General anasthetics

What is the mechanism of action of general anasthetics??

I can't find a decent explanation for their action so would appreciate any help.

Thanks...

Reply 1

Wangers

Some compete for parasynpathetic post synaptic receptor binding sites - permanently causing hyperpolerisation.

Others open alternate Na+ channels and thus disrupt nerve impulses. Some permanently block Tropmyosin Calcium sites. Some block myosin binding sites on the actin.

There are loads of others - those are the ones I know...

Reply 2

Revenged

Wangers

I asked about general anasthetics - not neuromuscular junction blockers...

Reply 3

pwofessow

Truth is: No one knows how they work..some ideas going about, but it still amazes me how people can use soemthing without knowing its mechanism of action.

The Lipid theory (which is not considered as useful as it used to be) states that anaesthetic moelcules enter the cell membrane and alter its 'fluidity' or volume, hence changing the function of the membrane.

The other idea is that the molecules interact with membrane proteins, either inhibiting excitatory receptors (e.g. acetelycholine, glutamate etc.) or enhancing the effects of inhibitory receptors (e.g. GABA)

None of them are, as far as I am aware, fully able to link the properties of the molecules with their actions.

Reply 4

Revenged

pwofessow

Ok... thanks for that...

I know that intravenous barbituates (e.g. thiopentone) act like benziodiazepines to inhance the action of GABA-A receptors... but that was about all...

How about the pharmacokinetics of the drugs... am I right in thinking that both the inhaled and intravenous anasthetics are lipid soluble and are rapidly carried into the blood to the central nervous system... and that they somehow inhibit activity of most of the neurones there?...

but if they do this... why is it that you lose consciousness whilst being about to breathe, pump blood around, maintain blood pH...etc.

Reply 5

Revenged

It is all a bit confusing... From my notes...

"The rate at which anaesthetics are absorbed is quicker for less-soluble agents."

How is that meant to make sense!

Reply 6

Wangers

just as a guess - they'll interact with water - which is polar and break up - maybe excreated? whereas is nonpolar they are absorbed and stored through lipid diffusion?? just as a guess.

Reply 7

pwofessow

Revenged

How about the pharmacokinetics of the drugs... am I right in thinking that both the inhaled and intravenous anasthetics are lipid soluble and are rapidly carried into the blood to the central nervous system... and that they somehow inhibit activity of most of the neurones there?...

but if they do this... why is it that you lose consciousness whilst being about to breathe, pump blood around, maintain blood pH...etc.

Anaesthetics have a wide range of solubility (in fat). Some are extremely soluble (halothane,e.g.), whilst others not so (Nitrous oxide). I'm sure you could find a table of anaesthetics and their oil:gas partition coefficient somewhere online.
I'm not sure about your last question. As far as I'm aware, anaesthetics depress the activity of most areas of the brain, having a stronger effect on the hippocampus, thalamus and the deep cortical layers into which the thalamus projects, i.e. the brainstem is 'relatively' less affected, hence it somewhat maintains the most important homeostatic reflexes (thou even these will become further depressed as the concentration of anaesthetics is increased, therefore necessitating a careful monitoring of the patient's condition..or even requiring active treatment, e.g. external ventilation or the odd drug or 2 to increase the heart rate).

Revenged

It is all a bit confusing... From my notes...

"The rate at which anaesthetics are absorbed is quicker for less-soluble agents."

How is that meant to make sense!

If the agent has a low blood solubility, then yes. For an agent to have a quick induction, a lower blood solubility will mean a quicker equilibrium time between alveoli and arterial blood, hence achieving the desired partial pressure quicker.

Reply 8

Revenged

I'm not sure about your last question. As far as I'm aware, anaesthetics depress the activity of most areas of the brain, having a stronger effect on the hippocampus, thalamus and the deep cortical layers into which the thalamus projects, i.e. the brainstem is 'relatively' less affected, hence it somewhat maintains the most important homeostatic reflexes (thou even these will become further depressed as the concentration of anaesthetics is increased, therefore necessitating a careful monitoring of the patient's condition..or even requiring active treatment, e.g. external ventilation or the odd drug or 2 to increase the heart rate).

