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Posted: Thu Nov 17th, 2005 21:19 |
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Why and when do you recommend taking minocycline frequently?
How minocycline works
"The MP antibiotics weaken the bacteria, allowing the immune system to kill them. But the same antibiotics that block the ability of the bacterial ribosome to create proteins, and thus weaken them, also have a modulatory effect on the immune system itself. This has never been defined in any papers I have seen, but is likely when we consider that most of the antibiotics have come from a parasitic source - mino from a strep mutant, etc. It would be folly to assume they have no effect on the host.
The exact reason why high-dose, and high-frequency, minocycline behave differently from low-dose, pulsatile minocycline is still elusive. The best guess I can give right now is that demeclocycline was originally isolated from a Strep mutant species, and minocycline is minimally modified from demeclocycline only by the substitution of a chlorine with a methyl group. I am thinking it is possible the body's innate immune system sees the antibiotic as being pathogenic in some way, and reacts accordingly, reducing its ability to kill the intra-phagocytic bactera. This is more of a problem at high dose antibiotics."
Dr. Marshall, PhD
Minocycline use as an NSAIDs
According to Guidelines for the Management of Rheumatoid Arthritis minocycline is used as a DMARD (Disease Modifying Anti-Rhuematic Drug), NOT for it's anti-infective properties. The dose they use is 100mg twice daily. In this lengthy document only one short paragraph is allocated to the use of 'tetracyclines'. It cites one study that demonstrated improvement with the use of minocycline but states "further research is necessary to define the exact role of tetracyclines in the treatment of RA. By "improvement", they mean fewer symptoms of inflammation.
Minocycline, as most rheumatologists know, has an anti-inflammatory effect at standard doses.http://tinyurl.com/dxuw2 The usual palliative dose to reduce Rheumatoid Arthritis symptoms is 100mg twice daily. It is not known just how minocycline works to reduce inflammation and pain but it is commonly ordered as an NSAIDs (non-steroidal anti-inflammatory drug) by rheumatologists in conjunction with other palliative pain medications. This palliative use for pain reduction is the only accepted use of minocycline by the American Rheumatology Asssociation. The antibiotic effect of minocycline is thought to be irrelevant to rheumatic diseases because they are not accepted to be caused by intracellular bacteria.
Dr. Marshall’s pathogenesis of Th1 inflammation describes how intracellular bacteria triggers the abnormal immune system response that causes many inflammatory symptoms, including joint pain. Minocycline’s antibacterial action weakens the intracellular bacteria only when the tissue level of minocycline is falling (decaying) between doses. It is then that the immune system is able to identify and kill the intracellular bacteria. If the tissue level remains high as it does in the standard dosing, little intracellular antibacterial action is evident although some persons will report adverse symptoms to the standard dose of minocycline that are highly suggestive of a immunopathology and undiagnosed Th1 inflammation.
Dr. McPherson Brown’s Roadback protocol is based on the same premise that intracellular bacteria cause RA and it uses Minocin 100mg every other day. This allows the minocycline tissue level to fall and weaken the bacteria. For many people, that has been an effective method to kill intracellular bacteria (as evidenced by immune system reactions) and reduce inflammation to some degree. Most people, however, do not consider it a cure and do not have complete resolution of their RA symptoms.
The Marshall pathogenesis describes how Benicar blocks angiotensin to allow the immune system to function normally and thus much more effectively kill the intracellular bacteria that are weakened by the decaying minocycline in the tissues. This can result in unexpected immune system reactions that are too severe to tolerate.
Stopping or reducing the minocycline often stops the immunopathology.
When immunopathology continues without minocycline
But sometimes, the immune system continues to function very effectively, killing large amounts of intracellular bacteria even without minocyline in the tissues. In that case, we have learned that by using frequent, minocycline dosing, minocycline functions in its role as an NSAID. This is because maintaining a constant level of minocycline in the tissues doesn’t weaken the bacteria and this usually relieves the intolerable immunopathology. Minocycline elicits the maximum immune system response as its tissue concentration decays away to zero, so increasing mino frequency, although seeming counter-intuitive, actually dampens immune system reactions best.
The Benicar blockade is continued for its own unique anti-inflammatory effect and a low dose of 25mg of minocycline taken every six or 12 hours is most often a high enough dose to maintain a constant tissue level and thus relieve intolerable Herxheimer symptoms. Dr Marshall suggest keeping to a maximum of 100mg minocycline total per day with Benicar.
