#13

I’m not really familiar with these drugs, so checked on Wikipedia:

One thing caught my attention… probably a low risk, but definitely something I’d want to avoid “Severe side effects may include priapism”

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#14

Sources I found say it is “very rare”. A 2020 paper mentions 18 cases reported: Priapism – A rare side effect of alpha blockers: Report of 2 cases and literature review | Revista Internacional de Andrología

Alpha 1 blockers have been used for more than 30 years and they’re in the top 200 most prescribed drugs in the US. So if that’s 18 cases in history that’s very very very low. But good to know for someone with a personal or family history of priapism.

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#15

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp2.934

This paper found 122 cases with tamsulosin:

In several patients, priapism resolved following discontinuation of tamsulosin and recurred after its reintroduction. Both in the published and unpublished data, for majority of the cases, the time to onset of priapism was within few days following the first intake of tamsulosin.
So far, there are no studies that explored the dose–response relationship of tamsulosin and priapism. Besides, in all of the cases including both the retrieved and published ones, where dose of tamsulosin was reported, there was no issues of overdose except in one case. Thus, more information is required to conclude on this criterion.

Tamsulosin is more selective so it’s supposed to have fewer side effects and it’s way more commonly used (top 24 drug in the US, considering that it’s almost only used by men it’s huge): The Top 300 of 2021

So maybe the risk is higher for terazosin / doxazosin. But it’s hard to find data.

#16

A potentially bigger risk than priapism: Cardiomyocyte Alpha-1A Adrenergic Receptors Mitigate Postinfarct Remodeling and Mortality by Constraining Necroptosis 2024

In our single-center clinical study, the use of α-blockers increased risk of mortality after MI, the first demonstration that these commonly used drugs may impact survival in high-risk patients.

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(However, this is survival post-MI: what about the risk of MI itself? And all-cause mortality?)

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#17

Effect of low‐dose terazosin on arterial stiffness improvement: A pilot study 2024

We enrolled patients aged over 40 with elevated arterial stiffness, defined as a brachial‐ankle pulse wave velocity (baPWV) ≥1400 cm/s, who were administered Terazosin (0.5 and 1.0 mg/day) from December 2020 to June 2023.
(1) Arterial stiffness significantly improved (at least a 5% reduction in baPWV) in 50.0% of patients at 3 months, 48.6% at 6 months, 59.3% at 9 months, and 54.4% at 12 months, respectively. (2) Those with higher baseline baPWV and hypertension exhibited a significantly reduced risk of non‐response. (3) Terazosin was associated with a reduction of baPWV at 1‐year follow‐up (linear regression: β = −165.16, p < 0.001). This pilot study offers valuable insights into the potential significance of Terazosin in improving arterial stiffness and paves the way for future randomised clinical trials in combating vascular ageing.
Terazosin, an α 1‐adrenergic receptor antagonist, has demonstrated efficacy in augmenting glycolysis by activating an initial ATP‐producing enzyme in the glycolytic pathway, thereby increasing intracellular ATP levels, and exhibiting potential therapeutic effects in diseases such as Parkinson. Increasing ATP could play a role in retarding cellular ageing, as well as enhancing the activity of endothelial nitric oxide synthase to facilitate the release of nitric oxide and vasodilation.
Considering the association between vascular stiffness and metabolic inflexibility, similar to the ageing process, we hypothesised that Terazosin may also have efficacy on anti‐vascular stiffness. Therefore, we conducted a pilot study to investigate the effect of low‐dose of Terazosin on the improvement of arterial stiffness.
To minimise adverse effects from blood pressure reduction, we employed low doses of Terazosin (0.5 mg or 1.0 mg/day) to investigate its blood pressure‐independent positive impact on vascular stiffness in middle‐aged and elderly human subjects.
We compared the Terazosin study with previous reports on antihypertensive drugs. Previous research has shown that elevated arterial stiffness can precede the onset of high blood pressure, highlighting the importance of intervening in vascular stiffness even in non‐hypertensive patients. Our findings revealed that Terazosin significantly improved vascular stiffness in both groups, with consistent trends observed in blood pressure changes and arterial compliance improvements attributed to the medication. No adverse effects from excessive blood pressure reduction were observed, indicating its safety and efficacy.
No heterogeneity was observed in the risk for vascular improvement non‐response with varying doses of Terazosin usage, suggesting that lower dose (0.5 mg/day) Terazosin treatment remains effective.

If confirmed by larger trials, good to know that even 0.5 mg/day can improve arterial stiffness @DrFraser:

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#18

Surprising clinical differences among alpha blockers demonstrated in post-marketing event rates

Overall, doxazosin had higher incidence of side effects than alfuzosin, which in turn had higher incidence than prazosin, tamsulosin, and terazosin; the latter three were not different from one another in rates of overall side effects. Alfuzosin was more likely to cause a fall than any other alpha blocker.

