phase 1 trial of hypertension drug
Posted: Tue Jan 28, 2014 5:05 pm
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http://ccsviinms.blogspot.com/2013/08/m ... blood.htmlWith the growth of research into the connection of MS to cerebral blood flow, we've seen an interest in exploring new ways to address hypoperfusion (slowed blood flow), endothelial dysfunction (damaged blood vessels) and brain atrophy (loss of brain tissue).
Why is this? Because MS specialists, neurologists and advocacy groups are much more comfortable designing, testing and recommending a drug for MS, rather than encouraging healthy lifestyles and treating venous malformations. You cannot monetize or patent a diet, exercise and angioplasty. It's impossible to have a placebo-controlled clinical trial for lifestyle. But you can develop a drug and make a lot of money selling it to a population with a chronic and degenerative disease.
Yowza! 10mg for a little mouse w/EAE! Here's dosage info for hypertension.NHE wrote:Steinman's 1999 paper with lisinopril in EAE used a dosage of 10 mg/kg/day.
http://www.ncbi.nlm.nih.gov/pmc/article ... q14948.pdf
Since I wrote about this topic on FB, I've had several posters come on and say they've already tried Lisinopril, or are on it, and it hasn't helped their MS much. One person even developed the Lisinopril cough, and stopped taking it. This side effect happens in a third of the people on ACE inhibitors...I can only imagine a higher dosage would provoke more side effects.Initial dose: 10 mg orally once a day, in patients not receiving a diuretic.
Maintenance dose: 20 to 40 mg orally once a day.
Some patients appear to have a further response to 80 mg, but experience with this dose is limited.
http://www.aarp.org/health/drugs-supple ... itors.htmlIn this case, the insoluble by-products of the drugs, called kinins, are not filtered out of the blood. They then flow out of the kidneys and lodge themselves in the lungs' bronchial tubes. The coughing spells represent the body's attempt to expel the kinins from the lungs. Even after the drug is stopped, the cough can linger for months until all the kinins eventually find their way out of the lungs.
Lisinopril works on the endothelium and blood vessels.erinc14 wrote:what is the difference between a bp medicine and aspirin ?
http://med.stanford.edu/ism/2009/august/lisinopril.htmlAngiotensin immediately causes blood vessels to constrict. “That raises your blood pressure so when you stand up to get out of a chair, you don’t fall down and faint,” said Steinman, who is also the George A. Zimmerman Professor in the medical school. But angiotensin overactivity causes chronic hypertension. Lisinopril controls blood pressure by blocking an enzyme that converts angiotensin’s precursor into the active hormone. The drug also appears to have certain anti-inflammatory properties.
Lisinopril would be prescribed to people with specific problems, so those problems might have gotten in the way of any benefit of lisinopril on the MS. A controlled study is a good idea, but it's not likely to be a miracle drug. I wish we could see studies of drugs on patients AFTER they've had CCSVI treatment.cheerleader wrote:Since I wrote about this topic on FB, I've had several posters come on and say they've already tried Lisinopril, or are on it, and it hasn't helped their MS much.
That 10 mg dosage was per kg. A mouse wouldn't get the full 10 mg unless it weighed 2.205 lb. That's a big mouse! It's still ~60x higher than the typical dosage for a person though.cheerleader wrote:Yowza! 10mg for a little mouse w/EAE!NHE wrote:Steinman's 1999 paper with lisinopril in EAE used a dosage of 10 mg/kg/day.
http://www.ncbi.nlm.nih.gov/pmc/article ... q14948.pdf
Why would ACE be upregulated in lesions in the MS brain? Maybe venous hypertension? Maybe ischemic-reperfusion injury? both of these situations see the same presentation of ACE upregulation. It's another connection to the vasculature. It doesn't have to point to venous blockages, per se--but it sure makes sense in the CCSVI paradigm.Angiotensin converting enzyme (ACE) and angiotensin receptors are up-regulated in MS lesions in the brain, which suggests a potential link between the angiotensin system and the disease. Lisinopril doses that are equivalent to those prescribed for humans with high blood pressure prevented the development of the paralysis that is characteristic of disease progression in EAE mice and reversed existing paralysis as well.
cheerleader wrote:it's Lisinopril, erin
http://med.stanford.edu/ism/2009/august/lisinopril.html