1. General Anesthetic Drugs Pt. I Flashcards
Path of Anesthetic Gas
Mask -> pulmonary alveoli bood -> brain or metabolism
• The gaseous agents or volatile liquids have to get into the CNS
• These drugs behave by pressure gradients so it has to saturate one system to get into
another. So it has to saturate the ____ space, then the ____, for it to jump into the
CNS.
• There are (metabolic) breakdown products for some of the ____ but there are no breakdown products for ____ (nitrous)
alveolar
blood
halogenated hydrocarbons
N2O
- After inhaling the anesthetic gas, some of the molecules will dissolve in the alveoli, saturate the system, and then bubble out of solution and jump into the ____.
- It would take a certain amount of molecules to saturate the blood compartment and then it can jump into the CNS. Obviously we are talking about ____ that surround the brain
- We can come up with a value called the blood/gas partition coefficient and it is basically the number of molecules to saturate the ____ compartment over the number of molecules it takes to saturate the ____. Here you can see that it took 12 molecules in the blood and six in the lungs. So 12 divided by 6 is 2 (He was counting the dissolved molecules).
• So how is this done scientifically? They will fill a flask up 2/3rds full with blood and the rest with air and pump the general anesthetic gas in and shake it. They then look how much is in the blood and how much is in the air.
blood vessels
blood vessels
blood
lungs
When speaking about gaseous anesthetics (volatile liquids):
• Only anesthetic molecules in ____ phase move from compartment to compartment
• Those general anesthetics that are least soluble in blood saturate the blood ____
– ____ blood solubility = increased onset time and increased offset time
– ____ blood solubility = decreased onset time and decreased offset time (i.e. they come on ____ and have a ____ duration)
gaseous
quicker
increased
decreased
quicker
shorter
Very much like halothane or enflurane.
Onset = ____ minutes
Blood/Gas partition coefficient = 12/6 = ____
Anesthetic gases are liquid in room temperature but are heated up so the patient can breathe in the fumes
• Halothane or enflurane, with a blood gas coefficient of about 2, takes 3-5 mins to put a patient to sleep
• If we compare that with anesthetic gases with even lower solubility …
3-5
2
Very much like N2O or desflurane.
Onset time = ____ minutes
Blood/Gas partition coefficient = 3/6 = ____
Now it takes 6 to saturate the lung compartment but only 3 molecules to saturate the blood and bubble out. (FYI he keeps the number 6 for simplicity). Your blood gas solubility coefficient would be 0.5
If this was shaken in a flask there would be very little in the ____ and more in the ____ phase.
The anesthetics that behave like this are N2O. Now N2O is really for the onset for sedation, not general anesthesia because the MAC (Minimum Alveolar Concentration AKA ED50-effective dose to put people asleep) is over ____%. This means ____% oxygen (not possible).
You will start catching a buzz from this really quick because it has really low blood gas solubility AKA a low blood gas partition coefficient.
If you take off that N2O it typically takes only a couple of minutes for that patient to recover. Why? Because of the ____ blood gas solubility.
It turns out that desflurane and sevoflurane behave like N2O also. Although their blood gas coefficient are a bit higher, so they take a little longer to work, they are powerful enough to put people asleep with plenty of ____
1-2
0.5
blood
air
100
0
low
oxygen
Very much like ether
or methoxyflurane Onset time = ____ min
Blood/Gas partition coefficient = 78/6 = ____
• This is how Methoxyflurane and ether (no longer used anymore) behaves
• It takes 6 molecules to saturate the alveoli but now the blood is going to take a while to
saturate.
• There are now 78 blue dots in the blood vessel
• The blood gas solubility coefficient is going to be really high. This anesthetic is very
soluble in the blood and takes a long time to ____, come on, and wear off.
• This is why Guedel was able to see all those stages of anesthesia because it ____
progressed and he could see these things where it harder to see with the more rapidly
progressing agents.
