, so if its a low ph acidic, why is the concentration of protons high..... and vise versa? thanks

@TaiChiKnees 8 жыл бұрын

pH is a logarithmic term which is the negative of the log of proton concentration. So if you imagine that the concentration of protons in a solution is .1, or 1x10 to the power of -1, then pH =1. If the concentration of protons is .0001, or 1x10 to the power of -4, then pH is 4. The pH for concentration 0.00000001 is 8, and so on. So the higher the concentration of protons, then the lower the pH. Does that answer your question?

@carolinelana5527 8 жыл бұрын

Hi, sorry for the late reply, yes it does and thanks so much! i passed! haha

@TaiChiKnees 5 жыл бұрын

Yay!

@mmsb12 9 жыл бұрын

I am confused! At 5:45 it says that aspirin has the lowest pKa but is the weakest acid? I thought the lower the pKa = the stronger the acid? Please help!

@TaiChiKnees 9 жыл бұрын

Manny Singh Remember, whether an acid is weak or strong has to do with how completely it dissociates in solution. a STRONG acid dissociates almost completely, and the pKa would be less than 1. A pKa of 3.5 would be more than 1000 times more weak (remember that pKa is a logarithmic scale) in terms of dissociation and relatively speaking is still considered a weak acid. Does that help?

@mmsb12 9 жыл бұрын

TaiChiKnees Oh, that makes complete sense! Thank you vey much! - One happy Pharmacy undergrad :)

@amalhamdey1547 7 жыл бұрын

at first you said that ph= pka+log [conjugate base ]/ [acid ] and at last ph =pka+log aspirin /aspirin -H but the aspirin is the acid and the aspirin -H is the conjugate base ??? iam confused and in my pharma book it is protonated /unprotonated idonot understand how is the conjugate base the protonated form

@TaiChiKnees 7 жыл бұрын

aspirin-H is the acid because that is the form that has the extra proton that can attach or detach depending on the pH of the solution. aspirin- is the "conjugate base" of aspirin. So "protonated" means the molecule when it has a proton (H+) stuck on the molecule. "unprotonated" is when the molecule is missing that H+. That's a different concept from a molecule being charged/polar/hydrophilic vs a molecule being uncharged/nonpolar/lipophilic Aspirin's molecular formula is CH3COOC6H4COOH. So if we were to write the chemical equation we'd write: CH3COOC6H4COO- + H+ CH3COOC6H4COOH unprotonated protonated So aspirin is a weak acid. That means that when it is protonated (the proton (H+) is attached) it has no charge. If it has no charge it is nonpolar and soluble in fat (lipophilic). From the above equation you can see that the unprotonated form CH3COOC6H4COO- has an overall negative charge. That is the "conjugate base" of aspirin. The original video went more into conjugate acid and base but I cut it out for time, which I think made the whole business a little confusing. In general: If you talk about conjugate forms then the thing to remember is that: For a weak acid, the protonated form is uncharged/nonpolar/fat soluble For a weak base, the protonated form is charged/polar/water soluble. Does that make sense?

@amalhamdey1547 7 жыл бұрын

yes it does thanks alot ^_^ and sorry for the late reply

@amalhamdey1547 7 жыл бұрын

there is another thing i want to ask about .. for absorption the drug should be lipid soluble to cross the plasma membrane but dissolution also is an important process for absorption and it require water solubility and polarity so how this can happen ?? Thanks ^_^

@mbvefjysgf 9 жыл бұрын

really helpful thank you :)

@TaiChiKnees 9 жыл бұрын

I'm so glad! Good luck with your studies!

