Blood Pressure

[john87412]

About AISA-021 – Aisa Pharma, Inc.

More than 27 million Americans suffer from Raynaud’s and yet no drug is specifically approved for the treatment of Raynaud’s disease in the United States.

aisapharma.com

To be clear, it's not genuinely a "cure", since it doesn't permanently fix it, but it did eliminate all symptoms for me. BP wasn't ideal and have to take something for it anyway, so it worked out perfectly.

Affected a couple of toes on each foot for me. Started about 10 years ago.

After the first month at 10mg I noticed symptoms seemed much better, but I wasn't certain. By the end of the 2nd month it was obvious things were improved immensely. Only the slightest cold induced symptoms.

A month after I increased to 20mg it was over. No symptoms whatsoever.

Full disclosure, I'm also using daily low dose tadalafil, which Ciln is combined with in the Reynauds treatment trial.

Trials Underway for New Raynaud's Drug - Raynaud's Association

Exciting news for Frosties: A clinical study is underway for a new Raynaud’s drug that could be the first FDA-approved drug specifically for Raynaud’s.

www.raynauds.org

(besides the pumps, LD tadalafil a great longevity drug that lowers all cause mortality, and especially the risk of heart attack or stroke. It's even FDA approved for this purpose. Sides are minor, if any, minor nose congestion is most common, and resolve within a month for the vast majority).

Spy pic of dangerous investigational drug Cilnidipine, kept safely away from the public in a secure lab in Boston, MA.

View attachment 339708

Tadalafil disrupts sleep, sure you can use sildenafil during the day but after a few months your receptors desensitize anyway.

 

[Ghoul]

Tadalafil disrupts sleep, sure you can use sildenafil during the day but after a few months your receptors desensitize anyway.

That's news to me. I've been taking it every morning for years and never had an issue, except for some minor nasal congestion that went away and never returned after the first few weeks.

 

[john87412]

That's news to me. I've been taking it every morning for years and never had an issue, except for some minor nasal congestion that went away and never returned after the first few weeks.

My sleep goes to sh*t while its in my system, sildenafil worked better cuz of the hl but as you said the nasal congestion is quite annoying. Another thing is pde5 inhibitors increase ur hr which I didnt like.

 

[ItCantBe]

That's news to me. I've been taking it every morning for years and never had an issue, except for some minor nasal congestion that went away and never returned after the first few weeks.

I second this, never had any sleep issues but still have the occasional stuffy nose if taken earlier in the day.

 

[explodingHeart]

That's news to me. I've been taking it every morning for years and never had an issue, except for some minor nasal congestion that went away and never returned after the first few weeks.

I can tolerate every drug I've ever tried including all types of food. Even tren was mild. But cialsis/tada stuffs up my airways and basically chokes me in my sleep.

Not that I care to run tren at this old age, not that I could even get it anymore, but would Ciln alleviate side effects of tren as well? Sympathetic drive, etc.

 

[Ghoul]

I can tolerate every drug I've ever tried including all types of food. Even tren was mild. But cialsis/tada stuffs up my airways and basically chokes me in my sleep.

Not that I care to run tren at this old age, not that I could even get it anymore, but would Ciln alleviate side effects of tren as well? Sympathetic drive, etc.

Yes. N channel blockers blunt sympathetic drive, ie heart rate, bp, adrenaline release etc. Cilnidipine is the only non sedating n channel blocker. Described as "smooth", vs something like clonidine.

 

[dasistmane]

Had an absolute nightmare on amlodipine.

Huge amount of water retention in my feet and legs. The aching kept me awake most nights. Really messed up my training too. It did lower my BP though.

Best alternative CCB that won't give me these sides?

