Anyone have problems with Losartan?

[Hip]

It briefly mentions it in this article: Timeline of the Marshall Protocol Discoveries:

1999 – Marshall learns that other patients with sarcoidosis who were administered Angiotensin Receptor Blockers (ARBs) often developed a neurological reaction. Marshall starts a sabbatical in early 2001 in order to further investigate this reaction.

 

[Art Vandelay]

I am not even sure if this phenomenon occurs with all ARBs, or just with olmesartan. And I don't know which specific chronic diseases this phenomenon appears in; but it seems to be many, as people with various chronic diseases experience the immunopathology, if you read the MP forum.

It can happen with other ARBs. Olmesartan wasn't available in Australia when I first started on the MP, so they used candesartan instead. It has pretty much the same effect (although the Herxing isn't quite as rough on olmesartan I'd say).

 

[uglevod]

(although the Herxing isn't quite as rough on olmesartan I'd say).

Hopefully this means extra die off from VDR agonism.

Olmesartan wasn't available in Australia when I first started on the MP, so they used candesartan instead. It has pretty much the same effect (although the Herxing isn't quite as rough on olmesartan I'd say).

AT1 is expressed on many cells including macrophages; maybe suppressing AT1 on their surface has some additional beneficial effects(independent to the specific ARB used) by preventing viruses to enter, effectively making immune cells more active(less suppressed(including VDR suppression) by all intracellular viruses, not only COVID type ones):

__________
Corona 2020
Considerations by Dietrich Klinghardt MD, PhD
April 16, 2020
https://christineschaffner.s3.amazonaws.com/files/CoronaUS-Update-4-20.pdf

with an advice on ARB vs ACE on page 17:

ARBs (Angiotensin Rezeptor Blocker) vs. ACE Inhibitoren

The SARS-CoV-2 virus uses the angiotensin II receptor as an entry portal into the lung-cell (Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656. [Epub ahead of print] • Dimitrov, D. S. The secret life of ACE2 as a receptor for the SARS virus. Cell, 2003; 115(6), 652–653”)

Angiotensin Rezeptor Blockers (ARBs) make the doors difficult to pass through. Their generic name ends on “Tarsan” (losartan (Cozaar), candesartan (Atacand), telmisartan (Micardis), and Valsartan (Diovan), fimasartan (Kanarb).

ACE Inhibitors are often fatally mistaken for the above. They are a different class of chemicals and dangerous for the Covid Patient. They block the formation of angiotensin II. In response the alveoli express (=create) more ACE II receptors and the virus gains far easier access to invade. Don’t do it! Don’t allow it! ACE inhibitors are older and less expensive – many health plans have forced our patients to use them instead of the ARBs (Fang, Lei, George Karakiulakis, and Michael Roth. "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?." The Lancet Respiratory Medicine (2020). The “forbidden” drugs. Their generic name ends on “Pril”: captopril, lisinopril, benazepril, zofenopril, perindopril, trandolapril, enalapril and ramipril.
___________

 

[hopeforaday22]

Hopefully this means extra die off from VDR agonism.



AT1 is expressed on many cells including macrophages; maybe suppressing AT1 on their surface has some additional beneficial effects(independent to the specific ARB used) by preventing viruses to enter, effectively making immune cells more active(less suppressed(including VDR suppression) by all intracellular viruses, not only COVID type ones):

__________
Corona 2020
Considerations by Dietrich Klinghardt MD, PhD
April 16, 2020
https://christineschaffner.s3.amazonaws.com/files/CoronaUS-Update-4-20.pdf

with an advice on ARB vs ACE on page 17:

ARBs (Angiotensin Rezeptor Blocker) vs. ACE Inhibitoren

The SARS-CoV-2 virus uses the angiotensin II receptor as an entry portal into the lung-cell (Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656. [Epub ahead of print] • Dimitrov, D. S. The secret life of ACE2 as a receptor for the SARS virus. Cell, 2003; 115(6), 652–653”)

Angiotensin Rezeptor Blockers (ARBs) make the doors difficult to pass through. Their generic name ends on “Tarsan” (losartan (Cozaar), candesartan (Atacand), telmisartan (Micardis), and Valsartan (Diovan), fimasartan (Kanarb).

