September 19, 2012

  • Need help with a math/science/medical question. . .

    I'm running out of resources to figure this out - math makes my head explode, lol.  Anyway, I participate in Websleuths and we're discussing a case of an amitriptyline overdose. The medical record states that 5 hours after being pronounced dead amitriptyline levels were 7909 ng/mL with nortriptyline levels of 2833 ng/mL.  According to my research amitriptyline breaks down into noritriptyline so this report is stating she still had 7909 ng/mL of amitriptyline in her blood, and the 2833 ng/mL of noritriptyline is broken down amitriptyline.  Basically, I'm trying desperately to figure out how many mg of amitriptyline would have to be ingested to get those levels.  I know this is a long shot, but I also know some of you out there are pretty damn smart and, again, I suck at math, lol.  

Comments (18)

  • That would depend on the method of ingestion as well as the rate of catalysis from ami to nori

  • @QuantumStorm - Thank you!  We don't know for certain the method of ingestion, although there were fragments of Flexeril pills found in the gastric contents.  There were no amitriptyline pill fragments found.  They were trying to figure out how many pills would need to be taken to reach those levels in an attempt to rule out pills (by sheer number needed), thereby suggesting it had to be a liquid and possibly injected, thereby making it more likely to be a murder than a suicide.  We don't even have the height/weight of the victim.  I'm thinking that with the very limited information we have (all listed above) there is no way any of them could accurately determine the amount of amitriptyline taken, let alone the method.  Would that be correct?  

  • @Melissa___Dawn - Hmmm, it occurred to me that if this is something readily available via prescription or over-the-counter, it might be possible to trace the medical testing data for this drug (via the FDA or something) and find out what the rate of absorption into the bloodstream is. I'm guessing they might have data on both human absorption as well as testing on mice and other animals.

    Thus if you know the absorption rate, AND if you know the time of death and the time the blood test was taken, you can work backwards from the blood test time to the time of death by using the absorption rate. Then, you can figure out roughly how much Ami was in the blood at the time of death. Since it's in ng/mL, you'd have to convert to mg, which would go something like this:

    ng/mL * (number of mL of blood in the human body) *(1mcg/1000ng)*(1mg/1000mcg)

    You'll have to google the total volume of blood in the average human body. Better yet, if you know what the dimensions of the dead person are, you might be able to estimate it with better accuracy.

    The result of that calculation should give you the rough amount of mg of Ami needed to have those concentrations; then you can divide that by the amount per typical Ami pill to get the total pill count. Again, it's going to be a rough estimate b/c absorption is rather complex and involves a lot of factors that aren't being considered here, but it'll give you a ballpark estimate at least.

  • @QuantumStorm - We don't have much information at all - it's in a letter of a second opinion on the autopsy and the doctor who wrote the letter did not examine the body, just the reports.  This is literally all the information we have:  http://morganingram.com/wordpress/?paged=2  I tried to C&P the letter but it wouldn't work - you have to scroll down towards the bottom of the page to get to the letter.  There's one paragraph where we get the toxicology results, and one paragraph further down where they do mention that the blood samples were peripheral blood and done "relatively quickly" following death.  

    I tried to figure it out myself and this is what I came up with (C&P from my reply on the other board):  

    Again, I absolutely suck at math and it makes my head hurt, so I have no doubt I'm wrong - I'm just trying to understand. I'm confused with the first conversion, as using this converter:http://www.convert-measurement-units...p?type=densityI entered 7909 ng/ml and selected to convert to mg/l and it showed 7.909 mg/l, not 7909 mg/l. A matter of a decimal point, but the original conversion makes no sense because it's not actually converting anything if the answer is the same, right?

    The next one I'm confused about is if we just converted it to milligrams per liter - that would mean 7.909 milligrams x 5 liters would actually equal 39.54 milligrams rather than grams, wouldn't it? This is probably where my mistake is, I probably just need the extra step how we got from milligrams to grams explained to me. Now, 39.54 milligrams in her system wouldn't be a lethal dose, however, if only 30% enters the blood stream (arrrrgh, percentages!), then wouldn't that mean, ugh, I'm going to use 25% because 1/4 is easier for me - if 25% were in her blood that would mean the total actual dose would be around 158 mg, which divided by 25 mg pills would actually be slightly over 6 pills. That's figuring 5% under the actual 30% because my math skills suck, and I didn't add in the amitriptyline that was already broken down to nortriptyline, but would imagine that would bump the total number of pills up by anywhere from 1 to 3 maybe? Still only equaling a total of possibly up to 10 actual pills of 25 mg of amitriptyline. 

    I appreciate your help, and I understand if you don't want to bother with this any longer, lol.  Originally we were just trying to come up with a ballpark figure of how many 25 mg pills she would have to take to get the toxicology levels reported.  She had a prescription for 25 mg tablets.   