@fp4201 7 жыл бұрын

I found it very helpful. I wonder what kind of water you recommend to drink since the quality of regular plastic bottles have harmful toxicity of the plastic & pollution and also a low pH(6.0). I found this kangen ionizer water machine which have ionization technology. Also, noticed it's better to drink water recently made by an ionizer machine or literally drink fiji water at fiji islands since the h+ after a while will oxidate or have less conductivity? Like making cold press juice, it will decay and start oxidation. What do you think about any bulk or trace minerals should be add to the solution? Thanksss

@TaiChiKnees 7 жыл бұрын

If you've got a sensitivity to chemicals and environmental triggers then I would confer with your health care provider. If not, then I'll say this: The problem with the premise that we need to worry about toxicity in plastic bottles or trace elements in tap water is that it presupposes that there are safe things in our environment. There aren't. Everything, in high enough concentration is toxic. Including oxygen and pure glacial water. (Seriously, google oxygen toxicity and hyponatremia. Even water and oxygen are bad for you.) And of course the vast majority of vitamins and supplements sold in the US don't actually contain what the label says they contain. (Google "USP" to find trustworthy supplement companies and google "New York class action suit against GNC, Walmart, Walgreens and Target"). So what can you do if everything is potentially toxic? You just live your life and disregard any website or spokesman (like Dr Oz) that claims to be selling something that is safe or protects you against common environmental problems. As for what minerals to add to your water: Answer: None. Eat a balanced diet. You'll be fine. If you're a vegan, be sure to buy trustworthy B12 replacement. Go on with your life. Everything is okay.

@abdullahbineid4963 7 жыл бұрын

BIG LIKE

@mayurishangout5876 6 жыл бұрын

Thnq

@08060915 9 жыл бұрын

whats the music at the calculation part? its nice haha

@TaiChiKnees 9 жыл бұрын

natsunokirihime Thank you for the compliment. That's just some music I wrote for a composition class homework assignment a few years ago and it was the right length. :-)

@shrikantmalpani3396 6 жыл бұрын

Good

@hatemmohamed9489 6 жыл бұрын

i love u now :D

@louiethemouseful 8 жыл бұрын

I thought low Pkas were strong acids and higher Pkas were strong bases

@TaiChiKnees 8 жыл бұрын

+louiethemouseful Yes? But we are talking about drugs in the human body, right? A "strong acid" is one that will completely dissociate in solvent; in humans the solvent is water. for instance HCl, in your stomach, is a strong acid. So if you have HCl in water, it is almost completely H+ and Cl- and not the combined form. In fact the pKa of HCl is so low that it is less than zero. (Review the definition of pKa and be sure you understand how logarithms work). But generally speaking, "strong" acids and bases are irrelevant to a discussion of drugs, because almost all medically useful drugs are weak acids or weak bases, meaning they only partially dissociate at physiological pH in the bicarb buffer. Except for in the stomach, the pH in our body is around 7.4-ish, which is pretty close to the pH of plain water (7). ...maybe I'm not understanding your question? I guess I don't understand the relevance? We aren't talking about strong acids...

@jmitroka 4 жыл бұрын

Interesting but wrong. Drugs are not absorbed from the stomach. They are absorbed in the small intestine. The reason drugs that are weak acids and basesare absorbed in the intestine is that some fraction of drug is always in the uncharged state and available to move across the intestine into the blood.

@TaiChiKnees 4 жыл бұрын

I'm sorry, but you are not correct about about that. Drugs that are uncharged at low pH are definitely absorbed through the stomach wall. We take advantage of this with some medications like aspirin because that allows them to be very fast acting. (You probably know that alcohol is also absorbed in the stomach because it is lipid soluble. Any drug that is lipid soluble will pass through cell membranes.) You are correct, however, that the majority of absorption of both drugs and nutrients takes place in the intestine because of the vastly increased surface area there. Please take a look at the calculations at the end of the video to see the vast difference in percent ionization that pH makes. Also consider the differences in transit times between individuals. Thank you for your question; I'm sure other students had it as well.

@jmitroka 4 жыл бұрын

@@TaiChiKnees From the Merck Manual - Professional Edition. "The small intestine has the largest surface area for drug absorption in the GI tract, and its membranes are more permeable than those in the stomach. For these reasons, most drugs are absorbed primarily in the small intestine, and acids, despite their ability as un-ionized drugs to readily cross membranes, are absorbed faster in the intestine than in the stomach."