lorazepam

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n0mad

n0mad

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hi all, i have another question in pharmacology..

lorazepam is a benzodiazepine, which is extensively
metabolized in the liver.. but the majority of its metabolites
are inactive... so why is it that lorazepam is widely used?
i mean when you take a drug, you want the drug to be
active in the body, otherwise the drug is useless.. and yet
lorazepam is mostly inactivated by metabolism.. so should
it not be that lorazepam is not a potent drug? or is it that
the small amount of the active metabolite is sufficient to
do the job? to be potent?
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n0mad said:
hi all, i have another question in pharmacology..

lorazepam is a benzodiazepine, which is extensively
metabolized in the liver.. but the majority of its metabolites
are inactive... so why is it that lorazepam is widely used?
i mean when you take a drug, you want the drug to be
active in the body, otherwise the drug is useless.. and yet
lorazepam is mostly inactivated by metabolism.. so should
it not be that lorazepam is not a potent drug? or is it that
the small amount of the active metabolite is sufficient to
do the job? to be potent?
Click to expand...

Lorazepam does not need to be activated by the liver. Nor does oxazepam or temazepam - hence their extensive use in the elderly.

BenzoMetabolism.jpg


This is my favorite diagram for benzo metabolism.
 
Last edited:
n0mad said:
hi all, i have another question in pharmacology..

lorazepam is a benzodiazepine, which is extensively
metabolized in the liver.. but the majority of its metabolites
are inactive... so why is it that lorazepam is widely used?
Click to expand...

Lorazepam is extensively metabolized via hepatic mechanisms, but it is not rapidly metabolized, therefore, the drug has a very long plasma half life.
 
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It also appears to be the drug of choice (over diazepam) for controlling
status epilepticus. It tends to be less lipophilic so it stays in the CNS longer where diazepam has a tendency to migrate to more lipophilic portions of the body.
 
thats a fabulous diagram!
 
Drugs metabolized solely by Phase I mechanisms tend to require a change in dose with age as hepatic blood flow/liver mass/etc decrease (thus decreasing exposure to metabolic enzymes). Metabolism of these drugs generally slows down.

However, drugs metabolized by Phase II metabolism (e.g., glucuronidation) are relatively unaffected by changes due to age and are much less likely to require a change in dose in the elderly (from a PK standpoint, at least). Hence, the preference for using benzos like lorazepam and oxazepam in that population.

HTH.
 
n0mad said:
hi all, i have another question in pharmacology..

lorazepam is a benzodiazepine, which is extensively
metabolized in the liver.. but the majority of its metabolites
are inactive... so why is it that lorazepam is widely used?
i mean when you take a drug, you want the drug to be
active in the body, otherwise the drug is useless.. and yet
lorazepam is mostly inactivated by metabolism.. so should
it not be that lorazepam is not a potent drug? or is it that
the small amount of the active metabolite is sufficient to
do the job? to be potent?
Click to expand...

Inactive metabolites = granny doesn't fall and break her hip when she attempts to get out of bed the next morning. this can be a good thing :D
 
Priapism321 said:
Lorazepam is extensively metabolized via hepatic mechanisms, but it is not rapidly metabolized, therefore, the drug has a very long plasma half life.
Click to expand...


to reach the plasma, the drug must first bypass liver metabolism..
and since its extensively metabolized in the liver, what you expect
in the plasma is mostly inactive metabolites.. so im still wondering
how the inactive metabolites work.. its inactive after all... =' )
 
Parsox said:
It also appears to be the drug of choice (over diazepam) for controlling
status epilepticus. It tends to be less lipophilic so it stays in the CNS longer where diazepam has a tendency to migrate to more lipophilic portions of the body.
Click to expand...

when it migrates, its still migrating as an inactive form.. so what
good is migrating if its an inactive metabolite? what im trying to
understand is just that.. the drug is extensively metabolized in
the liver to an inactive form.. so how does that inactive metabolite
do the job? i mean if its inactive that means it doesnt do the job right?

i hope someone understand where im coming from.. :D
 
n0mad said:
to reach the plasma, the drug must first bypass liver metabolism..
and since its extensively metabolized in the liver, what you expect
in the plasma is mostly inactive metabolites.. so im still wondering
how the inactive metabolites work.. its inactive after all... =' )
Click to expand...

Not when given intravenously; have you actually studied the pharmacokinetics of parenterally administered lorazepam sport? You are coming off as someone who doesn't know much yet you continue to imply that you know something. You keep asking a question but refuse to accept anything that is not the answer you would like to hear. This is annoying. Lorazepam's plasma half life is somewhere in the neighborhood of 10-20 hours (ie, this is before all of the extensive metabolism you keep droning on about occurs).
 
n0mad said:
when it migrates, its still migrating as an inactive form.. so what
good is migrating if its an inactive metabolite? what im trying to
understand is just that.. the drug is extensively metabolized in
the liver to an inactive form.. so how does that inactive metabolite
do the job? i mean if its inactive that means it doesnt do the job right?

i hope someone understand where im coming from.. :D
Click to expand...

