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Fat Absorption and MTP Inhibitors – Lipid Control

by Pravin Shukle, MD
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    00:01 Let's talk quickly about fat absorption inhibitors. Orlistat which is sold as Xenical is sold as an obesity treatment but it does have reduction in cholesterol too. Now 50% of patients who take orlistat have a 5% reduction in body mass.

    00:18 The reduction in diabetes mellitus incidence is also recorded, probably related to weight loss. There is a modest reduction in blood pressure and a mild reduction in LDL as well. Now this reduction in LDL is actually independant of the weight loss.

    00:33 So, whatever LDL reduction you get from weight loss, there seems to be a little bit more. In terms of the side effects of orlistat, the FDA recently released a warning about hepatotoxicity or possible hepatotoxicity but this flies in the face of some evidence from the United Kingdom which used a 94000 patient study to show no causal increase in hepatic injury with this medication. We are still going to be very careful in clinical practice, but just to let you know that there is a bit of a debate on this. There is an increase in renal failure that's been documented and there is a theoretical concern about colon carcinoma because we think that there may be a possible link between the content of fecal fat and colon cancer although that has'nt been proven at this point in time. Let's move on to the MTP inhibitors.

    01:30 This is a new class of drugs. They're fiendishly expensive but they are now coming on to the market. The prototypical drug I would say is lomitapide or Juxtapid. It's an oral tablet. Now it acts on the microsomal triglyceride transfer protein or MTP, and it is inhibitor of that protein. VLDL and triglyceride assembly and secretion in the liver is what is being affected here.

    02:02 It is used for the treatment of familial hypercholesterolemia. And what it does is it reduces VLDL and all of the non-HDL fraction of the cholesterol profile. It also will reduce apolipoprotein B, because remember that apolipoprotein B are these proteins that are going to be attached to either VLDL or LDL. It can be used in combination with statins and some reports indicate up to 60% reduction in LDL cholesterol with these medications. The adverse events, it may increase hepatic triglyceride levels and it may cause a transaminitis.

    02:45 Mipomersen is also an MTP inhibitor and it is a once a week injection. It targets the messenger RNA for ApoB.

    02:57 For the treatment of homozygous familial hypercholesterolemia. We call that HOFH to distinguish it from HEFH which is heterozygous familial hypercholesterolemia. With this treatment you get a 25% reduction of LDL. And remember that these are a group of patients who don't respond well to statins. So, a 25% reduction in these people is actually pretty good.

    03:21 It decreases hepatic and plasma ApoB and C-III. It can be used in combination with statins as well. The adverse events, once again it may increase hepatic triglyceride levels, and of course a transaminitis.


    About the Lecture

    The lecture Fat Absorption and MTP Inhibitors – Lipid Control by Pravin Shukle, MD is from the course Cardiovascular Pharmacology. It contains the following chapters:

    • Fat Absorption Inhibitors
    • MTP Inhibitors

    Included Quiz Questions

    1. Mild reduction of triglyceride levels.
    2. 5% reduction in body mass
    3. Mild reduction of LDL
    4. Modest reduction in blood pressure
    5. Reduction of diabetes mellitus incidence
    1. Lomitapide
    2. Mipomersen
    3. Bile Acid Resins
    4. Ezitimibe
    5. Orlistat
    1. Increased hepatic triglyceride levels.
    2. Theoretical increased risk for colon cancer
    3. Decreased transaminase levels
    4. Increased risk for diabetes mellitus
    5. Increased risk for renal failure

    Author of lecture Fat Absorption and MTP Inhibitors – Lipid Control

     Pravin Shukle, MD

    Pravin Shukle, MD


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