The frequent mino dosing is a temporary palliative measure. As soon as the intolerable immunopathology subsides, the interval between doses is gradually lengthened to eventually reach the desired every 48 hours interval.
In short:
-High dose, frequent minocycline acts as a palliative, mild NSAID in inflammatory diseases.
-Low dose, pulsed minocycline weakens intracellular bacteria and is especially effective when a Benicar blockade is in place.
-Low dose, frequently dosed minocycline can act as an NSAID to relieve an intolerable immunopathology.
How can I determine when frequent Minocycline dosing is most likely to reduce immunopathology?
When uncertain what to do when trying to reduce symptoms, it is probably best to first try reducing the Minocycline dose and/or delaying the next dose before trying frequent mino dosing.
If that doesn't seem to be working and you find your symptoms remain intolerable, you can always take a dose of Minocycline, and then, if you choose, try the option of frequent mino dosing.
Frequent Mino may not reduce symptoms if your immune reaction on the two days following a dose of minocycline is:
a) not very different from one day to the next
b) lacks a consistent pattern
c) or is strongest at the beginning and end of the 48 hour cycle.
In these cases, frequent Mino might help at first but then may cause increased symptoms later (possibly different symptoms than experienced before).
Your reaction pattern (first day vs. second day) may change over time as well – you should always judge by your current pattern.
For people whose immune system reaction starts within a few hours after a dose of Minocycline and is stronger on the first day (first 24 hours)
- taking frequent Mino may be unlikely to reduce a reaction that is too strong and may increase symptoms.
- reducing or delaying your next Minocycline dose may be more likely to reduce your reaction.
For people who find their symptoms are significantly stronger on the second or third day after taking a dose of Minocycline
- frequent Mino dosing may help reduce symptoms when they are too strong
- take Mino 25mg every 6 hours
- or take Mino every 12 hours
- or take Mino daily
- (for those already on higher Mino doses) take 50mg every 12 hours or daily
Note: The above conclusions were based on reports of 26 members and their patterns were quite consistent, though there were occasional exceptions. For instance, some people could reduce their reaction by lowering and/or delaying their Minocycline dose -- even though they reacted more on the second day. And frequent Mino dosing helped some people with fairly constant reactions.
Using low-dose, high frequency minocyline to palliate the prednisone weaning process
This same antiinflammatory effect of frequent minocycline dosing may be needed to reduce the increased inflammation that sometimes occurs during the steroid weaning process despite the use of a tight Benicar blockade.
When the weaning process is complete and symptoms are tolerable, the interval between doses is gradually lengthened to eventually reach the desired every 48 hours interval.
Related information:
How can I manage immunopathology?
My immune response / symptoms are too strong. What should I do?
Immunodepression and Anti-Inflammatory Activity of Antibacterial Agents
Why do we take minocycline only every other day? Why do I feel worse on the second day? What time of day should I take it?
Last edited on Sat Oct 6th, 2007 11:12 by Foundation Staff
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Aussie Barb
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Posted: Wed Feb 1st, 2006 09:44 |
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Circumstances that might warrant use of frequent, low dose Minocycline
There are particular circumstances when a Member is advised to begin frequent low dose Minocycline to prevent intolerable herxing / symptoms. frequentminocircslink
Please ask on the Board for special assistance for your circumstances.
When you have been taking minocycline prior to beginning Benicar and the MP:
Continuing frequent low dose mino is the safe and tolerable option while you begin the Benicar or if, in other circumstances you are already taking the Benicar. eg to wean Steroids.
If you are coming from a pre MP pulsed Mino schedule: To dampen any potential herxing which may occur when decreasing the mino dose,
it is best to continue taking the mino but at the same time as you begin the Benicar, you will need to change the dose and schedule of your mino. read on.
As soon as you have your NoIRs and your home protected and you are ready to begin diligently avoiding Light and D, and your Dr gives the go ahead, you may begin Benicar:....
You may begin by taking the mino as a 25mg dose Q6H ie. every 6 hours. at the same time as your Benicar.
The maximum recommended daily total mino to be taken with the Benicar is 100mg only.
Taking 25mg of minocycline every six or 12 hours often relieves inflammatory symptoms that are intolerable.
Why and when do you recommend taking Minocycline frequently? (the post above) because a constant level of Minocycline has an anti-inflammatory effect, not an antibacterial effect.
Continue at this dose and schedule till you feel you are stable enough to extend the dosing out gradually to QOD (ie every other day) dosing without pushing yourself to tolerate symptoms.
