Racemic Epi Question

[medicswag]

Hey Guys,

Could racemic epinephrine be "macgyvered" by mixing epi and NS in the appropriate amounts?


Thanks,
Rob

 

[NomadicMedic]

You can use regular epi 1:1000 in a neb to treat croup, but it's not "racemic" unless it's a 1:1 mix of D and L chiral molecules.

"Regular" epi is the levorotatory isomer, and studies have shown it works just as well, but it's a higher dose. (5mg Epi in 2-5ml of NS)


Sent from my iPhone.

 

[johnmedic]

I was recently told the same information, anecdotally without sources. Epi 1:1000 & NS = Homemade Racemic Epi. But can't find any real information on the topic. Read up on Racemic Mixtures & I'm sure that a on-the-fly mixing of NS&Epi isn't technically Racemic & I'm going to ask our MPD about 1:1000 in a neb for Croup. The issue being that it's not in our protocols while (even though most agencies don't carry it) Racemic Epi is.

More responses/info would be helpful!

 

[JPINFV]

It is chemically impossible to make a racemic mixture by taking a single enantiomer and adding normal saline, even if you shake it real hard.

 

[NomadicMedic]

It's not "homemade racemic epi", it's simply nebulized Epi in saline. As I said above, racemic Epi is Epi that has both a "left-handed" and "right-handed" isomer... Better explained as chirality.

You can't just dump Epi into saline and whip that up. Regular L-Epi works just fine when nebbed up for croup.

O-chem came in handy at last.


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[johnmedic]

It's not "homemade racemic epi", it's simply nebulized Epi in saline. As I said above, racemic Epi is Epi that has both a "left-handed" and "right-handed" isomer... Better explained as chirality.

You can't just dump Epi into saline and whip that up. Regular L-Epi works just fine when nebbed up for croup.

O-chem came in handy at last.


Sent from my iPhone.

Ohh okay sorry but your first post flew over my head.. with you restating as above (plus the couple episodes of Breaking Bad I've seen) it makes sense! I suppose that's what a coworker was trying to say, that nebulized epi will do the trick, while we don't carry R-Epi. Thank you!

 

[JPINFV]

To add to this, an enantiomer is a hydrocarbon molecule where at least one carbon molecule has 4 different side chains, thereby forming a tetrahedral 3d shape (VSEPR can kiss my ____). Depending on which side chains are where, will depend on whether it's a L enantiomer or a D enantiomer. A racemic mixture is a mixture of both L and D enantiomer.

Since adding normal saline cannot result in a structural change of epinephrine, it cannot convert a chiral mixture (i.e. a mixture with more L or D enantiomers than the other enantiomer) to a racemic (equal L and D enantiomers) mixture.

 

[NomadicMedic]

Haha. Okay. That was more than I could quote from my sketchy memory. (I actually only remembered the racemic bit because I had a chat with a co worker a few weeks ago...)

Another reason I love this forum.


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[medicswag]

To add to this, an enantiomer is a hydrocarbon molecule where at least one carbon molecule has 4 different side chains, thereby forming a tetrahedral 3d shape (VSEPR can kiss my ____). Depending on which side chains are where, will depend on whether it's a L enantiomer or a D enantiomer. A racemic mixture is a mixture of both L and D enantiomer.

Since adding normal saline cannot result in a structural change of epinephrine, it cannot convert a chiral mixture (i.e. a mixture with more L or D enantiomers than the other enantiomer) to a racemic (equal L and D enantiomers) mixture.

Right, but since the (+) stereo isomer is metabolically inert, would replacing it with water really change the character of the solution? Wouldn't a solution of (-) and (+) enantiomers be functionally equivalent to a solution of the l-isomer and normal saline?

The distinction between (-)/l and (+)/d is only the way in which they rotate plane polarized light. This distinction is naturally a result of their R/S stereochemistry, though R/S has no direct correlation to the molecules respective d or l designation.

I have always been under the impression that racemic epi is in fact racemic, only to save the cost of separating the enantiomers. Since they only differ in their arrangement in 3d space, they have the exact same physical properties, making them rather difficult and costly to purify.

So while yes, a mix of l-epi and NS would not by definition be racemic, would the body really know the difference?

 

[medicswag]

You can use regular epi 1:1000 in a neb to treat croup, but it's not "racemic" unless it's a 1:1 mix of D and L chiral molecules.

"Regular" epi is the levorotatory isomer, and studies have shown it works just as well, but it's a higher dose. (5mg Epi in 2-5ml of NS)


Sent from my iPhone.

It should also be noted that D and L are in no way related to d and l. Capitalization makes a huge difference here!

d and l refer to the direction in which a chiral molecule rotates plain polarized light.

