Blood Pressure

[RandallFlagg]

He mentioned this before so I just looked it up. Likely to be approved off-label for systemic sclerosis.

“In September 2024, the U.S. Food & Drug Administration (FDA) granted orphan drug designation to AISA-021 (cilnidipine), a fourth-generation calcium channel antagonist with an increased selectivity for the N-type calcium channel.1 This designation is for the agent’s development as a treatment for systemic sclerosis (SSc).”

Yeah...but is anyone appearing to pick the med up in the USA? I realize I could do some more digging..but yeah I recall him saying this and it was the only way the drug was gonna be approved at all in the USA.

Mostly trying to get a sense of whether this will be enough for 'normies" to get a access to it.

 

[verylargeshoes]

Yeah...but is anyone appearing to pick the med up in the USA? I realize I could do some more digging..but yeah I recall him saying this and it was the only way the drug was gonna be approved at all in the USA.

Mostly trying to get a sense of whether this will be enough for 'normies" to get a access to it.

That I don't know, but the orphan drug designation grants a period of exclusive market rights for the company bringing the drug to market. So even if doctors can prescribe it off-label, don't expect cheap generics of it, and don't expect your insurance company to approve it.

 

[Photon]

Yeah...but is anyone appearing to pick the med up in the USA? I realize I could do some more digging..but yeah I recall him saying this and it was the only way the drug was gonna be approved at all in the USA.

Yup.
No-one is going to spend all that money and time on clinical trials if they can't earn from it. It will be charged at high prices to people with systemic sclerosis. As far as insurance companies are concerned, it is not a hypertension drug, it is meant for systemic sclerosis if it gets approved.

With orphan designation, they have exclusivity for 7 years unless challenged, which allows them to maximize profits over that 7 year period.

 

[Ghoul]

I know you don't have a crystal ball (or maybe you fucking do...lol)

But what would you put the odds at that Cilnidipine will be available in the USA in the next 3-5 years (which Im guessing the only hope of that happening being if the Tadalafil-Cilnidipine protocol ends up being a success?)

I'm planning to stock up on a few years worth...and who knows what the world will look like by 2030...but just wondering if there is any rationale reason to hope for a US version (of course off label for BP so that may just be another impossible regulatory hurdle).

He mentioned this before so I just looked it up. Likely to be approved off-label for systemic sclerosis.

“In September 2024, the U.S. Food & Drug Administration (FDA) granted orphan drug designation to AISA-021 (cilnidipine), a fourth-generation calcium channel antagonist with an increased selectivity for the N-type calcium channel.1 This designation is for the agent’s development as a treatment for systemic sclerosis (SSc).”

The problem is what it's going to be approved for.

For Raynaud's symptoms (one of many symptoms of SSC).

That will be the only approved use,

AISA isn't interested in selling a cheap blood pressure drug.

They're selling an "orphan" drug for a rare disease with no other treatment.

As the only drug available to treat this rare condition, they're going to price it accordingly (for the insurance plans that will be paying for it).

Other "repurposed" oral drugs like this, for very small numbers of patients, cost between $30,000-$100,000 year.

Sound crazy?

Thalomid. Around since the 1950s. 2¢ a pill in India, Brazil, etc.

Repurposed by Celgene to treat leprosy side effects, and approved with orphan status by the FDA like Cilnidipine.

Price increased to $150 tablet / $80,000 a year for treatment.

There are dozens of examples like this.

The cheapest example I could find is $6,000 a year.

Until the Cilnidipine orphan drug patent runs out 20 years from now, it won't be a cheap generic that will be priced low enough for blood pressure use (which will be "off label" use).

It's cheap enough and important enough to me (I have Raynauds, Ciln got rid of the symptoms), that I bought ~8 years worth. 1400 20/40 combo with Telm, and 1200 20mg Cilniheal (in case I need to use it without Telm for any reason).

I'll top it off with fresh supply once in a while so long as it remains available.

In blister packs, it's protected from light, air, moisture, and in a fridge at 36f, given its stability data, it's near certain it'll remain potent for 8 years or more.

If you're considering quantities like this, it's worth asking for a quote. You should expect a rock bottom price for 100+ strips of anything. You can DM me and I'll tell you what I know if you need help getting a deal.

 

[explodingHeart]

I'll make it short and sweet.

I was on Amlodipine for a decade and it didn't help AT ALL.

Cilnidipine made all the difference in the world. At this point the thought of losing access to it gives me a little anxiety tbh.

You know how much those "minor" symptoms can really bring down your quality of life.

Sorry for my dumb questions, but would you feel Clin makes it safe to use HGH?

Only gear alone I can even skate by no BP med (I still take Telmi). HGH blows up my BP/HR.

On top of that, chatGPT, etc. tells me GH increases pressure inside the kidney, so even if your BP is good, you're still doing damage. It says using Cilnidipine makes it much safer to use GH.