  • Well if you're converting from ng/mL to mg/L, the conversion goes like this:

    1mg = 1000 mcg and 1 mcg = 1000 ng

    1mg = 1,000,000 ng

    1L = 1,000 mL

    (1ng/mL)*(1mg/1,000,000ng)*(1000mL/1L) = 0.001mg/L

    So 1000 ng/mL = 1 mg/L

    Thus the conversion from 7909 ng/mL to 7.909 mg/L seems legit.

    So,

    (7.909mg/L)*5L = 39.545 mg

    and remember, 1 gram = 1000mg

    so

    39.545mg *(1g/1000mg) = 0.039545 g

    This is the result if you want it in grams.
    Because I don't like working with decimals below 1 too much, we'll just stick with 39.545 mg for the next step.

    So if we assume that 39.545 mg is 30% of the TOTAL amount that was ingested, then

    39.545 mg / 0.30 = 131.82 mg

    So 131.82 mg / (25mg/tablet) = 5.27 tablets, rounded up would be 6 tablets at minimum.

    As for the 2833 ng/mL of nortriptyline, you'd have to look up the actual conversion process. Does the breakdown of 1 gram of amitriptyline break down into exactly 1 gram of nori, or is there some sort of loss? It probably won't be a perfect conversion rate but it would be good to know.

    Let's assume, though, that it's a 100% conversion rate. That is, for every 1 molecule of Ami, it converts into exactly 1 molecule of Nori.

    Then:

    2833 ng/mL * (5000mL in the human body) * (1 mg / 1,000,000 ng) = 14.165 mg

    Assuming the same 30% absorption rate you mentioned earlier,

    14.165 mg / 0.30 = 47.22 mg

    Which translates to roughly 2 more tablets.

    This brings your total to about 8 tablets of Amitryptiline. This assumes a 100% conversion rate from Ami to Nori, and a 30% absorption rate.

    I read the letter you linked, and while I am not a medical professional, I have something to say about that.

    I think that assigning the cause of death as undetermined is a wise move because of the way the coroner has handled the situation. However, I should add that muscle relaxants can be used as a part of a suicide regimen. In sufficient quantities they can cause cardiac arrest. After doing a lookup of cyclobenzaprine, I found that its effects are magnified when depressants/antidepressants are ALSO present in the bloodstream, and amitryptiline happens to be an antidepressant. I also take issue with the implication the second-opinion Doc makes by suggesting that a lack of suicide threats/declarations in the past means it is illogical to rule the death as a suicide. The absence of such past events, in my opinion, doesn't mean a death cannot be ruled as a suicide. In a lot of cases, many loved ones often don't see the suicide coming.

    I'm not arguing that the possibility of murder is out of the question, and in fact I DO think they should reclassify the death as undetermined. What I am saying, though, is that maybe the suicide option should be examined further. I find it rather odd that, for example, a stalker/rapist would not only use a skeletal relaxant but also happen to use EXACTLY the prescribed medication she had to kill her. It seems much more reasonable to assume that she stockpiled a small portion of her medication, and then obtained the muscle relaxant from a friend who had extra pills from an old prescription and forgot to dispose of them. I don't know if she knew of the interaction between the two drugs; she might have just figured that mixing a strong cocktail would do the trick.

    But then, I haven't read the entire story so I'm just saying this based on the second opinion letter. And I'm no expert in this stuff either, haha.

  • @QuantumStorm - Sorry, I fell asleep and then had a dentist appointment earlier today.  Okay, so the two of us are in agreement about it not really being a lot of pills.  Since we are missing a lot of information in figuring out the conversion we could be off, but I don't think we could be 387 pills off - which is one of the estimates given on the site, that she would have had to take around 395 pills to reach those levels.  I never got an answer to my math question over there, one response but not really an answer, lol.  

    I'm not sure if the cause of death should be reassigned to undetermined.  The mother is keeping a blog where she claims to be telling the true story of what happened, and she claims to have absolute evidence, but she hasn't produced anything substantial that couldn't be explained away as circumstantial/coincidental.  LE has stated that they were at the house at least 50 times in 4 months and that the case was bumped from misdemeanor harassment to felony stalking - the mother thinks that's evidence of stalking, but LE states they found no evidence of stalking.  Furthermore, all that is required to bump a case up to felony stalking is number of incidents reported - it doesn't mean they have to actually have physical evidence.  The only real possible evidence offered up has been one shoeprint discovered within the first week or 2 of rocks being thrown at the windows (which now they state it wasn't rocks thrown at the window, but someone tapping with a telescoping thingy) and at one point one of their wildlife cameras snapped a picture of an unidentified person crossing their driveway just after the deputies left the house after taking another report.  In 4 months they never found anymore shoeprints, and they claim one of the cameras captured a person running off their property the night she died, but they won't show it to anyone.  