D and L designations are assigned by comparing a molecule to glcyeraldehyde, and ultimately relating information about the arrangement of the substituents around the chiral center with regards to Cahn-Ingold-Prelog. But they do not provide any information on the optical activity of the molecule

 

[systemet]

Starting premise is invalid. Both enantiomers are biologically active.

Rice PJ, Miller DD, Patil PN. Epinephrine enantiomers: affinity, efficacy and potency relationships in rat smooth muscle tissues. J Pmcol Expt Ther (1989) 249(1): 242-248





TABLE2 90
Receptor properties in rat tissues 80
EffICaCy is the reciprocal of fractional occupancy at ı Efficac? is expressed
as (pECı - plc). pECı. pK,, and efficacy values for rat aorta from Rice et a!. 70
(1987).

(-ıEınephıne (+).Epineph#{241}ne Ratio 60
Aorta
pECse 9.19±0.06 7.52±0.06 49±6
plc 7.69±0.10 6.10±0.10 55± 16
Efficacya 42±9 38±14 1.4±0.3
Efficacyb 1.50±0.12 1.42±0.12 1.1 ±0.2
Portal vein
pECse 7.40 ± 0.06 5.94 ± 0.10 40 ± 10
plc, 6.41 ± 0.12 5.30 ± 0.20 18 ± 7
Efficacy 12±3 10±4 2.4±0.7
Efficacyı 0.99 ± 0.13 0.64 ± 0.21 1.5 ± 0.5

Spleen
pECse 6.99±0.07 5.45±0.04 39±6
PKd 6.18±0.12 4.96±0.19 26±9
Efficacy 10±2 6±1 1.8±0.5
Efficac? 0.81 ± 0.14 0.49 ± 0.19 1.7 ± 0.2

Vas deferens
pECse 7.35 ± 0.04 5.83 ± 0.05 34 ± 2
plc, 6.15 ± 0.10 4.66 ± 0.10 23 ± 6
Efficacyı 23±6 19±4 1.7±0.3
Efficac? 1.20 ± 0.11 1.17 ± 0.11 1.0 ± 0.2

 

[medicswag]

Starting premise is invalid. Both enantiomers are biologically active.

Rice PJ, Miller DD, Patil PN. Epinephrine enantiomers: affinity, efficacy and potency relationships in rat smooth muscle tissues. J Pmcol Expt Ther (1989) 249(1): 242-248





TABLE2 90
Receptor properties in rat tissues 80
EffICaCy is the reciprocal of fractional occupancy at ı Efficac? is expressed
as (pECı - plc). pECı. pK,, and efficacy values for rat aorta from Rice et a!. 70
(1987).

(-ıEınephıne (+).Epineph#{241}ne Ratio 60
Aorta
pECse 9.19±0.06 7.52±0.06 49±6
plc 7.69±0.10 6.10±0.10 55± 16
Efficacya 42±9 38±14 1.4±0.3
Efficacyb 1.50±0.12 1.42±0.12 1.1 ±0.2
Portal vein
pECse 7.40 ± 0.06 5.94 ± 0.10 40 ± 10
plc, 6.41 ± 0.12 5.30 ± 0.20 18 ± 7
Efficacy 12±3 10±4 2.4±0.7
Efficacyı 0.99 ± 0.13 0.64 ± 0.21 1.5 ± 0.5

Spleen
pECse 6.99±0.07 5.45±0.04 39±6
PKd 6.18±0.12 4.96±0.19 26±9
Efficacy 10±2 6±1 1.8±0.5
Efficac? 0.81 ± 0.14 0.49 ± 0.19 1.7 ± 0.2

Vas deferens
pECse 7.35 ± 0.04 5.83 ± 0.05 34 ± 2
plc, 6.15 ± 0.10 4.66 ± 0.10 23 ± 6
Efficacyı 23±6 19±4 1.7±0.3
Efficac? 1.20 ± 0.11 1.17 ± 0.11 1.0 ± 0.2

well now your just being silly. Do you understand what this data represents? These two molecules differ in their arrangment in 3D space, ofcourse they can not bind to the same receptor site!

 

[NomadicMedic]

I'm curious... if you have a clue about O-Chem, why did you post about racemic Epi in the first place?

 

[Shishkabob]

Too many numbers. My brain has just shut down.

 

[MSDeltaFlt]

Hey Guys,

Could racemic epinephrine be "macgyvered" by mixing epi and NS in the appropriate amounts?


Thanks,
Rob

Although Racemic Epinephrine does quite well in the treatment of Laryngotracheal Bronchitis, you must also be aware of something. With the concentration being 1:1 (thousand times stronger than 1:1000), there will also be a risk of rebound constriction and edema because it is so strong which is why most physicians stick with multiple albuterol nebs and uses Racemic Epi only when they have to.

 

[medicswag]

I'm curious... if you have a clue about O-Chem, why did you post about racemic Epi in the first place?

Because I love chemistry, but was not sure about the possibility of replacing one enantiomer with NS.