Yes, that makes sense... The therapeutic index for anasthetics is very narrow... and if you give to much it probably causes respiratory depression due to it affecting the brainstem...

Ok, I see... Never would have worked out that myself... So thanks...

Btw, how is uni going?

which med school are you at btw... cuz if you are at ucl you probably know me... :p:

Reply 9

pwofessow

You're welcome.
I got exams coming up in 2 weeks, completely dreading it. It's just the sheer volume and the short revision period that's making me rather anxious. We're finishing up the respiratory system next week, and getting a week break before the exams, and they still expect us to be prepared for ward rounds and communication skills.
I guess it's the same with a lot of other med schools. I was under the (false) impression that 2nd yr would be easier than first (in my defence, that's what all the former 2nd yrs said!)

I'm in a place far far away, where people have a close relationship with sheep (or so I've heard) :p:

Reply 10

Revenged

i also have exams coming up but not for another four weeks... but my half year exams don't actually count, which is why i don't really care about them...

i think med schools do have their differences... I did respiratory system in the first year and have just finished a seven week module of neuro (which is perhaps more than you had)... and have never been on a ward round before...

i have to say wrt to exams... i did find the first year very stressful with the exams... simply because i had no idea how to prepare for them... and there is this 3 hour hellish paper that most people fail in, the rest of it is easy and few people fail in them - T and F papers, matching questions, anatomy spotter and a practical paper... to put it into perspective, in the second year last year the average mark for this hell paper was 52% (and considering a pass is supposed to be 50%) it does explain why so many people have to retake...

it is about techinque and learning to jump through hoops... i'm not that bothered about the nitty gritty details about anything anymore... the tactics this year are to question spot, learn all the airy fairy nonsense that i didn't bother with last year (communication skills, health promotion...etc.) and just get a broad overview of the hard stuff like anatomy... tbh with you, i used to be paranoid about the exams last year but i'm actually a bit bored of doing exams now - the entire year feels like a preparation exercise for the end of year exams... i'd prefer it if i had a little bit of scope to do what i'm interested in but all i feel that i've achieved in one and a half years is how to hoop jump...

Reply 11

pwofessow

Revenged

i also have exams coming up but not for another four weeks... but are half-years are only practice that don't count and so i don't really care about them...

i don't think med schools do have their differences... I did respiratory system in the first year and have just finished a seven week module of neuro (which is perhaps more than you had)... and have never been on a ward round before...

i have to say wrt to exams... i did find the first year very stressful with the exams... simply because i had no idea how to prepare for them... and there is this 3 hour hellish paper that most people fail in, the rest of it is easy and few people fail in them - T and F papers, matching questions, anatomy spotter and a practical paper... to put it into perspective, in the second year last year the average mark for this hell paper was 52% (and considering a pass is supposed to be 50%) it does explain why so many people have to retake...

it is about techinque and learning to jump through hoops... i'm not that bothered about the nitty gritty details about anything anymore... the tactics this year are to question spot, learn all the airy fairy nonsense that i didn't bother with last year (communication skills, health promotion...etc.) and just get a broad overview of the hard stuff like anatomy... tbh with you, i used to be paranoid about the exams last year but i'm actually a bit bored of doing exams now - the entire year feels like a preparation exercise for the end of year... i'd prefer it if i had a little bit of scope to do what i'm interested in but all i feel that i've achieved in one and a half years is how to hoop jump...

Guess we got a different system. Our half year exams actually do count. They will be weighed in, which is I guess a good thing. Means I don't have to learn everything I did this year for the exams in June :biggrin:

7 week neuro? So that includes normal anatomy, physiology and the major pathologies? Our system is different. Pathology and normality are divided between first and 2nd/3rd year. 1st yr is all about normal physiology and anatomy. We had a 3 week session about the brain and a 2 week session about nerves. In addition we had anatomy of the brain for another 2 weeks. I'm guessing this year we'll have another 2-3 weeks of brain patholgy.

I take it UCL are keen on students having a real deep understanding of the body before letting them go on wards then?