Already running telm 40 and nebivolol 2.5

 

[dasistmane]

I'm trying to get my hypertension under control, but I'm dealing with hyperkalemia which started years ago, before any BP meds were introduced, so they don't want me on any ARB's or ACE inhibitors, which really sucks. I'm currently on Nebivolol 10mg ED and Clonidine 0.1mg 2x/day. I just realized recently through my own research that Nebivolol also has the potential to cause/exasperate hyperkalemia, so I'm going to need to address this with my nephrologist. He tried me on Amlodipine, but I got insane, INTENSE low back and hip pain, to the point of being entirely bedridden and in agony for days. I've never experienced anything like it in my life. Has anyone experienced or even heard of this kind of a reaction to amlodipine? My hypertension is still well managed, and I need more options. My pre-existing hyperkalemia (along with chronically low sodium) is really limiting my options.

I didn't have it as bad as you I don't think but ye. Amlodipine absolutely messed me up. Thought I had arthritic joints or something seriously wrong with me the pain got that bad.

How long after coming off it were you back to 100%?

 

[Ghoul]

Had an absolute nightmare on amlodipine.

Huge amount of water retention in my feet and legs. The aching kept me awake most nights. Really messed up my training too. It did lower my BP though.

Best alternative CCB that won't give me these sides?

Already running telm 40 and nebivolol 2.5

This is the reason Cilnidipine exists. In fact, for "cost efficiency" purposes, patients in countries where Ciln is available are often given cheaper Amlodipine first, and once those sides occur, they're switched to Cilnidipine.

They'd be much better off skipping amlodipine and going right to Ciln, but medicine values savings as much as outcomes in most cases. Not that Ciln is expensive, it's just that Amlodipine is as cheap as a pharmaceutical could be.

Unfortunately, Amlodipine not only causes edema as a side effect, it damages blood vessels over the long term in a way that makes edema almost inevitable after enough time. Cilnidipine doesn't, and adds long term protective effects for the kidneys as well.

 

[AllGoodThings]

I didn't have it as bad as you I don't think but ye. Amlodipine absolutely messed me up. Thought I had arthritic joints or something seriously wrong with me the pain got that bad.

How long after coming off it were you back to 100%?

I wasn't convinced it was the Amlodipine right away, so I continued it for a few days and the pain became unbearable, the worst I've ever felt, for the last two days of taking it. I discontinued it, and the next day the pain was improved, but still bad enough that moving around the house was difficult and painful, but manageable compared to the previous day where a 25ft walk from the couch to the bathroom took a lot of pain, hyperventilating, and time (no exaggeration at least 5 minutes to get there, 5 minutes to get back). A gradual daily improvement continued, with most all pain gone by day 7 of discontinuation, and absolutely no pain at 10 days. It was such a surreal experience, having an innocuous looking pill cause such agony so quickly, it's still hard to wrap my head around.

 

[dasistmane]

This is the reason Cilnidipine exists. In fact, for "cost efficiency" purposes, patients in countries where Ciln is available are often given cheaper Amlodipine first, and once those sides occur, they're switched to Cilnidipine.

They'd be much better off skipping amlodipine and going right to Ciln, but medicine values savings as much as outcomes in most cases. Not that Ciln is expensive, it's just that Amlodipine is as cheap as a pharmaceutical could be.

Unfortunately, Amlodipine not only causes edema as a side effect, it damages blood vessels over the long term in a way that makes edema almost inevitable after enough time. Cilnidipine doesn't, and adds long term protective effects for the kidneys as well.

Do we know the mechanisms of action that cause the intense pain that myself and @AllGoodThings have spoken about?

I've had water retention from other drugs but nothing has ever caused this level of discomfort and drop in QOL.

 

[Ghoul]

Do we know the mechanisms of action that cause the intense pain that myself and @AllGoodThings have spoken about?

I've had water retention from other drugs but nothing has ever caused this level of discomfort and drop in QOL.

TLDR, if you have strong "sympathetic tone", your body releases excessive adrenaline from the ends of nerves in response to certain stimuli. Cold, emotional stress, *and drops in blood pressure*.

Amlodipine drops bp by blocking the calcium "L" channels in medium and small blood vessels, but not tiny and microscopic vessels.

