Colchicine, a clue to why it works so well

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This topic contains 25 replies, has 8 voices, and was last updated by  KeithTaylor 6 years, 10 months ago.

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  • #2661

    zip2play
    Participant

    I was watching an episode of HOUSE, a popular doctor's show in the U.S. starring the brilliant Hugh Laurie (whom I'm sure you Brits are very familiar with.)

    Episode was called “DECEPTION” featuring the also wonderful Cynthia Nixon as a woman with Munchhausen's Disease, a neurosis in which peple FAKE illnesses to get attention and medical care. BUT she also may have aplastic anemia which only House suspects. House wants to biopsy her bone marrow but is not allowed to by hospital administration so she is discharged as whacko and House has a plan to get her readmitted and tested for apalstic anemia. His plan is to inject her with something that will LOOK like aplastic anemia.

    HOUSE:  Colchicine decimates your white blood cells, leaves
              almost no trace.  It's great for faking your way into
              hospitals.

    HOUSE:  I'm going to give you a cocktail of insulin for seizure
              and colchicine to kill your white count.  This will
              absolutely confirm my diagnosis of aplastic anemia.

    She fell into seizures right in front of the hospital and was admitted.

    Okay…what can we possibly draw from this. I got that if colchicine wipes out the white blood count then the immune system will be temporarily shut down and thus, tadaaa, so will an attack on uric acid crystals. Thus, it indicates that colchicine acts VERY differently than pain relievers like NSAIDS, or even codeine, or morphine, oxycodone and hydrocodone. Only cortisone has a similar action directly on the immune system.

    Maybe yes, maybe no…what do you think?

    Hey, who said TV rots the brain.

    #3945

    trev
    Participant

    When I recently told my Doc that Colchicine was an immune suppressant- he said No, it wasn't.

    OK,  an immune killer then?

    This was after the  reaction with a statin drug which are not recommended to go with immune suppressants- so I assumed that was the catch- and it was NOT a good combo!

    I've always thought, though- that it can take a couple of days for the WBC count to drop- so I think your TV plot was using rather a lot of artistic licence, but at the doses you use Zip, maybe not!  Cool 

    PS: If AlloP is doing a good job for you- why the Colch still?

    #3918

    zip2play
    Participant

    Only took colchicine, 2 pills on arising as needed for occasional morning flares/twinges, recently when I lowered my allopurinol dosage to  200 mg. hoping the losartan was pulling its weight. The twinges often followed a hard workout day or an overindulgence in beer. 

    When I confirmed a uric acid back up to 6.7 mg/dL and I went back up to 300 mg./day, where it is obvious I must remain forever, the twinges and the need for cochicine stopped. But I still keep a large bottleful in my larder, just in case.Cool

    Immune suppression is not always a bad thing. Many relatively benign problems are magnified to life threatening by an overactive immune system. Ask anyone suffering from rheumatoid arthritis, Lupus, shingles, or even hay fever or asthma, over-reaction to a bug bite.

    In these and many other conditions the goal of treatment is to atenuate the immune system. 

    Some food for thought is the possibility of using colchicine to ameliorate the symptoms of other immune system caused diseases? (Heck maybe I should work on that for my NOBEL?)

    #3805

    trev
    Participant

    Should that be 'Nobble'  Laugh   -or am I thinking racehorses?

    The negative link between Gout and MS springs to mind-in humans btw, very odd!

    #3877

    Richard Bell
    Participant

    This is something I’ve been thinking about as well. Back in August when I was admited to the hospital because my attack had gotten so bad I couldn’t even get to the toilet on my own it was prednisone that got me out of the hospital. Because my prescription was only enough to last a few days and titrate off in three days I was back to suffering the attack in short order. This pretty much proved that all the pain I was under was my body attacking the crystals in my knees, ankles, feet, Toes, hands,wrists and elbows. Why only in the joints? Is that the only place crystals form? Experience seems to say, yes.

    #3875

    trev
    Participant

    I'm no biologist, but from what I know the crystal growth may need the space afforded in joints by the synovial fluid. If they tried to form in tissue they may have a harder job- as there won't be loads of free UA floating by to attach to the crystal.

    Niether will other cells like the UA and quite possibly allow WB Cells to do their job before the UA 'clumps'..

