Diltiazem: for those tough cocaine fixes…

Ever wondered why each day as you took your next diltiazem (Cardizem) pill that “hey, I’m not craving cocaine today!”?  Well, wonder no more.  Scientists at Boston University have recently found that diltiazem, a calcium channel blocker used to control blood pressure, can actually reduce cocaine cravings, at least in mice (they get all the good drugs!).

Dopamine and glutamate are two chemicals in your brain that are blamed for the highly addictive properties of cocaine.  Both of these chemicals are basically pleasure compounds, and your brain has a lot to learn from pleasure compounds.  The happier your brain gets, the happier it likes to stay, so therefore you become addictive to certain drugs, like cocaine, that release these compounds.  Where diltiazem comes in is that, as a calcium channel blocker, it disrupts the communication between these compounds, in which calcium is needed.  No calcium means no communication, which leads to less happy feelings from the cocaine, and less cravings.  No wonder you haven’t had any of those cocaine cravings while on diltiazem all those years.

This research will be published in the March issue of Nature Neuroscience.  There are currently no drug therapies for cocaine addiction.  Do not, however, start taking diltiazem if you are addicted to cocaine, unless you are a rat, in which case if you are a cocaine addict rat, please e-mail me…

Your pee is changing lives, one fish at a time

Are you a woman?  Are you on birth control pills?  Are you urinating?  If you answered yes to all three questions, then you might be to blame for the recent surge in females in fisheries.  Small species of fish have been found to be changing sex in rivers and streams that you pee into.  Now, I know you urinate into a toilet (at least I hope so…) but where do you think that urine ends up?  It’s cleaned and dumped into a lake, and the estrogens in your birth control are pee’d out and affect the fish population.  Think Jurassic Park.  So, how can this happen?

Well, when you take a drug, some (if not most) of the time you simply eliminate it by peeing it out, unchanged.  Sometimes your liver does most of the work, changing the drug around so you can pee it out easier, but for estrogens, you simply pee it out.  This is why you have to take drugs every day, because your body is very good at getting rid of them.  This goes for chemotherapy and radiation chemotherapy as well, as your urine could actually be radioactive, but I digress…

So, the medicines you take are leaking into the streams, the fish swim around it and change sexes.  So?  Well, too many females are a problem (in more ways then one…).  You cannot reproduce without males and females, so you can’t make babies.  No small fish babies equals no big fish food.  No big fish food equals no big fish.  No big fish equals no food for us.    This effect has also been seen in antibiotics as well, causing fish to succumb to superbugs too. 

Well, at least there will be more breast meat…Oh wait, that’s chicken.  Oh, and the fish’s acne has cleared up, and the sex is much safer…

Vytorin, Zetia and the ENHANCE Trial Hype

Ok, so by now, you probably have heard that Vytorin is a horrible drug and everyone should stop taking it.  Relax, while some parts of this study have shown to be harmful, we need to look deeper to see if Zetia (one of two drugs in Vytorin) actually has a harmful effect.

So, what was the study?  Well, take 720 people with familial hypercholesterolemia (they all had high cholesterol from their families) and randomize them to either receive high dose Zocor (80 mg a day) or Vytorin (80 mg of Zocor and 10 mg of Zetia a day).  Then, measure the carotid artery (the one in your neck) for diameter and see how much plaque has grown in the artery.  Less plaque leads to less cardiovascular events, right?  Well…

Ok, so the Vytorin (Zetia and Zocor together) group had an increase in plaque diameter of 0.0111 mm and the Zocor alone group their plaque grew by 0.0058 mm.  This may seem like a huge difference, but statistically it was not.  There was no statistical significance between these two numbers.  (p=0.29)  (WTF is that p number?  Basically if the numbers were actually different, and didn’t happen by chance, then the p value should be < 0.05  0.29 is not less than 0.05, and therefore not statistically significant difference.  Don’t worry about it.)  So basically yes, Vytorin did cause the plaque to grow faster than with just Zocor alone, but this could have happened by chance.

Now, the end-point in this study was the plaque, however, they did follow up on deaths, non-fatal heart attacks and non-fatal strokes, and so on and so on.  These are the numbers you are worried about when it comes to cholesterol.  Yes the drugs do lower cholesterol, but if you do not lead to less deaths and heart attacks, what does it matter, right?  So, we should find, according to the hype, that the people on Vytorin had more deaths, heart attacks and strokes, because, by gosh, their carotid arteries grew plaque faster, right?  Wrong…  There were no statistical difference between the two groups in deaths (0.6 % Vytorin vs. 0.3% Zocor), non-fatal heart attacks (0.8% vs. 0.6%) and non-fatal strokes (0.3% vs. 0.3%).  p=NS for all (there’s that darn p guy again.  NS?  that means not signifcant, or basically not <0.05, the magic number).  So, was there a value that there was actually a difference between the two groups?  Yep.  LDL (the bad cholesterol) was lowered greater in the Vytorin (Zocor/Zetia) group (58%) vs. the Zocor alone group (41%).  p<0.01.  (Damn you p guy!  Ok, since p value here was <0.05, then there is a significant difference between the two groups.  The only value (LDL) that was found to be significantly different between the two groups in this study.)

So, what could be concluded from this study, according to the outcome?  Yes, Vytorin was found not to have slowed down the progression of plaque build-up in the carotid arteries vs. Zocor in the study, but not by a great enough margin that it couldn’t have just happened by chance.  There was no difference between deaths, heart attacks, or strokes in the study (what we actually care about as an outcome, who cares if the patient has a 0.0053 mm more growth of plaque if it doesn’t do anything), and the bad cholesterol was actually lower in the Vytorin patients.  My conclusion is that Vytorin is a good drug at lowering cholesterol, but it has not been shown to reduce the risk of death or heart attacks (unlike Zocor, which has been proven to do so).  It may just not keep you from dying…So, what should you do if you are currently taking Vytorin?  Just keep taking it as prescribed by your doctor, and if your doctor asks you to switch medications, ask him if he has actually read the study.  

However, there is one thing I didn’t like about this study, and was its timing in getting the results.  This was a two year study that ended in April 2006, and because the drug company thought the public were going to freak out when the results came out (which it did) that the company (Merck & Schering) did not release the results until Jan 2008, nearly two years later.  They say it was because it was hard to calculate the results.  B.S.  You just didn’t want the people to stop taking Zetia, because the press would interpret the results incorrectly (which it did) and physicians would stop prescribing the medicine (which they did).  I wonder if all those physicians actually read the study, or just the New York Times. 

P.S.  Look!  Just another study that proves lowering cholesterol does not affect death rates, number of heart attacks or the prevalence of stroke.  Looks like there may be some hype in all of these cholesterol-lowering medications, but I guess that’s a topic for another post.  Funny how no one drew that conclusion from this study.