1. Less symmetrical ethers are more potent due to its decreased propensity to form peroxides
2. Halogenation decreases flammability and potency of ethers
3. At least one H-bond is needed for CNS depression
4. Successful anesthetics are fluorinated with one or two halogens; excessive halogenation may produce convulsions
5. Toxicity with substituents: I>Cl>Br>F
6. Potency with substituents: F>Br>Cl>I

Polar anesthetics have higher blood:gas partition coefficients, therefore require more agent for saturation.

Both saturation and removal after administration is slow; the agent is more likely to be metabolized.

Describe the mechanism of delivery for Non polar anesthetics.

Non-polar anesthetics have lower blood:gas partition coefficients, thus requiring less agent for saturation.

Saturation and removal after administration is rapid; the agent has less chance of metabolism, but more non-polarity raises the issue of sufficient delivery to the brain.

Advantages:

uses much less of the anesthetic

Fluorocarbon anesthetics are green house gases

Disadvantages:

Chemical reaction with calcium oxide may occur

chloroform was replaced by fluorinated compounds due to its hepatotoxicity.

True or False? and why?

The highest toxicity in inhaled anesthetics occurs with the very blood insoluble compounds.

False.

The highest toxicity occurs with the very blood SOLUBLE compounds such as methoxyflurane.

True or False? and why?

The more lipid soluble compounds such as desflurane experience very little metabolism.

True.

Halogenated compounds are metabolized less than the corresponding hydrogen-containing analogs.

Resistance to metabolism is in the order F>Cl>Br, thus fluorinated compounds are preferred.

What is the common toxic metabolite for Desflurane, Halothane, and Isoflurane?

Place the following in order of most to least toxic:

Halothane, Methoxyflurane, Enflurane, Sevflurane, Desflurane, Isoflurane, Xe, N2O

State why.

Xe<Des<N2O<Sev<Iso<En<Halo<<<Methoxy

This is based on the Blood/Gas partition coefficient at body temperature.

Desflurane

low blood solubility

Enflurane

low blood solubility

Etomidate

short acting anesthetic

R-isomer used clincially

GABA-ergic; ratio of potencies of the two isomers parallels their modulation of GABAa activity

halothane

somewhat blood soluble

first halogenated inhaled anesthetic

Isofurane

low blood solubility

Ketamine

causes unique cardiovascular stimulation via excitation of CNS.

Used as racemic mixture, but S enantiomer is more active

Targets Na/Ca channels controlled by NMDA and glutamate receptors

Methoxyflurane

Blood soluble. Hepatotoxic.

sevflurane

low blood solubility

caution use with recycling systems

Thiopental

High lipid solubility

xBBB and equilibrates in 1minute

Poorly water soluble

Almost totally metabolized at 12%/hour

Gives rapid induction but slow recovery