ACE Inhibitors are often fatally mistaken for the above. They are a different class of chemicals and dangerous for the Covid Patient. They block the formation of angiotensin II. In response the alveoli express (=create) more ACE II receptors and the virus gains far easier access to invade. Don’t do it! Don’t allow it! ACE inhibitors are older and less expensive – many health plans have forced our patients to use them instead of the ARBs (Fang, Lei, George Karakiulakis, and Michael Roth. "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?." The Lancet Respiratory Medicine (2020). The “forbidden” drugs. Their generic name ends on “Pril”: captopril, lisinopril, benazepril, zofenopril, perindopril, trandolapril, enalapril and ramipril.
___________

So is the conclusion that losartan, irbesartan, telmisartan etc, is safe during this pandemic?
Or is it best to avoid and switch to something else?
This scientific article was a tad bit confusing to me.

Thanks!

 

[uglevod]

So is the conclusion that losartan, irbesartan, telmisartan etc, is safe during this pandemic?

Officials say that its safe to stay on ARB during Covid(google for more details).

 

[pattismith]

Losartan is an angiotensin II receptor blocker (ARB) drug, and in patients with chronic diseases (such as ME/CFS and sarcoidosis), ARBs are known to cause the symptoms you experienced.

But these symptoms do not occur in people who are generally healthy. In fact ARBs are used by millions of people daily for blood pressure management without any such symptoms.

Prof Trevor Marshall became aware of this phenomenon, and he called the symptoms experienced from ABBs an immunopathology reaction, and theorized that the reaction occurred because ARBs activate the vitamin D receptor (VDR) in cells, and this in turn switches on an immune response which destroys infectious pathogens inside the cell. Thus Marshall believed the immunopathology was a sort of Herx reaction as pathogens in the cells are killed.

He then employed this immunopathology reaction — which he says kills intracellular pathogens inside cells — as the basis of his Marshall Protocol for treating chronic illnesses such as ME/CFS. The MP involves taking the ARB drug Benicar.

More info in this post.

I had the same reaction that @bjl218 had, with worsening of my enthese pains, after the very first pill.

I have a flare of these pains for some weeks, starting two weeks after the flu vaccine shot, but Losartan severely worsened it.

These pains are much less when I take dopaminergic drugs like Methylphenidate, so my hypothesis was that Losartan could have a dopamine antagonist action or a serotoninergic action which could explain worsening of my central pain, and perhaps also my central fatigue.
It happens that I was on the good track, because AT1R is involved in serotoninergic and dopamine systems.

This could explain why losartan is not well tolerated by people with serotonine/dopamine desequilibrum.

Central fatigue induced by losartan involves brain serotonin and dopamine content
Laura H R Leite 1, Alex G Rodrigues, Danusa D Soares, Umeko Marubayashi, Cândido C Coimbra


DOI: 10.1249/MSS.0b013e3181d03d36

Abstract
Purpose: To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise.

Methods: Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex.

Results: Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats.
Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals.
This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue.

Conclusions:

Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus.

Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.

....
Brain Renin–Angiotensin System Blockade Attenuates Methamphetamine-Induced Hyperlocomotion and Neurotoxicity

The renin–angiotensin system (RAS) is a hormone system that is involved in the regulation of the plasma sodium concentration and arterial blood pressure.

It is now well established that the brain has its own intrinsic RAS with all its components, such as Ang II, angiotensin-converting enzyme (ACE), and AT1-R [11]. Brain RAS is involved in the regulation of neuronal function as well as brain diseases, such as Alzheimer’s and Parkinson’s diseases [12,13,14].

Ang II is thought to be a modulator of DA release and plays an important role in the regulation of central dopaminergic neurotransmission [15].

Ang II type 1 and 2 receptors (AT1-R and AT2-R) are expressed in the mesolimbic dopaminergic neurons, and Ang II facilitates dopamine release in the striatum through interaction with AT1-R both in vitro and in vivo [16].

Moreover, AT1-R is highly expressed in DA-rich brain areas [17, 18]. AT1-R antagonist increases dopamine D1 receptor (D1R) but decreases D3R expression [19, 20].
AT1-R interacts with D2R directly, forming functional heteromers in the striatal neurons [21