Our exams in first year were mainly MCQS and MEQs. Anatomy was fun actually: overall 100 questions, i.e. 100 stations, one minute to answer each question. Most tables had specimens on them, pointing at a nerve, muscle etc and we were required to identify it or answer a question about it.

I'm surprised you haven't been on ward rounds. Eventhou most of ours had no relationship with our lectures, I think most people have gained a lot more out of them than lectures. Are you guys doing clinical skills?

Reply 12

Revenged

pwofessow

I take it UCL are keen on students having a real deep understanding of the body before letting them go on wards then?

I'm surprised you haven't been on ward rounds. Eventhou most of ours had no relationship with our lectures, I think most people have gained a lot more out of them than lectures. Are you guys doing clinical skills?

Yes, we do have clincal skills... We get a 5th year and a someone is paid to come in so we can do an examination on them... It is a really good way to learn... We were testing the lower motor system - "In the pouring rain she came graciously" - Inspection, Tone, Power, Reflexes, (Sensory), Coordination, Gait...

but I did go on the wards once... but that my one and only time I've been in UCH...

7 weeks neuro was two weeks head and neck anatomy and five weeks was neuroanatomy, neuroscience and various other things... but let's not get into that... i'm just glad its over...

Reply 13

Revenged

I was just wanted to check if I understood these graphs...

The graph on the left is about inhallation anasthetics...

Nitric oxide:

- Low potency (minimum alveolar concentration is low)

- Graph shows that low potent anasthetics are more quickly absorbed into the blood

Halothane:

- High potency (minimum alveolar concentration is high)

- Graph shows that high potenet anasthetics are more slowly absorbed into the blood

I'm still a bit confused why tbh...

I don't really understand what the blood/gas coeffiecient is...

Anyway, there is another graph on the right, which is about intravenous anasthetics...

I'm not too sure what the graph is supposed to show... It is saying that anasthetic goes from the blood to the brain and then into other tissues and fat... but what is the significance of this?...

scan0001.jpg227.1KB

Reply 14

pwofessow

Revenged

A few basic concepts first:
1) Potency is related to fat solubility ,i.e. the oil:gas partition coefficient. The higher the solubility, the more potent the anaesthetic, hence why Nitric oxide has a low potency. (fat solubility also has an effect on recovery..more on it later)
2) The main factor determining induction/recovery (to an extent for recovery) is the blood:gas partition coefficient (i.e solubility in blood, I think I mentioned it a few posts before)

I got the following values for nitric oxide: blood:gas=0.5, oil:gas=1.4...and for Halothane: blood:gas=2.4 and oil:gas=220.

From those values, you can see why nitric oxide is absorbed quicker than Halothane (the lower the blood:gas coeffficient, the quicker the absorption), and why its potency is lower.

The second graph would also be the same for inhaled anaesthetics. It shows the transfer of anaesthetics to the different tissue. The significance here relates to recovery. Imagine I give someone nitric oxide--> quick induction, but low potency. It will travel to the brain, which is where it'll have its main effect. Due to it's low fat solubility, its accumulation in fat tissue is less significant (which is what happens as time passes). Fat has a low blood flow, therefore if anaesthetics were to accumulate here, it'll take significantly longer to recover (i.e. get rid of the anaesthetic agent).

If I gave someone Halothane, which has a high lipid solubility..well you can imagine that a significant portion will accumulate in fat tissues, and even when you stop supplying the patient with the anaesthetic, the patient will still have a 'reservoir' of anaesthetic in his fat tissue and still experience the effects, hence delaying recovery.

Reply 15

Revenged

Ok... I think I've finally got it but I want to check...

Nitrous oxide has a fast induction time because it is absorbed quickly into the blood... and it also has a fast recovery time because it has low fat solubility and so is not stored long in fat stores... but it has a low potency because it is not very fat soluble and you need to give a lot of it...

Halothane has a slow induction time becuase it is slowly absorbed into the blood and it also has a slow recovery time because it has a high fat solubility and it is stored in fat for a long time... but it is very potent (because it is very fat soluble) and so you do not need to give a lot of it to have an effect...

NB. Btw, it is nitrous oxide (N2O) and not nitric oxide (NO)... I got them confused as well...