In response to this drop in bp, everyone, but particularly those with strong "sympathetic tone" release adrenaline from the ends of nerves, which among other things cause those tiny vessels to contract in an attempt to raise blood pressure and reduce blood flow to prevent blood from excessively cooling in extremities, to conserve energy.

The "fight or flight response".

The problem is you now have high blood flow going into tiny constricted vessels, stretching them out until water leaks out of their walls. This local tissue water retention (aka edema) can put pressure on nerves, and you feel pain.

The degree to which this happens depends on individual biology; and reactions like yours are rare but not unknown.

Cilnidipine blocks N calcium channels (in addition to L like amlodipine), preventing the release of adrenaline (noradrenaline aka epinephrine to be specific) that occurs during the sympathetic response (again, to stress, cold, or blood pressure drops), so small vessels stay relaxed , wide open and don't stretch, which prevents water from leaking out.

Blocking N channels also prevents increases in heart rate, and tubules in the kidneys from contracting that also occur when the sympathetic "fight or flight" response kicks in.

The cool thing about this is that it's very targeted, only blunting excessive sympathetic response, without the sedation other methods cause (like beta blockers, which block adrenaline receptors, rather than blocking adrenaline release via N channels).

If you're a naturally "high strung" person, you'll notice your body doesn't respond the way you're used to when you get angry, ie muscles tensing, bp rising, but otherwise, you don't feel any different.

 

[Mastedon]

Anyone have thoughts on a supplement like Now Foods Blood Pressure Heath capsules? It's Grape Seed Extract 150mg and Hawthorne Extract blend 300mg. I started taking it about a month ago when my BP was higher and on elevated use of compounds. Right now just on Test 250 and with Telm40, HCTZ12.5 and Ciln5 I average 115/75 (I'd like to get to 110/70).

Should I just drop it? Drop it and save it for when increasing compounds?
I didn't see much convincing evidence of its effectiveness although it could also help with lipids.
I'm leaning towards drop it then up the Ciln then Telm as needed.
Any thoughts or insight are appreciated!

 

[Ghoul]

Anyone have thoughts on a supplement like Now Foods Blood Pressure Heath capsules? It's Grape Seed Extract 150mg and Hawthorne Extract blend 300mg. I started taking it about a month ago when my BP was higher and on elevated use of compounds. Right now just on Test 250 and with Telm40, HCTZ12.5 and Ciln5 I average 115/75 (I'd like to get to 110/70).

Should I just drop it? Drop it and save it for when increasing compounds?
I didn't see much convincing evidence of its effectiveness although it could also help with lipids.
I'm leaning towards drop it then up the Ciln then Telm as needed.
Any thoughts or insight are appreciated!

I don't know how long you've been on those meds, but keep in mind it takes 4 weeks to get the full effect. If it hasn't been long, there's more of a reduction coming.

I don't trust otc supplements for serious medical issues, and prefer regulated pharma.

If you ultimately need more bp control, I'd increase the Ciln before Telm. You can go up to 20mg. Both are safe but Telm can cause hyperkylemia, while Ciln doesn't, and is even more kidney protective at higher doses.

 

[Ghoul]

Anyone have thoughts on a supplement like Now Foods Blood Pressure Heath capsules? It's Grape Seed Extract 150mg and Hawthorne Extract blend 300mg. I started taking it about a month ago when my BP was higher and on elevated use of compounds. Right now just on Test 250 and with Telm40, HCTZ12.5 and Ciln5 I average 115/75 (I'd like to get to 110/70).

Should I just drop it? Drop it and save it for when increasing compounds?
I didn't see much convincing evidence of its effectiveness although it could also help with lipids.
I'm leaning towards drop it then up the Ciln then Telm as needed.
Any thoughts or insight are appreciated!

I don't know how long you've been on those meds, but keep in mind it takes 4 weeks to get the full effect. If it hasn't been long, there's more of a reduction coming.

I don't trust otc supplements for serious medical issues, and prefer regulated pharma.

