For barbiturates like methohexital, what determines onset of action?

For barbiturates like methohexital, what determines onset of action?

• A. Lipid solubility
• B. Ionization in blood
• C. Protein binding
• D. Hepatic extraction

Answer: (A)

The speed at which an IV anesthetic acts depends mostly on how quickly it reaches the brain, which is governed by how easily it dissolves in fats and crosses the blood–brain barrier. Methohexital is highly lipid soluble, so it rapidly penetrates the CNS and produces anesthesia within seconds—giving it a very rapid onset. Ionization in blood can influence membrane crossing to some extent, but the dominant factor determining how fast this drug starts working is its lipid solubility. Protein binding affects how long the drug stays around and where it redistributes, influencing duration and distribution more than the immediate onset. Hepatic extraction relates to how quickly the drug is cleared by the liver, shaping duration and recovery rather than initial onset.

The speed at which an IV anesthetic acts depends mostly on how quickly it reaches the brain, which is governed by how easily it dissolves in fats and crosses the blood–brain barrier. Methohexital is highly lipid soluble, so it rapidly penetrates the CNS and produces anesthesia within seconds—giving it a very rapid onset.

Ionization in blood can influence membrane crossing to some extent, but the dominant factor determining how fast this drug starts working is its lipid solubility. Protein binding affects how long the drug stays around and where it redistributes, influencing duration and distribution more than the immediate onset. Hepatic extraction relates to how quickly the drug is cleared by the liver, shaping duration and recovery rather than initial onset.