heath ledger

I saw the news on MSN a few moments ago.  I gasped so loud.  It is sad.  He has a young daughter.  And, what a handsome man and good actor.  I feel badly for his family

I hope the autopsy results come back quickly-- they said 10 days for toxicology-- so the speculation can stop. I wish this would knock some sense into the partying young celebs that life is too damn short to risk their lives- no matter what the cause of his death.

I think feeling undestructible is part of being young--- but the DUI party hearty crowd seem be going out of their way to prove it. I was glad to see Nicole Ritchie accept her punishment and she seems to have turned her life around. I hope she got herself some help for her issues, because it's a big burden for a little baby to carry her mom's sobriety on her tiny shoulders. Her husband or boyfriend seems like he's a good influence too. If it's true Britney wants to have another baby I DO NOT RECOMMEND that-- frightening.

Oh Susie, I hadn't heard that!  You are absolutely right about the combination of prescription drugs.  It is a major problem, especially with people with multiple health problems.  Even with tamoxifen, SSRI's can cause the tamox to not convert properly.  I did think it odd since he wasn't known for being a big party person. 

For drugs that were named off were Lunesta, Ambien, Xanax and Ativan.  I've had insomnia and it sucks big time.  However, back then I had nothing to take.  And, to this day I am still a bit scared to take a med I've never taken.

I feel so badly for him and his family.  And that little sweet baby girl.  How sad.

Shirley

I think it is sad that Heath Ledger died. I feel sorry for his child.  I am not going to preempt the autopsy as the final results are not in.

However I will say I am absolutely tired of the amount of media coverage this is receiving in Australia - pages and pages of it.  There are many other tragedies that don't receive this kind of coverage.

The day before he died there was a truly terrible car accident in Melbourne where two true innocents, a new born baby and a five year old boy, lost their lives.

Their 29 year old mother was trying to enter a notorious ring road where the difficulties of merging were well known.  Her Honda Accord was hit from behind by a refrigerated truck, not a real large one.  The impact virtually destroyed the back half of the vehicle. In the back was the grandmother (who I suspect had just been collected from the airport) and the two children.  The three back seat passengers were trapped for some time.  The newborn died instantly.  The critically injured grandmother was very distressed when she was freed from the car as the children were still inside.  The little boy was freed but died from a cardiac arrest on the way to hospital despite the best efforts of the paramedics.

The Mum was not critically injured but stayed in hospital to be close to the grandmother.

Did the grandmother make it?  Was the truck driver charged? Who knows, the media have totally dropped this story to make room for Heath Ledger - pages and pages of it.

Sorry for sharing, but this accident has really hit me hard even though I don't know the people involved.  I can't stop thinking about that lady losing both her kids and her mother critically injured.  I think I just needed to have a rant about it.

Take care,

Sandy

Sandy you make an important point about Ledger-- and any celebrity death. We've had our share of "breaking news" about Heath's death, including that his casket was removed from the funeral home and was perhaps going back to australia. Huh??? How is this breaking news?

I am sick to death hearing about Britney too, shirley.

The media speculates about Heath's death because people are interested and tuning in-- it's all about ratings. When a young celebrity dies, people are going to be curious and speculate, that's just human nature just like when Anna Nicole died. Adding to the mystery is that the masseuse called Mary Kate Olsen before calling 911-- only a star would do that. His parents are probably savvy enough, and being in australia to not turn on the tv with all the speculation going on. Heath's death is incredibly sad, such a talent. Now if it had been Britney, I wouldn't be so sad.

Yes I agree that this shouldn't be a lead story around the world, but I think this death has some unique implications for us BC patients.

Many of the medicines that they found in his body are those that many of us are prescribed, especially those of us on the AI's who are in moderate pain and fighting insomnia. I think this is a cautionary tale for all of us.

That one of the powerful ones turns out to be the OTC Unisom sleep tabs

(Doxylamine).

Add to that the notoriously long half life of Benzodiazopines and a pain pill or two and you have a recipe for disaster.  You could take this stuff hours before and not realize its not out of your body.

The other thing that has implications for us is the same concerns we have regarding tamoxifen. (ie. being how we metabolize the drug )

I found this very interesting commentary on a medical blog today. 

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I believe that press reports immediately after Ledger's death noted that he had Rxs from multiple physicians, no surprise given that he was filming all over the world then living in NYC.

The metabolism questions from DM and N.B. deserve a whole post and are rather complicated. While there is no CYP overlap between benzodiazepines (3A4) and the benzomorphan opioids (2D6), people vary quite a bit in CYP2D6 activity and can fall into poor or rapid metabolizers. The counterintuitive factor to consider is that 2D6 converts oxycodone and hydrocodone into the more active oxymorphone and hydromorphone, respectively. So, if Ledger had a CYP2D6 rapid metabolizer phenotype, that would be a bad thing.

As N.B. points out neither benzodiazepines nor opiates are particularly noted for induction of Phase I or Phase II drug metabolizing enzymes.

The common thread between benzodiazepines and benzomorphans is that both classes undergo glucuronide conjugation via UGT2B7 activity. This is primarily an inactivation pathway (although some opioids are more active as glucuronide conjugates, flying in the face of the pharmacology I learned). So, you essentially got five drugs where some could act as competitive inhibitors of the inactivation of one or more of the others. That would be consistent with the mixture being worse than the sum of the parts pharmacokinetically. However, even just the additive CNS depressant effects of all the drugs would be enough for pharmacodynamic additivity or synergy without invoking metabolic arguments.

Finally, doxylamine is also the antihistamine in NyQuil, well-known to knock the hell out of people far more than Benadryl/diphenhydramine. Moreover, it is sold as a sleep aid in Australia in dosage forms (50 mg) larger than those in the US (6.25-25 mg).

If you're confused by now, you should be. My feeling is that this drug combination could be lethal even at recommended doses of each without invoking drug metabolism interactions. However, adding in the competition for glucuronidation makes this combination even worse.

Posted by: Abel Pharmboy | February 6, 2008 8:51 PM