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  #1  
Old 02-24-2011
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Arrow Drug bio availability

A group of investigators is currently conducting an experiment on a newly developed synthetic opioid analgesic. This drug has twice the analgesic capability of morphine. After oral ingestion by several volunteers, the plasma concentration of the drug is measured and is determined to be subtherapeutic. After rectal administration of the same dose of the drug the measured plasma drug concentration reached therapeutic levels and is almost double the level measured after oral intake. Which of the following factors is the main determinant of drug bio availability after oral intake accounting for the difference in drug concentrations described above?


A. Intestinal blood flow
B. Kidney blood flow
C. Liver blood flow
D. Absorptive surface
E. Absorption rate
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Old 02-24-2011
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Such an easy Q. It is liver where most detoxification occurs.

But i smell a conspiracy in the Q. it is intestinal blood flow (portal flow) that takes drug to the liver. Liver blood flow will take it to the body. So i go with A.
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Quote:
Originally Posted by drahmednawaz View Post
Such an easy Q. It is liver where most detoxification occurs.

But i smell a conspiracy in the Q. it is intestinal blood flow (portal flow) that takes drug to the liver. Liver blood flow will take it to the body. So i go with A.
won't the drug absorbed from rectum have to go through liver??the drug level is increasing on rectal administration???
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Quote:
Originally Posted by drahmednawaz View Post
Such an easy Q. It is liver where most detoxification occurs.

But i smell a conspiracy in the Q. it is intestinal blood flow (portal flow) that takes drug to the liver. Liver blood flow will take it to the body. So i go with A.
80% of blood to liver is brought by portal vein(20% by hepatic arety) so i think liver blood flow means portal flow not intestinal flow....

though i think your answer may be right because of different reason:
the high concentration in rectal administration may be due rich blood supply of rectum

So i wil go with A
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Old 02-24-2011
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Quote:
Originally Posted by rsin21 View Post
won't the drug absorbed from rectum have to go through liver??the drug level is increasing on rectal administration???
Rectal blood flow by-passes portal system. It dumps directly into body system.
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Quote:
Originally Posted by drahmednawaz View Post
Rectal blood flow by-passes portal system. It dumps directly into body system.
could plz tel where the veins of rectum(superior,middle,inferior) drain???

m not sure but i gues it drains in inferior mesentric vein which with splenic vein forms the portal vein..
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Old 02-24-2011
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Arrow

Hint: consider the first pass metabolism...
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Default C

I would say C, liver blood flow. I believe the question is testing our knowledge of the First-pass effect since oral administration would diminish bio availability of the drug. Liver blood flow to me sounds like the Portal system, which is responsible for the first pass effect.

Intestinal blood flow just doesn't sound as correct as Liver blood flow since intestinal blood flow can go to the systemic circulation as well. This is why rectal administration leads to higher levels, but this is not what the question is asking imo.
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Quote:
Originally Posted by apx85 View Post
I would say C, liver blood flow. I believe the question is testing our knowledge of the First-pass effect since oral administration would diminish bio availability of the drug. Liver blood flow to me sounds like the Portal system, which is responsible for the first pass effect.

Intestinal blood flow just doesn't sound as correct as Liver blood flow since intestinal blood flow can go to the systemic circulation as well. This is why rectal administration leads to higher levels, but this is not what the question is asking imo.

Ohhh! i am confusing portal and intestinal blood flow. Liver blood flow, portal flow and intestinal drainage are the same things. Intestinal blood flow refers to arteries that supply intestine.

Obviously Choice is C.
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Quote:
Originally Posted by rsin21 View Post
could plz tel where the veins of rectum(superior,middle,inferior) drain???

m not sure but i gues it drains in inferior mesentric vein which with splenic vein forms the portal vein..
My anatomy is very weak, but i am pretty sure that rectal blood by-passes portal system. May be through iliac veins into inferior vena cava. It is not inferior mesenteric vein.
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Old 02-24-2011
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Arrow

Damn!!!! that hint was so obvious.

Finally you all got it right, The correct ans is C) Liver blood flow

Oral bioavailability is dependent on the absorptive properties of the drug as well as its first-pass metabolism. The first-pass, or pre-systemic, metabolism of a drug occurs en route to the systemic circulation by enzymes present in the gutwall and lumen as well as the liver. Bioavailability refers to the fraction of administered drug that reaches the systemic circulation in a chemically unchanged form. When a drug is absorbed by the Cl tract after oral administration, it first enters the portal circulation before gaining access to the systemic circulation. If the drug is metabolized extensively by the liver (high first-pass metabolism), the amount that reaches the systemic circulation, and therefore the bioavailability, will be low.

In order to efficiently use drugs with a high first-pass metabolism, other routes of administration are typically employed. For instance, nitroglycerin can be used for preventing or treating anginal pain, but because it has a very high first-pass metabolism, not enough drug reaches systemic circulation to be effective. To circumvent this shortcoming, nitroglycerin tablets are given sublingually where they bypass the first-pass metabolism by entering the systemic circulation directly via the sublingual capillaries and arterioles. Propranolol and lidocaine also have a very high first-pass metabolism and thus have better bioavailability through IV or subcutaneous methods.

Rectal drug administration, such as with suppositories, partially by passes first-pass metabolism. Recall that the rectum is drained by the superior, middle and inferior rectal veins. The superior rectal veins drain to the portal circulation via the inferior mesenteric vein. The middle and inferior rectal veins, however, drain to the systemic circulation via the internal iliac and internal pudendal veins, respectively. Thus, two-thirds of the venous drainage of the rectal region goes directly into the systemic circulation, thereby increasing the bioavailability of drugs that are otherwise highly cleared by the liver after oral administration. The amount of drug exposed to the liver within the portal blood flow is the major determinant of hepatic or first-pass metabolism.
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i just luv ur xplanation aktorque

thnx for clearin the doubts
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