Twin Cities Toxicology
Another possible antidote for poison-induced cardiogenic shock…
In an attempt to keep you up to date on what’s going on in the world of antidotes for cardiogenic collapse caused by drugs, I’d like to call your attention to another couple articles and an antidote that’s probably new for you. This will be something to add to the list in your head to somehow organize with fluid, calcium, high dose insulin, intralipid, glucagon, pressors, levosimendan, l-carnitine, methylene blue, etc.
Dr. Allan Mottram is a medical toxicologist and emergency medicine physician at the University of Wisconsin.  He teamed up with a couple of medical toxicologists out of Chicago (where he trained), Drs. Sean Bryant and Steve Aks, for this work.  The first study (here’s the PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20724913) looked at high dose cyclodextrin (CD, sulfobutylether-beta-cyclodextrin to be exact) in the setting of verapamil toxicity in rats.  The rats treated with the high dose CD actually did worse.  They theorized that this could have been due to the hyperosmolar load from the CD, and that further study was needed at lower doses. 
The second study (http://escholarship.org/uc/item/07p476t8) was the follow up and looked at a lower concentration of the same CD.  This showed promise in that there was a statistically significantly increased time to asystole in the CD-treated verapamil-toxic rats. 
CDs are hydrophilic complexes that have a hydrophobic core.  Lipophilic molecules fit into that core.  They are often used to modify solubility and stability of drugs. Using CDs as antidotes has been done before (with rocuronium), but even in the nerdy world of toxicology this is not something commonly discussed, and certainly not often tried/studied. I look forward to more work on this subject, as CD use in the setting of overdose-induced cardiogenic shock is not ready for prime time yet, but shows some definite promise.
-Sam

Another possible antidote for poison-induced cardiogenic shock…

In an attempt to keep you up to date on what’s going on in the world of antidotes for cardiogenic collapse caused by drugs, I’d like to call your attention to another couple articles and an antidote that’s probably new for you. This will be something to add to the list in your head to somehow organize with fluid, calcium, high dose insulin, intralipid, glucagon, pressors, levosimendan, l-carnitine, methylene blue, etc.

Dr. Allan Mottram is a medical toxicologist and emergency medicine physician at the University of Wisconsin.  He teamed up with a couple of medical toxicologists out of Chicago (where he trained), Drs. Sean Bryant and Steve Aks, for this work.  The first study (here’s the PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20724913) looked at high dose cyclodextrin (CD, sulfobutylether-beta-cyclodextrin to be exact) in the setting of verapamil toxicity in rats.  The rats treated with the high dose CD actually did worse.  They theorized that this could have been due to the hyperosmolar load from the CD, and that further study was needed at lower doses. 

The second study (http://escholarship.org/uc/item/07p476t8) was the follow up and looked at a lower concentration of the same CD.  This showed promise in that there was a statistically significantly increased time to asystole in the CD-treated verapamil-toxic rats. 

CDs are hydrophilic complexes that have a hydrophobic core.  Lipophilic molecules fit into that core.  They are often used to modify solubility and stability of drugs. Using CDs as antidotes has been done before (with rocuronium), but even in the nerdy world of toxicology this is not something commonly discussed, and certainly not often tried/studied. I look forward to more work on this subject, as CD use in the setting of overdose-induced cardiogenic shock is not ready for prime time yet, but shows some definite promise.

-Sam

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