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#19

One more serious paper on the neuroprotective potential of alpha blockers: Tamsulosin use in benign prostatic hyperplasia and risks of Parkinson’s disease, Alzheimer’s disease and mortality: An observational cohort study of elderly Medicare enrollees 2024

The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68–0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91–0.97). For Parkinson’s disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66–0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72–0.88). For Alzheimer’s disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65–0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76–0.92). Tadalafil was associated with risk reduction (27–40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases.

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Tamsulosin seems to be a terrible drug that should be avoided at all cost. Among alpha blockers, terazosin seems best for neuroprotection and it’s also safer (paper above).

Tadalafil is interesting but I can imagine many biases. Also, the 1y use OR is not lower compared to any use, which suggests potential biases. For alpha blockers it is lower.

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Pill Splitting Ezetimibe and Bempedoic Acid to Save Money, Lower Side-effect risk
#20

Pinging tamsulosin users @desertshores and @jwpenuel FYI.

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#21

Shit. Thank you for this.

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#22

“Tamsulosin”
I am not promoting tamsulosin and I am always looking for the best meds to take.
Millions of men are taking tamsulosin.

“Estimate: If we conservatively estimate that tamsulosin is prescribed to about 20-30% of men with BPH, this would translate to approximately 120 million to 180 million men worldwide taking tamsulosin for BPH.”

I have been taking tamsulosin for 25+ years with no negative side effects that I am aware of.

Alfuzosin might be the better choice. Next time I visit my PCP I will ask him about changing.
(For those who don’t want or can’t get a prescription, it is still another cheap drug available from India.)

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#23

I wonder why that paper didn’t do any comparisons with silodosin?

Also, couldn’t the lower ORs of the other alpha blockers just mean that tamsulosin has no neuroprotective action while the others do, as opposed to tamsulosin actually having a negative effect.

There is a major advantage to the more selective alpha blockers like tamsulosin and silodosin. They’re much less likely to have an effect on blood pressure and cause dizziness/syncope, which can have very dangerous/deadly sequelae, especially for the elderly (broken hips, head injuries, etc).

#24

The issue with long-term neurotoxicity is that it’s hard (if not impossible) to detect in typical clinical trials on humans and on animal or cell models as 1/ they take years if not decades to develop and 2/ our models for these diseases aren’t great.

So it’s only with well done emulated trials / longitudinal studies that we can detect signals pointing to detrimental or protective effects. The data started being collected in the 2000s-2010s so it’s only now that we can measure the long-term effects. That’s why we’re starting to discover many unexpected effects of existing drugs (whether positive like for telmisartan or negative for tamsulosin).

So here we have more than 3 papers
by different research teams from different research institutions in various countries published in the world’s best journals all concluding that alternatives to tamsulosin should be preferred. Given that these alternatives are well studied and safe, that’s more than enough for me to conclude.

I’ll check. It might not be used often enough to detect signals.

You’re correct: dutasteride and finasteride had the same ORs for AD and PD as tamsulosin so it’s probably alpha blockers and tadalafil being neuroprotective than tamsulosin being neurotoxic. However all drugs had a lower all cause mortality than tamsulosin. That’s actually the most concerning finding.

This recent meta analysis suggests tamsulosin is NOT safer than terazosin: Terazosin / doxazosin / alfuzosin may protect against dementia with Lewy bodies - #18 by adssx

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#25

@Davin8r actually check the table: they looked at silodosin and it is as bad as tamsulosin.

#26

Another older paper found a +15% lifespan extension on worms with doxazosin: A pharmacological network for lifespan extension in Caenorhabditis elegans 2013

I’ll discuss with Ora Biomedical to reproduce these findings and also test alfuzosin as the study on humans found an even lower death rate among its users.

Doxazosin also identified as potentially neuroprotective in this other paper: Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles 2024

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#27

So terazosin seems the overall winner with fairly low risk of side effects yet max potential neuroprotection.

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#28

Terazosin or tadalafil. Although ideally we’d like research papers to look at a composite event such as “death or AD or PD”. Terazosin might seem better at neuroprotection than alfuzosin because alfuzosin patients don’t die, live longer and therefore are more likely to be diagnosed with PD or AD?

#29

I meant within the alpha-blocker meds. One could take both terazosin and tadalafil together, since they have different mechanisms of action, as long as blood pressure and side effects are manageable.

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#30

As they’re both approved for BPH, based on this paper alone why would one prefer terazosin to tadalafil? (just curious, based on mechanistic understanding, terazosin looks better to me)

#31

Based on a quick literature review, apparently tadalafil works just as well as alpha blockers for BPH and has the added benefit of improving sexual dysfunction. However, this was not my experience at all when I had BPH because tadalafil did absolutely nothing for my urinary symptoms while alpha blockers helped quite a bit (for a while, until symptoms got bad enough for surgical fix). This was also the “real world” experience of every urologist I saw over the years (alpha blockers>>tadalafil).

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#32

Interesting so the comparison of tadalafil to alpha blockers in the above paper might be misleading. If what you say is true then urologists would probably prescribe alpha blockers to patients with more advanced BPH and tadalafil to those with mild BPH and/or erectile dysfunction.

So one more point for terazosin…

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