    I do agree 100% with your statement that the absence of past events of suicide threats doesn't mean suicide is illogical.  The family claims that other than an incident of long-term CO poisoning due to a faulty furnace flu she was healthy.  However, apparently no one else in the family suffered CO poisoning while living in the same house, and none of their pets showed signs of illness or died.  The mother claims the first cause of death was wrong, but that it was the father that put that idea into the medical examiner's head by mentioning the possibility of Acute Intermittent Porphyria.  In Dr. Dobersen's letter he mentioned that AIP had been brought up as a possibility in her past medical records, but was never tested for, which is actually  not uncommon if the symptoms are successfully treated.  She started taking amitriptyline at the age of 12 for "abdominal pain", and took it for 6 years, only stopping on her own when she turned legal at 18.  That alone makes me think there was something more going on there that the parents aren't revealing regarding her medical history.  Also, untreated attacks of AIP can last weeks to months, and cause hallucinations.  

    All that said, and all the information I've looked over that I could find on this case, I'm back to leaning heavily to the initial cause of death actually being correct, that it was pulmonary edema due to acute intermittent porphyria.  The mother isn't finished revealing the whole story on her blog, so I will wait before making my final opinion on the issue, but if no actual evidence is given then I have to side with the initial cause of death, or possibly a suicide, but certainly not a murder.  While I have great compassion for this couple over the fact that they lost their daughter and at such a young age, what bothers me is that they haven't given any real evidence yet they are actually naming suspects and possibly ruining innocent lives.  

    Thanks again for your input with this!   Holy crap, this comment could have been a whole blog post, lol.

  • @Melissa___Dawn - 395 pills? Holy shit, she probably would have died from exposure to the OTHER ingredients in the pill way before the AMI had anything to do with it, haha. I doubt it's that high. And how would she get ahold of 395 pills in the first place? 10 or 20 I can understand because that can be stockpiled, but almost 400? Nah.

    After reading what you said about keeping the cause of death undetermined, I agree. I guess I was a bit hung up over the claim the coroner botched the original medical opinion but what you're saying makes more sense.

    The long-term CO exposure seems fishy. I wonder if there are any other medical conditions which have manifestations similar to CO poisoning, that might have something to do with her other medical issues.

    Glad to be of help! ^_^

  • @QuantumStorm - Yep, the pill count discrepancy is, from what I can tell, a mistake on their part because they are saying grams when they mean milligrams.  Unless we figured the math wrong, but I don't think we did.  That's why some of them on the board are hung up on it having to be murder and a liquid dose of amitriptyline.  But there were no signs whatsoever of forced entry or a struggle, so it just doesn't seem plausible.  

    As for the coroner botching the first medical opinion, well that's where I think it would come in handy if we could see the original autopsy and toxicology reports.  I do know that the family relentlessly pursued the first coroner to change the cause of death to undetermined and he apparently said the only other option he had was suicide, and after months he did change it to suicide.  I think suicide is still plausible, but only because Flexeril was found in her system as well, or even an accidental death due to the interaction of the amitriptyline and Flexeril.  Suicide wasn't the answer the parents wanted though, so they searched out another coroner who went over the reports and wrote that second opinion letter.

    Actually, what I find interesting is that she had, for several years, medical complaints of "abdominal pain and headache with cognitive disorders."  All of those symptoms fall under both Acute Intermittent Porphyria and CO poisoning.  However, I know someone who had a similar long-term CO poisoning and was not even treated for it, just fixed the problem and went on with life.  She took amitriptyline for 6 years for it - which just doesn't make sense.  

    I think the family is in denial and grasping at straws to find someone to blame, which I can understand but that doesn't give them the right to publicly name suspects and accuse people of murder.  They did a radio (phone?) interview over on Websleuths on Sunday night and after that the mother was speeding up getting to the end of the story.  The story takes place from August to her death in December, now today instead of giving us the final bits and actual evidence like everyone was expecting, she's gone back to late September.  I honestly don't think we are ever going to see any official documents regarding this case, but I'll keep following along just to see what, if anything, is finally revealed.

  • @QuantumStorm - Just thought you might be interested - tonight we got the official autopsy and toxicology reports - the M.E. estimated 18 (25 mg) pills.  We were close, a lot closer than those who kept saying it was 325 or at least over 100, lol.  Many of us have reviewed the reports and come to the conclusion everything was handled properly and it was indeed a tragic suicide.  

  • @Melissa___Dawn - BAM!

    We are so sexy smart.

  • @QuantumStorm - No doubt, I'm starting to think I'm getting the hang of this thing called math, lol!

  • @Melissa___Dawn - Practice makes perfect! Or in this case, suicide. 

  • How are you these days?   

  • @Edgebreak - Hi!  I'm doing good - trying to get shoveled out, lol.  Just been busy with work and stuff.  How are you?  

  • I'll trade you this California lack of Winter for a good solid snow.  :)  Eh, I have been continuing down the spiral of insanity that is my decent into madness.  I really should get on here and blog more, you know, as a cautionary tale for the audience at home.  

  • @Edgebreak - That sounds like a pretty good deal to me - I'm sick of all the white, lol.  Yeah, I should get back here and start blogging again, just been busy with work and home projects.  Hopefully things will settle down soon.  :) 

  • I certainly hope so.  A little calm between the storms of life is preferable in so many ways.  

  • I think I'd rather watch an hour of CSI on TV and let them figure all that stuff out for me!  haha.  I'm so bad!

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