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NBME 20 Answers

nbme20/Block 3/Question#23

A 50-year-old woman is brought to the emergency ...

pKa: 6.0; Protein binding in plasma: 20%; Volume of distribution at steady state: 1 L/kg

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submitted by hayayah(349),

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.

 +2  upvote downvote
submitted by monoloco(49),

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).

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. +1  

 +2  upvote downvote
submitted by lispectedwumbologist(23),

Can somebody please explain why the pKa has to be 6 instead of 10?

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 drug’s pKa and the pH of its environment. Weak acids and bases are 50% ionized and 50% unionized when the surrounding pH equals the drug’s pKa. At 2 pH units above or below the pKa of the drug, nearly 100% of the drug is ionized or unionized. +1  
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. +1  
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. +1  

 +1  upvote downvote
submitted by charcot_bouchard(43),

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 that point prev drug (pKa=6) would be totally out of system.

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

charcot_bouchard  Correction : Not 0. i means if pKa is 10 +  
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 +  

 +0  upvote downvote
submitted by kingtime9119(0),

[comment moved to subcomment]

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submitted by strugglebus(63),

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 haliburton(74),

[comment moved to subcomment]