• In the real world of anesthesia they give you a bolus of ____ or fentanyl or midazolam and blast you out in 15 secs and then they maintain you with the ____ with the occasional squirts of the IV agent
• Side conversation about his colonoscopy. (Probably not important: at Radnor their SOP is propofol without intubation. At Penn they use Fetnyl and midazolam and sometimes propofol)
15-20
13
saturate
propofol
general anesthetic gas
Ways to speed up onset of anesthetic gas?
• Increase ____ of gas inhaled.
• Increase ____ ventilation.
• Combine slower acting agent with more ____ acting agent (one with a lower blood/gas solubility coefficient). Typically that more rapidly acting agent is ____.
concentration
pulmonary
rapidly
N2O
Properties of Inhalation Anesthetics
• As the blood gas partition coefficient increases, so does the ____ time.
• It also takes longer to clear this stuff
• There is another coefficient that is important for general anesthetic gases and thats
what people call the “____ partition coefficient”. The general principle here is that the ____ lipid soluble the anesthetic gas, the ____ you need for a MAC.
• These numbers vary depending on the articles and they dont all work out but basically increasing lipid solubility lowers the ED50 or the ____
- Whats the problem with nitrous? It is so “unlipid” soluble that you need more than 100%
- Side conversation about the theory that Einstein got information from Aliens and the recent news about the black hole
- Other than nitrous they all have MACs where you can give plenty of ____ and induce general anesthesia
- Now, remember MAC is ____ where 50% of people respond at that dose or lower than that dose.
- When giving a dose in real practice do you want to give at MAC? No, because it only works on ____ of the individuals
- These agents other than nitrous have really steep dose response curves. So once you have 1.3XMAC now you have ____ (almost everyone falls asleep)
onset
fat blood/water
more
less
MAC
oxygen
ED50
half
ED99.9
Anesthetic Gas Potency
• Potency directly parallels ____ solubility
• MAC = minimal alveolar concentration
– Not the big
Definition = That concentration of a gaseous or volatile liquid anesthetic agent in which 50% of patients don’t respond to a surgical ____. MAC is really an ____ or median effective dose.
lipid
stimulus
ED50
As lipid solubility (potency) increases MAC ____. Potency is more important with ____ (volatile) anesthetics than
other drugs you have heard about in pharmacology. Why?
Anesthetic must
be potent enough to be able to supply patient with adequate concentration of ____.
decreases
gaseous
oxygen
Properties of Inhalation Anesthetics
- There is no relationship between ____ coefficients and MAC. Or in other words there is no relationship between the onset time and how ____ soluble the general anesthetic is.
- If you at one of the most lipid soluble, methoxyflurane, it has a low MAC but it takes a ____ time to come on. Though most often they are ____ if you look at the numbers
blood gas solubility
lipid
long
opposite
Important Principles
- By combining a ____ like halothane with N2O you lower the MAC of each agent, especially the more ____ one (in this case halothane).
- Normally halothane MAC = 0.8%
- When combined with 60% N2O, MAC of halothane = ____% and you can still give plenty of oxygen with the combo
- ____ anesthetics also lower the MAC of gaseous anesthetics like halothane
halogenated hydrocarbon
toxic
0.8
intravenous
Where do general anesthetics work?
Also ____ horn.
____ centers
Ascending ____
spinal and medullary dorsal
subcortical
RAS
Where do general anesthetics works?
There are a bunch of studies out there that show that if you take out wisdom teeth under general anesthesia and compare it to people who also had local anesthesia, the people that got local consumed less post operative analgesics. Maybe some of the sensory input is going through and causing a phenomenon known as “____” or where the brain gets wound up from these pain signals and puts the brain into a prolonged pain state.
The other place where some of the agents may be working is in the ____ of the medulla/spinal cord, analogous what opioids do, blocking the release of substance P and excitatory amino acids
There are a couple of studies that show that some of nitrous’s activity (has good analgesic effects) is naloxone ____. This gives you a hint that maybe part of nitrous’s action is in
the release of endogenous ____ like enkephalins in the dorsal horn. This would decrease the release of pain provoking neurotransmitters
central sensitization
dorsal horn
reversible
opioids
General anesthetic mechanisms on a molecular level may have some similarities to local anesthetics.
____ Channel Blockade
Membrane ____
sodium
expansion
