Pulsing INH
I can't tolerate INHi full-time. I'm on Doxycycline and Zithromax, which is going smoothly.
Can one pulse INH+Flagyli if you're not on Rifampin? Or is there some danger in that?
Any thoughts appreciated.
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Hi,
I have been thinking about drug pulsing recently and was planning to post a new topic on this. I think that pulsing drugs is generally not a great idea based upon my experience and the experience of others. I believe that when people stop taking some antibioticsi, they often get more side effects from quitting than from continuing. HOWEVER some drugs such as INHi and Flagyli may be better to pulse than others. I think the reason for this may be a combination of factors that include the half life, action, and minimum inhibitory concentration (MIC) of the drug.
The reason that symptoms seem to increase may be that the drug levels drop below the MIC for Cpni but are still present. The Cpn may have to steal more energy from infected cells through its ADP/ATP exchange mechanism (Cpn are unique in that they use the host cell's ATP) to attempt to pump the drug out of the organism and/or to repair damage being done to it. So during the period of time that the drug levels drop from MIC to essentially 0, the most energy may be parasitized from cells. And the cells lacking energy to complete some normal functions such as hemei metabolism may dump heme precursors (porphyrins) which can cause many of the worst side effects of treatment. If this is the case then drugs with short half lives would be "safer" to pulse and ones with longer half lives would be "unsafe". This certainly appears to be the case in my own and other's experiences so while this is just a theory it does seem to explain this.
Anyway if one were to assume this is correct. The safer drugs to pulse would be INH, Flagyl, and Rifampin and less safe drugs would be Zithromax and Doxycycline.
Drug Half Life
INH 1-3 hrs
Rifam 3 hrs
Flagyl 8 hrs
Doxy 18 hrs
Zithro 68 hrs
- Paul
Paul,
Appreciate the comments. One consideration: Rifampin should probably not be pulsed because it is known to foster persistencei when passed over bacteria repeatedly, that is why it is almost always co-adminstered with INHi and other drugs in TB treatment. At least that's my understanding.
Dr. Stratton had some comments which speculated that INHi might be pulsed with Flagyli. I'm not sure exactly why, although I think it had something to do with the mode of action of INH which is, like Flagyl (although at a different part of the cell process), acts as a free radical to damage the Cpni cell process. However, i can't imagine doing the two together as a pulse, since in terms of side effects the Flagyl/Tinii alone is bad enough, and the INH alone is bad enough.
As noted, Rifamcini should never be pulsed as it engenders persistance readily when not taken continuously. Interestingly Rifamicin is said to block HSP60. I read a study referring to this with Cpn in ankelosing spondelytis. i'll have to dig up the reference.
On Wheldon/Stratton protocol for Cpn in CFSi/FMSi since December 2004.
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral
I'm now doing INHi with Flagyli pulses. I don't feel any worse replacing minoi/zithi with INH, except that I seem to smell worse. I thought I was already a clean fanatic, but now I am showering several times a day. I realized from reading other posts that I need to wash my sheets daily so I won't itch at night. The Flagyl still makes me vomit uncontrollably by the third day of a pulse. Isn't it wonderful to learn these things about someone!
I am two months into antibiotic treatment for fibromyalgiai caused by Cpni. I have lidocain to inject, but I no longer need it. On this first day of a pulse I feel well enough to go to church tonight, but I think I may stink too much.
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
Janice- Flagyli also made me very nauseated. I switched to Tinidazole which is much more tolerable in this way, although much more pricey. Given the amount one takes on a pulse, worth it!
On Wheldon/Stratton protocol for Cpni in CFSi/FMSi since December 2004.
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral
As noted, Rifamcinii should never be pulsed as it engenders persistance readily when not taken continuously. Interestingly Rifamicin is said to block HSP60. I read a study referring to this with Cpni in ankelosing spondelytis. i'll have to dig up the reference.
Hey Jim,
With a half life of 3 hours you are pretty much "pulsing" Rifampin with a single daily dose. It seems that what you really should not do is take it alone. As to blocking HSP60... well, that kind of thing reallly sets me off... far too often erroneous conclusions are drawn from data (I should note here this does not bother me near as much when I am the one jumping to erroneous conclusions.)...
