Benzodiazepine dosages

[Diana]

I am currently writing a report (in a jounalistic sense) regarding 'feelgood doctors', using celebrity cases that have been reported in the media. I would like some clarity on benzodiazepine doses and their effects on the body and also tolerance. The example i am using is a recognised case that is currently reported on in the media. The following information is public knowledge and the focus of my query.

The following was administered to the patient -

1.30 am - 10mg valium (liquid)
2.00 am - 2mg lorazepam (liquid)
3.00 am - 2mg midazolam (liquid)
5.00 am - 2mg lorazepam (liquid)
7.30 am - 2mg midazolam (liquid)

(1)After the complete administration of these drugs, would you expect the patient to awake or asleep, assuming there is no tolerance?

(2)If asleep, how deeply sedated would you expect the patient to be after the complete administration of those drugs? Also, how sedated would the person be at the separate time intervals shown above?

(3)Are the individual doses given for each drug larger than what you would normally give or within the normal range? What is a 'normal' dose for each of the above drugs, and what effect would the normal dose have on the body?

(4)Under what circumstances would a person be awake after the complete administration of those drugs? If the person is awake, does this imply they are tolerant to those drugs?

(5)If a person is tolerant to lorazepam, for example, and took a large dose that they could cope with, would you expect there to be a high level of the drug in the bloodstream (if a blood sample was taken) corresponding to the amount taken, or would the blood level be lower in a tolerant person because they can metabolize more efficiently? Can the blood level tell us anything about the tolerance capacity of that person?

[Sir_Dispensalot]

considering the tmie in the evening that i'm replying, i won't give a detailed answer (that and i can't be bothered trawling through all the reference texts). dose of benzos like lorazepam and midazolam are not just given for sedation. even if this case is 'well publicised' there could well be a good clinical reason for this prescribing regimen (for example in severe status epilepticus). some more background info may help us out without exonerating or condemning someone based simply on dry facts.

[Diana]

The medication was used only to try and induce sleep. Said person was an insomniac. The person had no health problems and was not ill at the time. The verdict on the doctor's performance here is not required (although it has been said by other professionals that no-one would mix drugs like that). If you could answer the 5 short q's i would be very grateful.

I live in lancashire too!

[johnep]

Sound a bit like Michael Jackson or Amy.
johnep

[LeftArm]

Benzodiazepines can cause paradoxical side effects.

[Diana]

It is about Michael Jackson obviously! But Amy who? I hope the fact it is Jackson will not prevent people from answering my questions.

[LeftArm]

The person had no health problems and was not ill at the time.

He looked a bit peaky to me.
He was addicted to Propofol a strong anaesthetic and was given 25mg of this after the Benzodiazepines you have already listed.

[johnep]

Midazolam is the 'forgetfulness' drug. I had it before a gastroscopy. Will induce sleep. Popular with anaesthetists as short acting.
Propofol is used for inducing anaesthesia, it replaced sodium pentobarbitone (pentothal).
It normally would not be used other than inducing agent or to sedate pt on a ventilator.
MJ quite out of any normal experience. AW still alive, used to be with Pete Docherty.
Anything we could tell you would really have no bearing in this case as right outside any normal therapeutic use.
johnep

[Sir_Dispensalot]

speaking in a purely speculative / hypothetical way then if mj had been a chronic user/abuser of benzodiazepines and other sedatives / hypnotics then he would require large and frequent doses to obtain a response. i found this article on google scholar:
ScienceDirect - Life Sciences : Benzodiazepine - specific and nonspecific tolerance following chronic flurazepam treatment

it's probably safe to assume that most benzo's act in a similar way - main mechanism of tolerance seems to be a downregulation of the cell receptor response to in this case flurazepam - in other words it's likely that blood levels of the benzo would remain high - it's just that larger and larger amounts of drug would be needed to activate cell receptors to the same level as a benzo-naive subject. it looks like some generalised tolerance develops too, so some metabolism of the drug would be increased but not to the same extent.

[Diana]

Yes the questions are purely speculative. I am not on the case! I know what the drugs do, as indicated in a drug book. What i am unfamiliar with are the specific doses, and whether they are considered normal or not, and what state a person 'may' be in after them being administered. These things have already been discussed in interviews on tv and written about. Professionals have commented. What i was looking for was a little more detail. I am trained in Cell Biology so can cope with the info on that level. I came here because i thought pharmacists might be able to help with my q's. If you feel it is not appropriate (for whatever reason) to answer i can ask a pharmacist face-to-face. If someone feels able to answer the q's point by point as listed above i would be grateful. If not, can someone let me know.

The propofol administered after the benzos is not my concern. That is not important to me here. I am well versed in the details of the AR and affidavit etc, so i am aware of everything else in terms of background info.