If you ultimately need more bp control, I'd increase the Ciln before Telm. You can go up to 20mg. Both are safe but Telm can cause hyperkylemia, while Ciln doesn't, and is even more kidney protective at higher doses.

 

[Mastedon]

I don't know how long you've been on those meds, but keep in mind it takes 4 weeks to get the full effect. If it hasn't been long, there's more of a reduction coming.

I don't trust otc supplements for serious medical issues, and prefer regulated pharma.

If you ultimately need more bp control, I'd increase the Ciln before Telm. You can go up to 20mg. Both are safe but Telm can cause hyperkylemia, while Ciln doesn't, and is even more kidney protective at higher doses.

Perfect, thanks for the insight! It's only been just under three weeks on the Ciln so I'll drop the otc and see where I'm at in a couple more weeks. Then as needed I'll up the Ciln before Telm. Very helpful!!

 

[Ghoul]

Perfect, thanks for the insight! It's only been just under three weeks on the Ciln so I'll drop the otc and see where I'm at in a couple more weeks. Then as needed I'll up the Ciln before Telm. Very helpful!!

Ciln's reduction is also easier to fine tune, with just a little more reduction with each additional 5mg, vs going from 40 to 80 telm that can easily overshoot your target.

 

[Mastedon]

Ciln's reduction is also easier to fine tune, with just a little more reduction with each additional 5mg, vs going from 40 to 80 telm that can easily overshoot your target.

So if I eventually have room to decrease something it should be the Telm from 40 to 20 correct?
Once I'm at 5 weeks stabilized of my current Telm40, HCTZ12.5 and Ciln5 should I try Telm20, HCTZ12.5 and Ciln10?
Is there anything I should do to counteract any issues with Telm (hyperkalemia or ?)?
Really appreciate the insight!

 

[Ghoul]

So if I eventually have room to decrease something it should be the Telm from 40 to 20 correct?
Once I'm at 5 weeks stabilized of my current Telm40, HCTZ12.5 and Ciln5 should I try Telm20, HCTZ12.5 and Ciln10?
Is there anything I should do to counteract any issues with Telm (hyperkalemia or ?)?
Really appreciate the insight!

Do you have any comorbidities like kidney or heart problems?

What got you on hctz?

 

[explodingHeart]

TLDR, if you have strong "sympathetic tone", your body releases excessive adrenaline from the ends of nerves in response to certain stimuli. Cold, emotional stress, *and drops in blood pressure*.

Amlodipine drops bp by blocking the calcium "L" channels in medium and small blood vessels, but not tiny and microscopic vessels.

In response to this drop in bp, everyone, but particularly those with strong "sympathetic tone" release adrenaline from the ends of nerves, which among other things cause those tiny vessels to contract in an attempt to raise blood pressure and reduce blood flow to prevent blood from excessively cooling in extremities, to conserve energy.

The "fight or flight response".

The problem is you now have high blood flow going into tiny constricted vessels, stretching them out until water leaks out of their walls. This local tissue water retention (aka edema) can put pressure on nerves, and you feel pain.

The degree to which this happens depends on individual biology; and reactions like yours are rare but not unknown.

Cilnidipine blocks N calcium channels (in addition to L like amlodipine), preventing the release of adrenaline (noradrenaline aka epinephrine to be specific) that occurs during the sympathetic response (again, to stress, cold, or blood pressure drops), so small vessels stay relaxed , wide open and don't stretch, which prevents water from leaking out.

Blocking N channels also prevents increases in heart rate, and tubules in the kidneys from contracting that also occur when the sympathetic "fight or flight" response kicks in.

The cool thing about this is that it's very targeted, only blunting excessive sympathetic response, without the sedation other methods cause (like beta blockers, which block adrenaline receptors, rather than blocking adrenaline release via N channels).

If you're a naturally "high strung" person, you'll notice your body doesn't respond the way you're used to when you get angry, ie muscles tensing, bp rising, but otherwise, you don't feel any different.

Theoretically, if I took amlo then slammed some ephedrine, it would cause massive edema and fuck me up?