No idea how true any of this is. But I'd like to do a blast with 10+ iu GH and 1G of test safely as possible.

 

[Ghoul]

Sorry for my dumb questions, but would you feel Clin makes it safe to use HGH?

Only gear alone I can even skate by no BP med (I still take Telmi). HGH blows up my BP/HR.

On top of that, chatGPT, etc. tells me GH increases pressure inside the kidney, so even if your BP is good, you're still doing damage. It says using Cilnidipine makes it much safer to use GH.

No idea how true any of this is. But I'd like to do a blast with 10+ iu GH and 1G of test safely as possible.

It's mechanistically true that Ciln should make rHGH use safer for the kidneys.

Put simply, rHGH raises internal kidney pressure, Ciln lowers it.

There haven't been any studies using rHGH, but Ciln has been proven to protect kidneys and slow the progression of kidney disease by lowering pressure, and there's no reason to expect it won't provide similar protection during rHGH use (or just plain hypertension).

In studies, even with the same reduction in blood pressure, Ciln protected kidneys more than other BP meds, indicating it has a unique kidney protective effect.

By the way, I'd normally be skeptical of a new drug with "all upside", but it's been around for 30 years in Japan. That's a lot of "patient years" of safety data. It's only new for us.

 

[Nidus]

If I could, I'd be in one of the trials. The meds are straightforward, very effective, no danger signals, and there's already strong evidence risks drop significantly by lowering Lp(a).

It seems Lp(a) puts smaller vessels that get less attention at greatest risk. IE, in your legs. More a concern for quality of life than outright death, but still.

What a time to be alive. We have the tools and solid evidence we need to avoid the worst outcomes those not too long ago were helpless against. The extinction of heart disease is in sight.

This is the news service I use to stay on top of developments in medicine, consider signing up (for free, I think you might have to pretend you're a healthcare provider).

High Lp(a) Signals Risk Beyond The Coronaries

High levels of Lp(a) may predict incidence and progression of extracoronary athero-sclerotic vascular disease — a combination of peripheral artery disease and carotid artery stenosis, study finds.

www.medscape.com

Pretty interesting, i just have bookmarks of scientists or doctors i follow on their social media and publication page and check it all once weekly for an update or so (tracking absolutely everything or nearly everything about blood sugar and mito stuff here)

 

[explodingHeart]

It's mechanistically true that Ciln should make rHGH use safer for the kidneys.

Put simply, rHGH raises internal kidney pressure, Ciln lowers it.

There haven't been any studies using rHGH, but Ciln has been proven to protect kidneys and slow the progression of kidney disease by lowering pressure, and there's no reason to expect it won't provide similar protection during rHGH use (or just plain hypertension).

In studies, even with the same reduction in blood pressure, Ciln protected kidneys more than other BP meds, indicating it has a unique kidney protective effect.

By the way, I'd normally be skeptical of a new drug with "all upside", but it's been around for 30 years in Japan. That's a lot of "patient years" of safety data. It's only new for us.

I realize this is stupid, but if I was gonna do a serious long blast, add serious mass and since it's fairly cheap from india.

What about: telmi / ciln and a SGTL2 inhibitor?

For max kidney protection.

 

[Ghoul]

With modern meds that have few "off target" effects, I think the old general rule of "the less pharmaceutical intervention the better" doesn't always apply, and for the best possible outcomes a more nuanced approach is needed.

Preventative medicine has been framing risks like high blood pressure. lipids. and by extension end organ damage in terms of "exposure time" similar to cigarette smoking. "Pack years" of LDL over 60, for instance.

The greatest predictor of future health issues is the cumulative amount of harmful exposure.

So any time you can reduce the amount of exposure to a given risk, in this case to your kidneys, it's worth doing (weighed against any new risks being introduced by whatever med you're using).

I haven't looked deeply into SGLT2's, other than hearing them regularly spoken about as part of a "secondary prevention" stack doctors prescribe, ie, being used after something terrible has already happened like heart failure. I get the impression they're relatively benign in terms of risks, similar to GLPs as protective compounds, and are good for kidney protection among other things. like just dumping excess glucose out of your system.

If I knew I was about to put my kidneys through hell, I would definitely use every tool in my toolbox to prevent damage, since fully "bouncing back" isn't something you can count on with organs. It's more like "using up".

I think @BamaCrazy knows a lot about SGLT2s and is using them. Maybe he can speak to side effects and if anything needs to be monitored.

 

[john87412]

It's mechanistically true that Ciln should make rHGH use safer for the kidneys.

Put simply, rHGH raises internal kidney pressure, Ciln lowers it.

There haven't been any studies using rHGH, but Ciln has been proven to protect kidneys and slow the progression of kidney disease by lowering pressure, and there's no reason to expect it won't provide similar protection during rHGH use (or just plain hypertension).