Any dosing / schedule that works for you to dampen your symptoms may be used.. that may be the dose taken once Daily or divided into twice per day, or into Q6H (every 6H ie hours)
Nighttime Mino dosing: arrange your dosing to be least disruptive.. and have the meds and water bedside so you dont have to get up.. some just wait till the need wakes them rather than set an alarm thru the night.
By adjusting the medications you are gaining the flexibility required to balance all tolerably, learning by your own experience how the MP works, learning how to control your symptoms / Herxing before proceeding to the antibiotic combinations in Phases II and III. The Board Staff is available to help you.
Make sure you are having adequate rest. By pushing our bodies to the limit of tolerable herxing we are working our body to capacity.
Keep all Herxing at a tolerable level for you. Do not 'push' the intolerable Herxing. Dr Marshall wrote: There is no point in pushing your body too hard, and you might do damage to it.
You will not be slowing your healing by keeping Herxing tolerable. Tolerable Herxing is essential for Safety and Efficacy of the MP.
See Immunopathogy (Herx reaction) What is it?
You will learn by experience what is herxing and what are your inflammatory symptoms, and how to adjust your medications accordingly.
My immune system reaction is too strong. What should I do? ..
Do not hesitate to use any of the meds adjustments.
Check these options one at a time to assess and adjust your own situation. << if having problems please check if you need to make adjustments in any area, and feel free to ask on the Board. thank you.
If you are concerned do not hesitate to contact your Dr.
____________________
Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| Depression| 24+ years not Dx| MP Aug04| ABC of MP| MP Search|
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Aussie Barb
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Posted: Fri Feb 24th, 2006 07:43 |
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(filelink)
It is the patient's responsibility to see that the prescribing doctor is following the MP correctly.
Please check all precautions / instructions in the Phase One Guideline with your Dr. Some have it printed to check with regularly. It is very important that you and your Dr know to follow the essential aspects and guidelines as written for safety and efficacy of treatment..
1. When your Doctor orders Benicar, we recommend asking s/he to Rx Minocycline at the same time, to have in hand for use when required.
Having the Minocycline available ready to use will allow you to adopt this low dose, frequent dosing regime in any situation that it is required to dampen herxheimer reaction, as soon as it is required, for your safety.
Taking 25mg of minocycline every six or 12 hours often relieves inflammatory symptoms that are intolerable.
Why and when do you recommend taking Minocycline frequently? (as above)
Meg Mangin R.N. wrote:
Unfortunately, it's not uncommon for a doctor to agree to support a patient on the Marshall Protocol without fully understanding all the ramifications.
Somehow you need to impress on your doctor that you must follow the MP exactly if you are to be safe. Your doctor is responsible for your welfare. Please refer your Dr to the Information above.
Even if you do not develop a dangerous cardiac arrhythmia or serious respiratory distress, see What is a cardiac Herx? When should I be concerned, if your your symptoms are barely tolerable, continuing the protocol will be difficult if Dr doesn't support the usual methods of managing the Herxheimer reactions, and using frequent dose minocycline is a valuable tool.
If Dr needs reassurance, encourage him/her to call Dr. Marshall.
Your return to health depends on your ability to actively advocate for your recovery with the MP.
____________________
Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| Depression| 24+ years not Dx| MP Aug04| ABC of MP| MP Search|
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Foundation Staff
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Posted: Fri Mar 17th, 2006 21:10 |
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Using high dose minocycline to treat RA
(filelink)
When someone with severe, long-term RA starts the Road Back Protocol, 200mg MWF or the Harvard Protocol, 200mg daily, they often feel much worse for months, then begin improving. It took me about 8 months on that protocol to be certain that I was improving. It takes some people 12 or more months. During that interval it makes the disease unstable, good days and bad days, good weeks and bad weeks. It isn't like the predictable, reliable herxing on the MP, but I believe it is herxing nonetheless. While it seems to be true (from my experience) that Minocycline shuts down the immune system, it also is pretty rough on bacteria. I suspect that in my case the dominant effect in the early months was anti-bacterial, when I had a very heavy load of bacteria. I think the dominant effect gradually switched over to anti-inflammatory or immune suppression as the months wore on. I got tremendous relief from that protocol but ultimately switched to the MP to see if I could could move to a full cure. I was pretty much pain free when I started the MP last September, but I started a whole new round of herxing when I started the MP.
My point to all of that is that it seems to be very normal to herx on 200mg of daily Minocycline if you are very sick.
John McDonald
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