Amphotericin B versus azoles

[Mass Effect]

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First Aid made some corrections, but that just confused me. Which one of these cross the BBB? Or do they both?

 

[HelpPleaseMD]

Only one of the azoles cross the BBB. Not sure about Amphotericin B though. I think it has to be administered intrathecally for CNS action.

 

[Phloston]

HelpPleaseMD is right that amphotericin B must be given intrathecally because it does not cross the BBB.

I'm not sure about -azoles, but I think they don't cross the BBB either.

 

[HelpPleaseMD]

im pretty sure fluconazole penetrates the BBB. otherwise they couldnt be used to treat cryptococcal menigitis.

 

[Phloston]

im pretty sure fluconazole penetrates the BBB. otherwise they couldnt be used to treat cryptococcal menigitis.

I'm pretty sure ketoconazole at least doesn't.

I've just checked FA, and it does say that fluconazole can cross the BBB. Good call.

Thanks for the reinforcement, HelpPleaseMD 🙂

 

[HelpPleaseMD]

Phloston, I took a NBME test today where your question about acute renal ischemia came up. The answer is the proximal convuluted tubule

 

[MrBeauregard]

Fluconazole definitely crosses the BBB.

 

[Phloston]

Phloston, I took a NBME test today where your question about acute renal ischemia came up. The answer is the proximal convuluted tubule

Nice.

Yeah, I've come to figure that acute, severe ischaemia is cortex-damaging (e.g. diffuse cortical necrosis), whereas longer-term, sub-acute ischaemia hits the medulla (e.g. chronic analgesic nephropathy).

I'm scared to take an NBME btw. Because I'm not sitting the Step until December 21st, I figure I'll sit my first one in October or so, although I had originally thought I might sit one next month.

 

[HelpPleaseMD]

You could take one of the less important ones to gauge yourself. They are going to phase some of them out by the end of next month anyway so might as well take it before its gone. I doubt you will have any trouble though

 

[Mass Effect]

I'm pretty sure ketoconazole at least doesn't.

I've just checked FA, and it does say that fluconazole can cross the BBB. Good call.

Thanks for the reinforcement, HelpPleaseMD 🙂

The part that's confusing to me is that First Aid's correction page says this:

Amphotericin B
In the entry for Clinical use, in the third sentence, delete the phrase does not cross
blood-brain barrier. And to clarify, amphotericin B is first-line treatment of cryptococcal
meningitis.
​

So if it can't cross the BBB, why would they "correct" it?

Here's what it says for Azoles:

214 *
Azoles
In the entry for Clinical use, in the second sentence, delete the parenthetical phrase
(because it can cross blood-brain barrier).

Again, why correct it if some azoles can cross the BBB? Is it just to be more specific or something?

 

[HelpPleaseMD]

First aid is known to make terrible mistakes. They couldn't even get the clindamycin mechanism down right.

 

[Phloston]

Interesting.

I know for a fact that amphotericin B does not cross the BBB and must be given intra-thecally.

Btw, if you type "fluconazole blood brain barrier" into Google, look at the first result, even without clicking into it.

 

[Mass Effect]

I trust you. I just found it odd that FA felt the need to correct something that didn't really need to be corrected.

Thanks for your help guys!

 

[youngstown27]

The ability of antifungals to cross the blood-brain barrier is largely a function of their molecular weight, lipophilicity, and % binding to serum protein (which effectively increases MW). A MW of 300-400 daltons is considered to be a reasonable cutoff. Amphotericin B has a MW of 924, and also has > 95% binding to plasma protein, effectively limiting its ability to cross the b-b barrier. Alternatively, fluconazole has a MW of 309 with only 10% protein binding. In animal studies involving rabbits, the concentration of ampB found in the CSF is only 3% of serum concentration, whereas fluconazole is 74%. Therefore ampB is generally introduced intrathecally for CSF infection with pathogens such as cryptococcus.

 

[Krubes1226]

Fluconazole and voriconazole (for aspergillis meningitis) can cross the BBB. Does anyone know what they are using for the fungal meningitis outbreak? I'm assuming voriconazole but they said on the news (an MD) that they are being conservative with treatment due to the side effects of the treatment on the liver and kidney... That said- are they also using amphotericin B IV?

 

[Charles_Carmichael]

Fluconazole and voriconazole (for aspergillis meningitis) can cross the BBB. Does anyone know what they are using for the fungal meningitis outbreak? I'm assuming voriconazole but they said on the news (an MD) that they are being conservative with treatment due to the side effects of the treatment on the liver and kidney... That said- are they also using amphotericin B IV?

AmpB does not cross the blood-brain-barrier. It needs to be given intrathecally. So they wouldn't be giving IV AmpB for the fungal meningitis.