In studies, even with the same reduction in blood pressure, Ciln protected kidneys more than other BP meds, indicating it has a unique kidney protective effect.

By the way, I'd normally be skeptical of a new drug with "all upside", but it's been around for 30 years in Japan. That's a lot of "patient years" of safety data. It's only new for us.

Can Ciln cause chest tightness or anxiety ? Getting off Amlo was a nightmare that I dont want to experience ever again.

 

[BamaCrazy]

Can Ciln cause chest tightness or anxiety ? Getting off Amlo was a nightmare that I dont want to experience ever again.

Cilnidipine doesn’t cause me any sides at all. Amlodipine gave me bad edema so I switched.

Here is a case study where Cilnidipine lowered BP caused by psychological stress.

Cilnidipine lowered psychological stress-induced increase in blood pressure in a hypertensive man: a case report - PMC

In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood ...

pmc.ncbi.nlm.nih.gov

 

[Ghoul]

Can Ciln cause chest tightness or anxiety ? Getting off Amlo was a nightmare that I dont want to experience ever again.

No it doesn't do that.

I would call Ciln an "atypical anti-anxiety" med.

Where most anti-anxiety meds slow people down or cause sedation. Ciln isn't noticeable until some anxiety inducing situation starts to happen. Then it blunts the physical repose (caused by adrenaline, which Ciln reduces the release of). This lack of physical effects from stress, like muscle tension and blood pressure rise, prevents the feedback that would normally occur back to your brain increasing stress levels further. Ciln breaks this feedback cycle.

You notice this "anti-anxiety" effect by what doesn't happen, not by anything it does.. There's no brain fog. Thoughts are still clear. You're still aware of the presence of the stressful stimulus, but because your body doesn't respond with "physical panic", ie preparing for fight or flight, the mind seems to be reassured by the calm state of your body, and stress doesn't spiral upwards the way the mind initiated stress -> physical feedback loop would normally happen in "High adrenal tone individuals".

I'll just add I got a hint of this effect at 10mg. But it was much more significant about a month after titrating to 20mg.

Really an ideal BP med for anyone who's "high strung" to any degree. The Japanese seem to be aware of this property of Ciln more than the clinical documentation suggests, making it a first choice for doctors treating high BP in businessmen under pressure, for instance. This type of hypertension benefits most from Ciln, vs the types that come from other causes like excess sodium.

 

[explodingHeart]

No it doesn't do that.

I would call Ciln an "atypical anti-anxiety" med.

Where most anti-anxiety meds slow people down or cause sedation. Ciln isn't noticeable until some anxiety inducing situation starts to happen. Then it blunts the physical repose (caused by adrenaline, which Ciln reduces the release of). This lack of physical effects from stress, like muscle tension and blood pressure rise, prevents the feedback that would normally occur back to your brain increasing stress levels further. Ciln breaks this feedback cycle.

You notice this "anti-anxiety" effect by what doesn't happen, not by anything it does.. There's no brain fog. Thoughts are still clear. You're still aware of the presence of the stressful stimulus, but because your body doesn't respond with "physical panic", ie preparing for fight or flight, the mind seems to be reassured by the calm state of your body, and stress doesn't spiral upwards the way the mind initiated stress -> physical feedback loop would normally happen in "High adrenal tone individuals".

I'll just add I got a hint of this effect at 10mg. But it was much more significant about a month after titrating to 20mg.

Really an ideal BP med for anyone who's "high strung" to any degree. The Japanese seem to be aware of this property of Ciln more than the clinical documentation suggests, making it a first choice for doctors treating high BP in businessmen under pressure, for instance. This type of hypertension benefits most from Ciln, vs the types that come from other causes like excess sodium.

AI tells me Clin's N type calcium channel blocking maxes out at 10mg. So if your BP is fine, there's nothing to gain to moving to 20mg if you're looking to

- Get more of a calming effect
- Nullify the harsh effects of HGH, etc. (my use case)
- Or nullify diet drugs (ephedrine, etc.)

Is it true? I noticed you were using 20mg? What gain did you get over 10mg?

 

[Ghoul]

AI tells me Clin's N type calcium channel blocking maxes out at 10mg. So if your BP is fine, there's nothing to gain to moving to 20mg if you're looking to

- Get more of a calming effect
- Nullify the harsh effects of HGH, etc. (my use case)
- Or nullify diet drugs (ephedrine, etc.)

Is it true? I noticed you were using 20mg? What gain did you get over 10mg?

AI is wrong. Dose is 5, 10, or 20mg.

I have both individual and combo (with Telm 40mg) at Ciln 20mg.



Going from 10 to 20:

- Reduced BP by about 5 systolic and 3 diastolic.

- Lowered RHR by 3.

