pharmacokinetics/volume of distribution

[aspiringmd1015]

not understanding this stuff properly, where can i properly attack this weak point of mine to where i can answer questions confidently. no overkill, just something to complete my concepts.

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[TheBDP]

not understanding this stuff properly, where can i properly attack this weak point of mine to where i can answer questions confidently. no overkill, just something to complete my concepts.

I thought FA covered it pretty well, but maybe that's just me?

 

[Transposony]

Kaplan Pharmacology by Harris

 

[aspiringmd1015]

Kaplan Pharmacology by Harris

dr. harris says one thing thats confusing me, for steady state, he says its strictly dependent on t1/2 and irrespective of dose size, and frequency of administration. But then he says if you give a loading dose you can reach steady state quicker. help.

 

[Transposony]

dr. harris says one thing thats confusing me, for steady state, he says its strictly dependent on t1/2 and irrespective of dose size, and frequency of administration. But then he says if you give a loading dose you can reach steady state quicker. help.

Those are two entirely different concepts:

1st one is about maintenance dose where the steady state is reached for that particular dose depending on the half life.
2nd one is about loading dose where the whole idea is about reaching steady state quicker.

If you look at the equations for maintenance dose and loading dose you will note that:

1. Maintenance dose depends on the clearance and
2. Loading dose depends on the VoD.

This makes sense since maintenance dose (amount you put in) will depend on amount which is eliminated as compared to loading dose where distribution of drug in body will determine it's concentration.

 

[DrPicard]

dr. harris says one thing thats confusing me, for steady state, he says its strictly dependent on t1/2 and irrespective of dose size, and frequency of administration. But then he says if you give a loading dose you can reach steady state quicker. help.

Irrespective of dose size if all doses are the same in magnitude. A loading dose is larger than all subsequent doses, that's how it helps reaching steady state sooner.

Otherwise, no. of doses relates to steady state time, and size of dose to concentration at steady state.

 

[aspiringmd1015]

I understand how MD is dependent on clearance and LD on VOD and not clearance(as its only given once so you dont have to worry about what the kidneys are doing), i also appreciate you guys helping, but how can you reach steady state "quicker" if steady state is only dependent on half life?

 

[worldbeater]

There is a VOD question on World/NBME that we discussed at length earlier, it will be helpful for you:

http://forums.studentdoctor.net/threads/nbme-12-discussion.818602/page-13#post-17509313

I got this question wrong, but figured it out. This is a concept of fat soluble vs. water soluble drugs. Let's define the two different axis first. Your x axis is time, your y axis is plasma. Plasma is mostly composed of water, so your in a water soluble environment.

Great. Now we have two graphs, a normal patient who's curve goes upwards and at hits the y axis in a faster time period. Then we have an obese patient who's graph is linear. It takes longer to hit the same spot on the y axis. This makes sense, because the obese patient carries more fat. Fat does not mix with water, so it's going to take longer to reach same point in the plasma.

So the answer is volume of distribution, let's talk about normal first. The normal VOD is 41 L and is composed of plasma volume (3-5L) + interstitial volume (14-16L) + cellular volume (remainder). Volume of distribution is how much of the drug is present in all three of these components. So if a patient is obese, most of the drug will be in the cellular volume (fat area), then in the interstitial volume, and a portion will be in the plasma volume. He will have a higher VOD than a normal patient, but less in the plasma component.

The matching Uworld question is Q1710, and they just flipped it, asking about a patient having a drug with a VOD of 4.5L (which is low) and asking what properties does it have? The first 3-5L is in the plasma. Plasma is water soluble or highly charged (which is the answer). The explanation has the all the VOD info I provided above.

 

[aspiringmd1015]

Those are two entirely different concepts:

1st one is about maintenance dose where the steady state is reached for that particular dose depending on the half life.
2nd one is about loading dose where the whole idea is about reaching steady state quicker.

If you look at the equations for maintenance dose and loading dose you will note that:

1. Maintenance dose depends on the clearance and
2. Loading dose depends on the VoD.

This makes sense since maintenance dose (amount you put in) will depend on amount which is eliminated as compared to loading dose where distribution of drug in body will determine it's concentration.

transposony the great, if you could chime in on this please, kaplan states steady state is irrespective of dosing size and frequency, i understand size, but why frequency? ie if i gave a patient a dose at every t1/2, for example 100 after every 4 hours, but on the 3rd dose, i gave 100 mg, but i gave it after 2 hours instead of 4 hours, wont i reach steady state quicker?