Cytochrome P450

The report also covers how you make and clear estrogen, testosterone, and thyroid hormone.

The CYP family are important there.

And then there's SHBG, which governs how much of your hormone is actually bioavailable.

And then ESR2, the estrogen receptor, the deiodinase genes.

The eighth area that we look at is detoxification.

And that's the one that changed my life the most.

So phase one and phase two liver detox, the CYP450 enzymes, CYP1A1, 1A2, 2E1, CYP3A4 and the rest.

The GST family that I mentioned, GSTM1 and the P1 and then there's NAT2 and PON1 and the vitamin D pathway genes.

As well as the analgesic duration tends to be shorter than the actual half-life of the drug and how long it hangs around in the body there.

There are some potential CYP enzyme interactions and stuff, so always good to double-check, look that up.

I'm not going to go into a ton of detail here on that.

But then I also wanted to mention...

Again, high affinity for that mu opioid receptor, so it's going to prevent other things from binding or kick things off potentially.

It can stay there for a long time as well.

It is hepatically metabolized, and it does have some CYP3A4 involvement there, so pay attention to that as far as drug interactions go.

And then adverse effect profile, you're going to have all the same things that can happen with other opioids.

Those who meet the criteria for surgery, like having a creatinine clearance less than 60 ml per minute or a serum calcium 1.0 milligrams per deciliter above the upper limit of normal, but simply cannot reach the operating room.

We start at 30 mg twice daily with food, we titrate slowly, we vigilantly police the CYP450 drug interactions, especially keeping an eye out for prodrugs like tramadol, and we relentlessly monitor serum calcium to prevent hypocalcemia.

It requires meticulous, detail-oriented management, but when utilized correctly and safely, it provides profound biochemical control for a very vulnerable patient population.

Well said.

Why would I combine castor oil and DMSO at this dilution? So one of the keys

with castor oil is that we use castor oil in general also to help support the detoxification pathways of the liver, the CYP450 enzyme detoxification pathway there.

But also it helps with lymphatics.

So it helps with lymphatic flow.

So think about aldo-ketoreductases, carbonyl reductases, aldehyde dehydrogenases.

specific like ALDH1, think about NADPH quinone oxidoreductase, and then the cytochrome P450s, which we brought already, all these enzymes we've talked about already.

But think about the CYP such as CYP2A5, CYP2B6, those are specific isoforms of cytochrome P450 enzymes.

I want you to also understand the metabolites generated by phase one enzymes are further modified by phase two conjugation enzymes, which will then chemically attach endogenous hydrophilic molecules to phase one reaction products to typically increase their solubility and therefore promote their excretion to remove them from the activity that they were brought in to carry out.

So estrogen clears in two phases in the liver.

So phase one, it uses an enzyme called CYP450.

So these enzymes convert estrogen into an immediate metabolite.

And then phase two conjugates these metabolites via glucuronidation and methylation.

So your two and your four OH types of estrogen, we just pee those out and the 16 type goes into bile and then into our digestive system and we poo that out.

But that 16 type can be turned back on later.

Alcohol, is metabolized through the CYP450 enzyme, which sounds familiar, right? So when your liver is occupied, breaking apart the alcohol from that glass of wine you've just had, estrogen clearance is backed up.

So estrogen is arriving into the liver and saying, hey, I'm ready to be cleared.

And there's increasing data about the potential importance of doing that.

But regardless, even though tacrolimus itself is not significantly cleared by dialysis, there are also interesting data In the setting of uremia, so the accumulation of uremic toxins, there may be impairment in hepatic cytochromes and in intestinal cytochrome activity, knowing that tacrolimus is chiefly metabolized by cytochrome P450 3A4 within 3A5 is kind of an offshoot that a lot of centers are now doing pharmacogenetic testing of to see if you're a poor or intermediate or rapid metabolizer for 3A5.

But regardless, I think in terms of the need for data and the dialysis population for something like tacrolimus, since there's already so much therapeutic drug monitoring and rapid adjustment, in a way, the need for empiric dosing in that population feels a little bit less since we are already so proactively measuring and making adjustments.

And because Frequently, at least when you're thinking about the indication of kidney transplant, immunosuppression, there's a bit of a well, if this patient has made it to dialysis, unfortunately, it is likely that graft has failed.