It is established that persistent Cpn release HSP60. It is also established that Rifamycins have bacteriocidal action against persitent Cpn. So If you take those together Rifamycins may not actually block HSP60 but kill the organism producing HSP60. BTW HSP60 is a protein that Cpn produces that is highly antigenic. It produces a significant immunei response including inflammationi, vasodilation, and fever.
- Paul
This one is an old one, and I haven't gone to the references used to see how the HSP60 was understood as blocked, but here it is (I've underlined the related sentence):
http://www.jrheum.com/abstracts/abstracts04/1973.html
Doxycycline versus Doxycycline and Rifampin in Undifferentiated Spondyloarthropathy, with Special Reference to Chlamydia-Induced Arthritis. A Prospective, Randomized 9-Month Comparison
JOHN D. CARTER, JOANNE VALERIANO, and FRANK B. VASEY
ABSTRACT.
Objective. Chlamydia is a known trigger of reactive arthritis (ReA). It may also be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent, metabolically active, Chlamydiae have been observed in the synovial tissue of these patients years after their initial exposure. Trials with lymecycline and rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro data suggest that persistent Chlamydia become resistant to chronic monotherapy of tetracyclines or rifampin, whereas no such resistance is noted when rifampin is added to antimicrobials that are active against Chlamydia. Rifampin and doxycycline also show synergistic effect against Chlamydia. In addition, rifampin inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key role in the chronic persistent state of Chlamydia. We conducted a prospective, randomized 9-month trial to evaluate the efficacy of doxycycline versus a combination of doxycycline and rifampin in the treatment of uSpA.
Methods. The study enrolled 30 patients with chronic inflammatory arthritis (average disease duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group criteria, with no evidence of inflammatory bowel diseasei, psoriasis, ankylosing spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po twice daily or a combination of doxycycline 100 mg po twice daily and rifampin 600 mg po daily. They received a 4-question self-questionnaire and a blinded joint examination at each visit. The questions include a visual analog scale (VAS) for their current amount of back pain, duration of morning stiffness, back pain at night, and peripheral joint pain. The blinded joint examination consisted of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined as those who improved ≥ 20% in at least 4 of the 6 variables at 9 months of therapy.
Results. Comparing the doxycycline + rifampin arm (D/R) versus the doxycycline arm (D) at 9 months of therapy, all 6 variables improved more in D/R versus D, 4 of which were statistically significant. The mean VAS (scale of 100) decreased 24.4 points in D/R in contrast to 3 points in D (p < 0.03). Duration of morning stiffness decreased by 1.2 h in D/R, with a slight increase of 0.1 h in D (p < 0.003). The back pain at night and peripheral joint pain both improved in D/R group versus D (not statistically significant). Finally, the SJC and TJC also improved in D/R (–2.1 and –2.5) versus D (–0.4 and –0.6; p = 0.02, p = 0.03, respectively). Eleven of 15 patients in the D/R arm were responders, whereas only 2 of 15 D group patients were considered responders (p < 0.003).
Conclusion. The combination of doxycycline and rifampin for 9 months seemed to be effective in treatment of chronic uSpA. This is the first study to demonstrate therapeutic benefit with antimicrobials to a chronic inflammatory arthritis possibly secondary to persistent Chlamydia. (J Rheumatol 2004;31:1973-80)
On Wheldon/Stratton protocol for Cpni in CFSi/FMSi since December 2004.
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral
Hi Jim,
That is a really nice find. I wish they had gone one step further and done a rifampin only arm although that may have been irresponsible because as you noted it is easy to develop resistance to rifampin alone. I was not aware that those two drugs are used together but Dr. Stratton says they work synergistically. Based on this I am probably going to add rifampin some time in the future.
- Paul
Paul- if you get the original article, or get Chuck to obtain it, pass it on. I couldn't find any references in pubmed on rifamcini blocking HSP60, so I'm curious what they cite to support that notion. Everyone who takes rifamcin says they get "hammered" for a bit, so it doesn't seem like this blocking effect has much subjective impact on symptoms, although it may prevent localized cytokinei damage if it's significant enough.
On Wheldon/Stratton protocol for Cpni in CFSi/FMSi since December 2004.
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral