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NBME 20 Answers

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submitted by โˆ—hayayah(1212)
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In order for a drug to be cleared by the kidney, it must first be filtered in the glomeruli. Drugs with a high VD have more of the drug in the tissue that are not available to filtered by the kidney. Drugs with high protein binding won't be filtered either. So you want a drug with low Vd and low binding if you want it cleared via the kidneys and urine.

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zevvyt  But a low VD corresponds to high Plasma Binding Concentration(FA 233, 2019). That's my main confusion with this question. +3
kevin  If it's high plasma binding, then it's low Vd. But, low VD doesn't necessarily require high plasma binding. Low Vd can simply be due to it being a large polar molecule +3
topgunber  So you the confusion is that VD of 1 means it stays in the circulation/ intravascular compartment. This would make you think that it would bind highly to protein in because of the low VD. But im assuming if it bound proteins it would not be cleared by the kidneys, so if this had a low VD (can be cleared at glomerulus) and if it bound plasma proteins weakly (allows the kidney to filter the substance) then it can be filtered into the tubular lumen. Now the pka. Bases when protonated (ph under their pka) become charged, while acids at ph under their pka get protonated are UNCHARGED, meaning in acidic urine acids become more lipophillic and can diffuse out of the tubular lumen. If we made the urine more basic, then we want to deprotonate the acid (ph higher than pka) so it will remain stuck in the tubular lumen as an ion. +



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submitted by โˆ—charcot_bouchard(574)
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pKa is pH at which any drug is at its 50% ionized state.

Now we are alk urine i.e inc pH. when pH>pKa it will have two diff path for acidic drug & basic drug.

Acidic drug will inc its elimination (inc ionized form), basic drug will be more absorbed. so we need to know the drug is basic /acidic.

Now if u alk urine its elimination inc. so it have to be acidic. or u can know its a sodi salt of drug with CNS property i.e most like Phenobarbital (Weak acid)

so if pKa of drug is 6---at pH 7 we will start eliminating

but if pKa is 0 we need to raise pH of urine at 11 to start eliminating.at that point prev drug (pKa=6) would be totally out of system.

thats why A is the right ans (pKa = 6)

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charcot_bouchard  Correction : Not 0. i means if pKa is 10 +3
charcot_bouchard  2nd update : cont to learn school grade chem. if pKa > 7 it is base. and if pKa is < 7 it is acid. Since we established the drug have to be a weak acid pKa cant be more than 7. +
dbg  thanks, but Pka and PH are not at all the same thing +2



 +3  upvote downvote
submitted by โˆ—monoloco(155)
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If you want to clear a drug, it is probably best that it not be bound to proteins (so that it gets filtered) and it has a low volume of distribution (so it isn't in the deep, hard to reach tissues).

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kingtime9119  But that doesn't make sense. Page 233 of First Aid 2019 edition clearly states that being plasma protein bound creates the lowest volume of distribution, because not being bound to proteins increases the chance it will reach deep into the tissues before it reaches the kidneys. Discrepancy with First Aid? +
haliburton  my reasoning was comparing two drugs, both with Vd of 1, the drug with the lower albumin binding would be cleared faster @kingtime. I don't think you're considering that A and B have equal Vd. +8
whyisthis42dollars  Being plasma bound may create the lowest Vd, but it doesn't mean it's going to be filtered by the kidney. Same reason why protein-bound calcium isn't filtered by the kidney. You're getting too hung up on Vd, but that's only one part of the equation here. +



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submitted by โˆ—lispectedwumbologist(122)
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Can somebody please explain why the pKa has to be 6 instead of 10?

