Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Did Drugs Kill Whitney Houston

As with the death of Michael Jackson, this is not a call you want to be on, because everybody is going to be second-guessing everything that was done, but let’s assume that you are dispatched.

Law enforcement sources tell TMZ … multiple medicine bottles were found in the Beverly Hills hotel room where Whitney Houston died … but we’re told there were NOT a lot of pills at the scene.[1]

there were NOT a lot of pills at the scene.

This suggests that a lot of pills were taken, but does not tell us over what time period?

How many pills should have been in the containers if the pills were taken as prescribed?

Among the pills … ibuprofen (painkiller), Xanax (anti-depressant), Midol (for menstrual cramps), amoxicillin (for treating bacterial infections) … and more.[1]

Ibuprofen and Midol are sometimes the same thing, but Midol comes in so many different formulations, that you cannot tell without knowing the specific version.[2] I did not know there were so many different drugs sold under essentially the same name. Besides, I use chocolate to keep my inner woman from PMSing.

The ones that catch my eye are – . . . Xanax … and more.

What is Xanax?

Xanax is the brand name for alprazolam, a benzodiazepine. Other benzodiazepines are drugs we commonly carry – diazepam (Valium), midazolam (Versed), and lorazepam (Ativan). Treatment of benzodiazepine overdose is supportive care (maintain oxygenation and ventilation, and maintain blood pressure). There is a competitive antagonist, flumazenil (Romazicon), but flumazenil does not bring benzodiazepine overdoses back from the dead any more than naloxone (Narcan) brings heroin overdoses back from the dead. The treatment for opioid overdose is also supportive care.

Absorption
Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in 1 to 2 hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay methodology, the mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours (range: 6.3–26.9 hours) in healthy adults.
[3]

11+ hours can be a long time. Xanax XR (eXtended Release) does not appear to prolong the clearance of alprazolam, only the onset. What can affect the rate of elimination of alprazolam?

Metabolism/Elimination
Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam.
[3]

A lot of the technical drug information is not important, but the cytochrome P450 metabolism is important in the elimination of a lot of medications

CYP3A4 is a member of the cytochrome P450 superfamily of enzymes. . . . This enzyme is involved in the metabolism of approximately half the drugs that are used today, including acetaminophen, codeine, ciclosporin, diazepam, and erythromycin. . . . Most drugs undergo deactivation by CYP3A4, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYP3A4 to form their active compounds, and many protoxins being toxicated into their toxic forms[4]

Grapefruit juice can slow down metabolism by about half, so some consumer sites may recommend that people drink grapefruit juice to cut down on the cost of medications. This really is not a great idea, since it may affect other medications. It is something to discuss with a doctor, so that your doctor is aware of things that may interact with the medications you are taking, but doctors should do that anyway.

One interesting item that does not appear to be related to CYP3A4 metabolism. It makes me wonder about the effect flumazenil might have on smokers. There is no mention of smoking or cigarettes on the flumazenil label.[5]

Cigarette Smoking
Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.
[4]

We’re told some of the pills were old … some issued in 2011 … but some of the bottles were from 2012.[1]

As long as a month and a half ago? Some people have milk and eggs that are that old, too. The medications should age much better than dairy products.

A prescription for alprazolam is often written as PRN (Pro Re Nata – Latin for according to the circumstances, or to be taken as needed). Alprazolam is an anti-anxiety drug that has addiction potential, just as with other GABA (GammaAminoButyric Acid) agonists (such as benzodiazepines and alcohol).

A PRN prescription that is more than a month old is not a problem. A prescription that is empty too soon is much more likely to be a problem. One problem with PRN prescriptions is that we usually do not know how quickly the patient has been taking them, so we do not know how many should be in the pill bottle. Some people do not want others to know that they are taking medication to manage anxiety (Tony Soprano), so their family may not even know they have a prescription for these medications.

In other words, with PRN medications, it is difficult to determine if too much has been taken

The acute oral LD50 in rats is 331–2171 mg/kg. Other experiments in animals have indicated that cardiopulmonary collapse can occur following massive intravenous doses of alprazolam (over 195 mg/kg; 975 times the maximum recommended daily human dose of 10 mg/day).[3]

Prescriptions often come in a pill bottle that contains 100 pills of 0.5 mg, 1 mg, or 2 mg strengths. It is unlikely that a dose of even 200 mg would be enough by itself to kill a person.

General Treatment of Overdose
Overdosage reports with XANAX Tablets are limited. As in all cases of drug overdosage, respiration, pulse rate, and blood pressure should be monitored. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors. Dialysis is of limited value. As with the management of intentional overdosing with any drug, it should be borne in mind that multiple agents may have been ingested.
[3]

With any potential overdose, always assume that other drugs/poisons have been taken.

We should use the Plus One Rule

We should assume that there is at least one drug that we do not know about that the patient has taken. If we find out about more medication, wed still should assume that there is something that the patient has taken that we do not know about. The same rule applies to weapons. We should always assume that a violent/potentially violent patient has at least one weapon that we do not know about. Especially after they have been searched by police or prison personnel.

We should not expect antidotes to work the same way in dead patients as they do in living patients.[6]

General supportive measures should be employed, along with immediate gastric lavage.

Lavage (pumping the stomach) is not something EMS should be doing. Inducing vomiting is a bad idea in a patient who may not be able to protect her airway – even with an endotracheal tube in place.

Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors.

Always use fluids for hypotension before pressors, unless fluids are contraindicated, or unless a pressor is specifically indicated, even with acute CHF (Congestive Heart Failure).

Did drugs kill Whitney Houston?

I don’t know, but the drugs listed in this article probably did not kill her.

Footnotes:

[1] Whitney Houston – Few Pills Recovered at Death Scene
TMZ
2/13/2012 7:45 AM PST by TMZ Staff
Article

[2] Midol
Wikipedia
Article

As with cough and cold medicine, it is important to read the label to know what you are getting

The “Midol Complete” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Caffeine 60 mg (Stimulant)
Pyrilamine Maleate 15 mg (Antihistamine)

The “Extended Relief” formulation consists of:

Naproxen Sodium 220 mg (NSAID, Pain Reliever/Fever Reducer)

The “Teen” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Pamabrom 25 mg (Diuretic)

The “Liquid Gels” formulation consists of:

Ibuprofen 200 mg (Pain Reliever)

The “PM” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Diphenhydramine citrate 38 mg (Sedative antihistamine)

[3] XANAX (alprazolam) tablet
[Pharmacia and Upjohn Company]

DailyMed
NLM
FDA label

[4] CYP3A4
Wikipedia
Article

Large list of drugs that affect CYO3A4 metabolism.

[5] FLUMAZENIL injection, solution
[Baxter Healthcare Corporation]

DailyMed
NLM
FDA label

[6] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Rogue Medic
Tue, 01 Nov 2011
Article

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