toxicology


Whitney Houston (NY, 2009)

Whitney Houston (NY, 2009)

by Roseann Vorce, Ph.D., 
Department of Pharmacology and Toxicology
Michigan State University 

The headline was shocking – “Whitney Houston Found Dead”!  At age 48, the iconic singer was gone, found lifeless in a Beverly Hills hotel bathtub in a death scene we have seen too many times for the rich and famous.

Almost immediately, rumors began circulating that Houston’s death involved prescription drugs.  Some claimed that she died from a drug overdose; others claimed that she drowned while in a drug-induced stupor.  Toxicology test results will not be available for several weeks, and we might never know the full story.

Houston had a long history of substance abuse, and she had been in and out of drug rehabilitation programs for years.  With a history of using illegal drugs, many of which can cause death due to overdose, could Whitney Houston really have died due to the use of legally-obtained prescription drugs?

A vial of Xanax (alprazolam) was found in Houston’s hotel room, fueling speculation that prescription drugs caused her death.  Xanax is an anxiolytic drug that is commonly used to relieve stage fright, as well as anxiety caused by many other triggers.  A member of the benzodiazepine family of drugs, Xanax is one of the most frequently prescribed drugs in the United States.  The benzodiazepines work by increasing the effect of the endogenous neurotransmitter GABA (gamma-aminobutyric acid).  GABA is an important neurotransmitter that functions to inhibit activity in the central nervous system (CNS) by acting at the GABAA receptor.  The overall effect of GABA binding to the GABAA receptor is a dampening of activity in the CNS.  Benzodiazepines also bind to the GABAA receptor, where they enhance the effects of GABA on its receptor.  Because the activity of benzodiazepines relies on the presence of endogenous GABA, adverse effects of benzodiazepines are limited to impaired motor function (stumbling, difficulty walking), and drowsiness.  Only at very high doses can benzodiazepines cause death by inhibiting breathing.

Houston was seen drinking alcohol in the days prior to her death, and she reportedly indulged in champagne on the day she died.  Like the benzodiazepines, alcohol (ethanol) depresses the CNS.  Unlike the benzodiazepines, alcohol exerts a profound inhibitory effect on respiration.  The effects of ethanol poisoning include loss of consciousness (“passing out”), coma, and respiratory depression.  Ethanol poisoning is a medical emergency, and mechanical ventilation often is needed to maintain respiration.  Without treatment, a person suffering from ethanol poisoning can die.

Although Houston was reported to be drinking on the day of her death, there is no evidence that she was acutely intoxicated, nor is there evidence that she took an overdose of Xanax.  However, the combination of a benzodiazepine and alcohol can be deadly, even when the individual doses of each are not lethal.  Both alcohol and Xanax are CNS depressants, and their effects are additive.  Simultaneous administration of both can cause respiratory depression severe enough to stop breathing, a situation that ends in death if artificial ventilation is not initiated.  In contrast, some people die due to injuries suffered in accidents occurring secondary to intoxication with benzodiazepines and alcohol.  Automobile accidents, falls, and drowning in the bathtub all have been reported as the cause of death in people who are under the influence of benzodiazepines and alcohol.

We will not know the cause of Whitney Houston’s death until the results of toxicology testing are available. However, this story provides an opportunity to reinforce a warning that mixing prescription drugs with other drugs, including alcohol, can be very dangerous, and even deadly.

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“I don’t need help because if I can’t help myself I can’t be helped.” --Amy Winehouse

“Amy Winehouse found dead at her London flat…autopsy inconclusive…toxicology results expected in two to four weeks.” 

by Jane Maddox, Ph.D., Assistant Professor
Department of Pharmacology and Toxicology

Why do forensic toxicology results take so long? There are several reasons:

Multiple samples must be tested: blood, stomach contents, and urine are commonly first taken, but other tissues such as liver, brain, kidney, and vitreous humor of the eye may also be sampled.

If there are no obvious signs or symptoms linked to specific drugs or toxins observed at the time of death, testing for many different toxic substances must occur.

The tests must identify and quantify a wide repertoire of both legally prescribed drugs and illicit substances to determine if either any single drug or combination of drugs could have been the cause of death.

The initial tests would likely be immunoassays to screen for a wide variety of drugs suspected as the cause of death. These tests use antibodies to detect known drugs, but they can only measure a predetermined set of substances; therefore, if a new or unknown drug has been taken, it can be missed. Other analyses, such as mass spectrometry (that can identify unknown toxic substances) must also be performed.  Mass spectrometry is very sensitive and specific, but it also takes more time to complete.

Once potentially toxic substances have been detected, the concentrations in the sample must be compared with clinical data to determine if the dose, or combination of doses, was high enough to be lethal. In addition, samples may be retested in the same laboratory or sent to a second laboratory for confirmation. Again, these tests take more time. Confirmatory tests are important for several reasons: 1) to ensure scientific integrity of the data, 2) to defend against potential legal issues involved in cause of death, particularly in the case of a celebrity death.

As for the death of Amy Winehouse, it is complicated.

She was alone at the time of death, so no symptoms were observed, and it was reported that no drugs or paraphernalia were found on the premises. Therefore, important clues to direct the toxicology testing were lacking and the search could take some time to complete.

NuclearExplosionJapan

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

The recent earthquake and tsunami in Japan has caused severe destruction and has damaged a nuclear power plant.  This poses the danger of release of radioactive materials into the atmosphere and subsequent exposure to the people living near the damaged plant.  You may have heard on the continuous news coverage of this catastrophe that medical personnel are providing potassium iodine to people at risk for radiation exposure.

Why is potassium iodine useful for protection against radiation toxicity?  To answer this question we first need to discuss the thyroid gland.  The thyroid gland produces thyroid hormone which is released into the circulation to regulate metabolism of cells throughout the body.  Cellular metabolism generates body heat and energy utilization.  Thyroid hormone contains iodide and without iodide there is not thyroid hormone and this disrupts normal cell metabolism.  Normally iodine comes from dietary sources (including iodized salt) and this is sufficient to maintain normal thyroid function.  One of the toxic substances released from a damaged nuclear reactor is radioactive iodine.  When people breathe in radioactive iodine contaminated air, they are giving themselves a dose of this toxic substance.  Radioactive iodine accumulates in high concentrations in the thyroid gland and the radiation can then damage the thyroid or cause thyroid cancer.  IOSAT Photo

Interestingly, radioactive iodine is used to treat thyroid cancer as the radiation will kill off the tumor cells and iodine accumulates in the thyroid gland.  Anyway, people who are at risk will be protected against accumulation of radioactive iodine in the thyroid gland by potassium iodine supplements.  Potassium iodine fills up the thyroid stores of iodine leaving no room for radioactive iodine to accumulate.  Because potassium iodine is safe and non-toxic, there is no risk to using this preventative treatment.

Let’s hope that there is a quick and uneventful resolution to the current nuclear danger in Japan.  In the meantime, supplements of potassium iodine will help reduce the long term risks of exposure to any leaking radiation.

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