-The blunting of "physical response to psychological stress" became much more pronounced, despite being a subtle effect. "Subtle" because of what *doesn't* happen in response to stress (bp rise, muscle tension) that normally would.

-Sleep improved.

 

[explodingHeart]

AI is wrong. Dose is 5, 10, or 20mg.

I have both individual and combo (with Telm 40mg) at Ciln 20mg.

View attachment 341273View attachment 341274

Going from 10 to 20:

- Reduced BP by about 5 systolic and 3 diastolic.

- Lowered RHR by 3.

-The blunting of "physical response to psychological stress" became much more pronounced, despite being a subtle effect. "Subtle" because of what *doesn't* happen in response to stress (bp rise, muscle tension) that normally would.

-Sleep improved.

Thanks! I'm using this solely to offset the negatives of HGH. Injecting GH for me is like injecting liquid meth. 10mg didn't do the job. I'll work up to 20.

 

[Ghoul]

Thanks! I'm using this solely to offset the negatives of HGH. Injecting GH for me is like injecting liquid meth. 10mg didn't do the job. I'll work up to 20.

I was surprised at how much more pronounced the "N channel", ie, sympathetic nervous system Adrenaline release blocking, impact of 20mg was vs 10mg. If using. combination ARB/CCB, this might be the only situation where lowering the ARB dose to "make room" for a higher dose of the CCB is preferable*

*. (unless you need more BP reduction anyway, then just leave the ARB alone and titrate up Ciln, I didn't want to lower BP any further so dropped Telm from 80 to 40 to up Ciln to 20).

** Keep in mind it takes 2 weeks after starting a CCB or changing dose to make significant impact, and 4 weeks for full effect, so be patient.

 

[explodingHeart]

I was surprised at how much more pronounced the "N channel", ie, sympathetic nervous system Adrenaline release blocking, impact of 20mg was vs 10mg. If using. combination ARB/CCB, this might be the only situation where lowering the ARB dose to "make room" for a higher dose of the CCB is preferable*

*. (unless you need more BP reduction anyway, then just leave the ARB alone and titrate up Ciln, I didn't want to lower BP any further so dropped Telm from 80 to 40 to up Ciln to 20).

** Keep in mind it takes 2 weeks after starting a CCB or changing dose to make significant impact, and 4 weeks for full effect, so be patient.

Yes, exactly. My BP will get fairly low at the end of the day after the liquid adrenaline injection of GH starts to wear off.

I was going to do telmi 40 or even 20 and 20mg Ciln.

It's weird how 500 to 1g of test has no effect on BP, but even tiny amounts of GH make me feel amped up more than taking ephedrine.

 

[Ghoul]

Yes, exactly. My BP will get fairly low at the end of the day after the liquid adrenaline injection of GH starts to wear off.

I was going to do telmi 40 or even 20 and 20mg Ciln.

It's weird how 500 to 1g of test has no effect on BP, but even tiny amounts of GH make me feel amped up more than taking ephedrine.

rHGH can boost sympathetic drive a few different ways; but the short term nature of yours makes me suspect it's the GH induced FFA release (others rely on IGF, and that's fairly stable, not quickly up and down).

TLDR, some people are very sensitive to an increase in FFA, which can act as a "stress signal", Free fatty acids cross the blood brain barrier, triggering CNS adrenaline release, hits the vagal nerve upping cardiac output (like Reta does for some), and since FFAs are a modulator of adregenic receptor sensitivity, amplify the effect of the already increased levels of adrenaline being release. And all these things feed back on each other in a "stress loop".

Ciln won't stop it all, but it'll blunt it, break the feedback loop, and without causing sedation that other drugs would, since it's only lowering the additional release triggered by sympathetic nervous system stress rising, not blunting the "normal" level of adrenaline you need to function normally.

For context, one of the most potent anti-pain induced stress treatments is an N channel blocker injected into the spinal fluid, Ziconotide (a snail toxin), given in hospitals to stop the adrenaline responses to severe trauma. Ciln is a much weaker, but same mechanism of action compound.

 

[Sera]

Thanks! I'm using this solely to offset the negatives of HGH. Injecting GH for me is like injecting liquid meth. 10mg didn't do the job. I'll work up to 20.

What dose do you take brother?

I just had a big adrenaline dump that I attributed to TNE but it’s also true that I increased the GH dose last night by a little. Not sure if that could have impacted it. Only increased by 0.2iu so probably not.

Had me feeling like I was hooked up to an adrenaline drip. Heart rate 160 or something for a period. My SSRI I just started helped me just ride it out though without having a panic attack or anything which was nice

Just took a propranolol to give my body a rest after that.

 

[verylargeshoes]

Ziconotide (a snail toxin), given in hospitals to stop the adrenaline responses to severe trauma.

That’s some peak Ghoul right there