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masonkingcobra  Since an ionized form is charged (by definition), it will not easily cross a nonpolar lipid membrane. Thus, it is important to recognize the potential of the drug to ionize in order to predict its solubility and the degree to which it can be reabsorbed. The degree of ionization is determined by the drugโ€™s pKa and the pH of its environment. Weak acids and bases are 50% ionized and 50% unionized when the surrounding pH equals the drugโ€™s pKa. At 2 pH units above or below the pKa of the drug, nearly 100% of the drug is ionized or unionized. +4
masonkingcobra  Basically weak acids are best excreted in alkaline urine, but weak bases are excreted more readily in acid urine. +
masonkingcobra  In summary, because this is a weak acid at pKa 6, making the urine alkaline will result it its ionization and excretion. Ionized cant move through lipid membranes so can't get reabsorbed and is pissed out. +20
yex  Following on masonkingcobra explanation: A pKa 4-9 can be either weak acid or base. Weak acid pKa 4-7; strong acid pKa 1-3 Weak base pKa 7-9; strong base pKa above 9 Differents pHs: stomach: 1-2 duodenum: 3-5 early jejunum: 5-7 late jejunum: 7-9 ileum: >9 urine: 4.5-8 Weak acids (pKa) gets absorbed in acidic (pH) environments and cleared in basic. Weak bases gets absorbed in basic environments and cleared in acidic. THIS DOES NOT APPLY TO STRONG BASES OR ACIDS!!!! The best explanation for this is a Biochem lecture from Pass Program and it is available on YouTube, its long but it is for sure worth it!! Look for 19 Biochemistry 1 from Pass Program on YouTube. +3



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submitted by โˆ—chandlerbas(118)
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alright lets do this. some of the comments were really well explained, however im going to try another route. lets deal with pKa since the other comments exaplained Vd well enough. kudos fellas/fellos.

first thing is you have to determine if its an acid or base. 90% of the time its going to be a weak acid, we simple dont formulate much medications as bases in general. also its sodium salt and CNS so you know it has to be phenobarbital. step (1) low pKa means acid (4-7). you must know this. (2) you must know that all acids start off neutral and then lose an ion --> becoming charged. and all bases start off charged and then lose an ion to become neutral (this is why we dont use basic drugs because this neutral charge has a high vd and deposits in tissues = bad in elderly). you want charged bc thats what is hydrophilic aka pee it out. (3) next use what i jjust said and apply it to this chart:

+2 = 99%

+1 = 90%

-1 = 10%

-2 = 1%

the first number represents the difference between pH and pKa (pKa is given by the question always), pH is what you changed when you alkalnized the urine. so for this question it would be: pH-pKa = high basic value (>7) minus pka ( weak acid 4-7).

now the second percentage represents the percentage of dissociated proton. so for an acid, they will become charged, this means that if the difference between the ph and pKa is over +1 then 90% of the acid will go from neutral to charged. if the ph is 2+ greater than pKA then 99% of the acid will have lost its proton and become charged

lets summarize this: were told its a weak acid = aka pKa between 4-7. we want to get to take the weak acid from its neutral form into a charged form to get rid of it. so we alkalanize the urine, because bases are higher pH you will get a more + number thus the weak acid will go from neutral to charged and be excreted.

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submitted by โˆ—strugglebus(189)
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I was wondering if it was to allow for partial CNS penetration since the drug is supposedly supposed to have CNS effect

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submitted by sha2507(0)
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for weak acids pH=pka + log (A-)/(HA) aka henderson hasselbach equation if you solve this, you'll get that pH - pka = log(A-)/(HA) and then again you will get 10 to power ph - pka = A-/HA. [Refer to link in comments] now considering that the ph of our body is 7.3 something, we can solve for pka 10 and pka 6 using this formula. That is for pka 6 and body ph 7.3, it will be 10 to the power of 1.3, would mean that A/HA ratio is a positive number, implying that A- > HA. whereas for when pka is 10, the A-/HA ration is 10 to power of -2.7, meaning that HA>A-.

And as already mentioned in the above comments, we need an iconic form, to eliminate the drug, it would be preferred if the pka is 6 as in that case, A-(ionic) would be in more concentration.

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sha2507  https://www.khanacademy.org/science/chemistry/acid-base-equilibrium/buffer-solutions/v/ph-and-pka-relationship-for-buffers refer to this video, to understand it a little better, and for the formula with the table, skip to 7:26 +



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submitted by kingtime9119(0)
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submitted by sway(0)
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so what if this was inversed where the drug in question was a base and that urine was acidified.i know the pKa would need to be >7 but what about the pH

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submitted by โˆ—haliburton(225)
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[comment moved to subcomment]

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