Youwillgotosleep_ t1_jeflcph wrote on March 31, 2023 at 5:29 PM

Reply to comment by SkyARKy in ELI5: If benzodiazepines are CNS depressants, why is it so hard to die from a overdose of them alone? by psychrolute

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.

phillyvanilly666 t1_jeg5x91 wrote on March 31, 2023 at 7:45 PM

Username checks out

Sammarg t1_jegkbp7 wrote on March 31, 2023 at 9:22 PM

*Mu, Kappa, Delta

Youwillgotosleep_ t1_jegn8is wrote on March 31, 2023 at 9:42 PM

Thanks for the correction

anvuu t1_jegmtti wrote on March 31, 2023 at 9:39 PM

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 on March 31, 2023 at 9:50 PM

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 on March 31, 2023 at 10:09 PM

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

MasterShoNuffTLD t1_jegnxrf wrote on March 31, 2023 at 9:47 PM

Potentates

WarriorNat t1_jeh4nol wrote on March 31, 2023 at 11:52 PM

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