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SkyARKy t1_jef4h4o wrote

Benzos have a limit to their function. They depend on a neurotransmitter called GABA which is a CNS depressant. Once GABA is depleted then any additional Benzos will have no effect, therefore no overdose. Unfortunately, if you compound this effect with other depressants (who operate on a different mechanism) you can get respiratory depression which can be fatal.


Youwillgotosleep_ t1_jeflcph wrote

As someone with a working knowledge of pharmacology and anesthesia, this right here.

Edited for terminology and corrections: The GABA receptor has a maximum effect that can be elicited from benzos. Once the receptors on it are bound by benzos there can be no further action, a ceiling effect. When other substances are added such as alcohol and narcotics they cause respiratory depression by means of other receptors, in the case of narcotics the opioid receptors, mu, kappa and delta. In the case of alcohol it ties up a different receptor on the same GABA neurotransmitter so it potentiates the effects caused by GABA activation. Other substances can also have the same effect as alcohol. This is essentially what happened to Anna Nicole Smith.


anvuu t1_jegmtti wrote

Is that why in status seizures - once we hit the midazolam ceiling there's no point giving more and use another drug?


Youwillgotosleep_ t1_jegogd7 wrote

I’m not familiar with this particular treatment but drugs are only so effective. Once you hit a particular concentration you are no longer getting meds to the appropriate receptors since they are saturated. Additional medication will just cause side effects since increased concentrations of drugs will just start causing side effects by interacting on other receptors. Using a different medication allows you to get the same action but without the increased drug concentrations.


j_ohnsonson t1_jegr22o wrote

I believe that Is tied to the fact that when a status epilepticus goes on for some time, the GABA receptors start being pulled away (in a process called endocytosis) from the synapses. So You Need to rely on drugs that use other mechanisms to get the neurons to stop firing. Happy to be corrected if someone has more up to date or precise info


WarriorNat t1_jeh4nol wrote

This must be why in the hospital we can give such high doses of benzos to people in alcohol withdrawal with so little risk. I know they mimic the effect of alcohol for people who drink around the clock, but it still feels crazy giving 4mg lorazepam every hour (often with little effect) when most of us would get 8 hours sleep on 0.5mg


Llohr t1_jegrghn wrote

I'd like to add to this: While benzos on their own are rarely fatal if overdosed, withdrawal from them is one of the most dangerous forms of withdrawal, and can itself be fatal.

I've known some people who would read that they're so rarely fatal high doses and think, "wow I can take all the benzos I want! Benzos are safe!"


werq34ac t1_jegsm89 wrote

Also adding to this, Flumazenil is basically the Narcan of benzos, and can reverse benzo overdose. We basically never use it because it can easily send someone into status epilepticus whilst simultaneously rendering the first-line treatment of status epilepticus (benzos) completely ineffective.


Terribletwoes t1_jegvqlu wrote

To add, correct, or be pedantic:

Benzos increase the frequency or likelihood of an inhibitory chloride channel opening. Barbiturates open it.

This is why barbiturate overdoses are far more likely than benzos to result in death - unless another sedative agent is added like alcohol or narcotics. And why we can induce general anesthesia with barbiturates but rarely benzos alone.

-Peds gas passer