And, when given orally, the drug is 90% bioavailable, meaning that it IS NOT subject to FIRST PASS METABOLISM. So, once again sport, while lorazepam is extensively metabolized via hepatic mechanisms, this metabolism does not occur as the drug passes through the gastrointestinal tract on its way to the blood stream.

I feel like I said that already in this thread.
 
Priapism321 said:
Not when given intravenously; have you actually studied the pharmacokinetics of parenterally administered lorazepam sport?
Click to expand...

Priapism321 said:
And, when given orally, the drug is 90% bioavailable, meaning that it IS NOT subject to FIRST PASS METABOLISM. So, once again sport, while lorazepam is extensively metabolized via hepatic mechanisms, this metabolism does not occur as the drug passes through the gastrointestinal tract on its way to the blood stream.

I feel like I said that already in this thread.
Click to expand...


[youtube]http://www.youtube.com/watch?v=VqkN8XsYtJI[/youtube]

Anyways, to summarize all this in other words is that the extensive metabolism of lorazepam does not have much of a pharmacodynamic relevance. It's much more, pharmacokinetic with regards to its clearance.
 
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Priapism321 said:
Not when given intravenously; have you actually studied the pharmacokinetics of parenterally administered lorazepam sport? You are coming off as someone who doesn't know much yet you continue to imply that you know something.
Click to expand...

Yeah, and you are coming off as a douche, sport.
 
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worried about metabolism? Give it as a continuous infusion for ICU sedation.
 
ItsOverZyvox said:
lol
Click to expand...

Would you like me to open a can of worms? We should just get rid of lorazepam, it increases the incidence of ICU delirium and coma. Let's get the dexmedetomidine started!!
 
ya, all been said, BUT NICE DIAGRAM!! that wouldve helped a lot back then... :s
 
Priapism321 said:
Would you like me to open a can of worms? We should just get rid of lorazepam, it increases the incidence of ICU delirium and coma. Let's get the dexmedetomidine started!!
Click to expand...

I will kill you.
 
Pharmacokinetics blah blah blah.......From a retail perspective the junkies prefer Clonazepam...Teva brand mind you because it gives a much cleaner high with less of a morning hang over as the others. Oh yeah Watson estazolam does not work at all!!!

Nice diagram......
 
Parsox said:
I suppose we should afford that common courtesy. Good call. The question is do we sedate before we intubate or just paralyze then do it. Probably won't like us to mush of we do the later
Click to expand...

etomidate, then succ, then intubate. duh.


we use quite a bit of dexmetomidine in our neuro ICU - I gather it's better for arousing them to do neuro exams than lorazepam. A friend is doing her drug info paper on dexmetomidine and time to un-intubation.

I'm doing mine on T3 in cardiopulmonary bypass.
 
njac said:
etomidate, then succ, then intubate. duh.


we use quite a bit of dexmetomidine in our neuro ICU - I gather it's better for arousing them to do neuro exams than lorazepam. A friend is doing her drug info paper on dexmetomidine and time to un-intubation.

I'm doing mine on T3 in cardiopulmonary bypass.
Click to expand...

geek
 
njac said:
we use quite a bit of dexmetomidine in our neuro ICU - I gather it's better for arousing them to do neuro exams than lorazepam. A friend is doing her drug info paper on dexmetomidine and time to un-intubation.
Click to expand...

That's because they're awake the whole damn time, in excruciating pain, remembering the entire experience. For me, no thanks, give me the drug that produces anterograde amnesia while I am in the ICU. You give dexmedetomidine and the patient's require boat loads of fentanyl. Big surprise.
 
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Priapism321 said:
That's because they're awake the whole damn time, in excruciating pain, remembering the entire experience. For me, no thanks, give me the drug that produces anterograde amnesia while I am in the ICU. You give dexmedetomidine and the patient's require boat loads of fentanyl. Big surprise.
Click to expand...

I choose Priapism's approach. A little retrograde amnesia is good for the soul...
 
Can this be your new avatar? It suits you. :p

Univ%20of%20Miami%20Hurricanes%20Fanatic%20Doll.jpg


:smuggrin:
 
It was a nice, innocent suggestion. :smuggrin:

We can talk about lorazepam all day long... Old ladies get it by the bottle full. I'm pretty sure it's difficult to sleep when you're pushing 90!
 
Closing this thread. Lorazepam has been discussed 'ad nauseum' (no pun intended wrt Lorazepam side effects)

And just a reminder that insulting other members is not tolerable discourse.

Thanks folks.
 
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