    A laymans view – what do others think?

    Maybe once tissue elsewhere has been invaded- it then provides a home for UA to deposit [cyst like?] and attacks in joints may then reduce.

    #3765

    zip2play
    Participant

    I think joints are somewhat encapsulated and dont really have the kind of good blood supply other areas of the body have. Hence a lot can go on there that might quickly arouse the ire of the immune system were it to go on in an area with copious blood, white blood cells, platelets, T-cells etc. 

    So urate builds up and up until it is so pronounced it forces contact with the bloodstream and BAM! That's why I think that at the initiation of the first gout attack there is copious urate deposited around the body but just little enough to pass under the radar of the immune system.

    I guess when that elaborate scanning technology becomes common we will learn a lot more about the how, what and where's of tophi deposition.

    #7231

    zip2play said:

    Immune suppression is not always a bad thing. Many relatively benign problems are magnified to life threatening by an overactive immune system. Ask anyone suffering from rheumatoid arthritis, Lupus, shingles, or even hay fever or asthma, over-reaction to a bug bite.

    In these and many other conditions the goal of treatment is to atenuate the immune system. 

    Some food for thought is the possibility of using colchicine to ameliorate the symptoms of other immune system caused diseases? (Heck maybe I should work on that for my NOBEL?)


    Colchicine is already used widely for immune system diseases – familial Mediterranean fever(FMF) springs to mind immediately because of the colchicine crisis debate.

    It has also been mooted as a cancer treatment, but largely discounted because of toxicity at the dose required t be effective.

    Colchicine inhibits microtubules – part of the cell structure that regulates cell division (hence lower white cell count) and signalling functions (hence limiting our immune system call for backup that attracts more white blood cells leading to inflammation and the agonizing pain signals). I hope any lurking microbiologists will forgive my tentative layman interpretation – this cellular level of gout pain and colchicines unique ability to break the cause and reaction cycle is very complicated.

    Perhaps what I should have said is:

    The precise mechanism by which colchicine relieves the intense pain of gout is not known. However, it is believed that the major relief of pain involves colchicine's major pharmacological action: binding to tubulin dimers. Tubulin (MW approximately 10,000 Dalton) is a protein consisting of two forms, alpha and beta. Alpha and beta tubulin form dimers, and these dimers polymerize to form long filaments of microtubules. When colchicine binds to the tubulin dimers, the dimers are unable to form the microtubules. The microtubules are vital for formation of spindle fibers during mitosis and meiosis, intracellular transport of vesicles and proteins, flagella reassembly, ameboid motility, and other cellular processes. Inhibition of ameoboid motility prevents macrophage and leokocyte migration and phagocytosis, thereby presumably preventing the inflammation and pain of gout. Because colchicine disrupts mitosis, halting the process at metaphase, scientists have also evaluated colchicine as an anticancer agent. However, serious toxicities prevent the use of colchicine in antineoplastic therapies.

    With thanks to Department of Medicinal Chemistry at Virginia Commonwealth University
    . Therefore, it is immunosuppressive

    #6939

    zip2play
    Participant

    However, serious toxicities prevent the use of colchicine in antineoplastic therapies.

    I got a kick out of that line. I haave always presumed that most neoplastic chemotherapeutic agents killed ALL cells, with a slightly less fatal rate among healthy cells. After all the first chemotherapeutic agents were variant of mustard gas.

    Cynical old me bets that the reason colchicine is dismissed from consideration by pharmaceutical companies is that it is impossilbe to get anyone to pay $1,000 a pill for it.Wink

    Another take on basically the same info GP has provided:

    Colchicine has been regarded by some as the most powerful anti-inflammatory agent known to man. The beneficial effects of colchicine in the treatment of gout are apparently secondary to its ability to inhibit both the metabolic and phagocytic activity and migration of granulocytes. Colchicine's inhibition of the release of histamine containing granules from mast cells is also believed secondary to its interference with granule transportation by the microtubular system. While beneficial in the treatment of the crystal-induced inflammation observed in gout and pseudogout, colchicine is only occasionally effective in the treatment of other types of arthritides (arthritis).

    #3963

    cjeezy
    Participant

    Just curious, if colchicine kills off white cells, is a person more susceptible to becoming sick with the flu (or whatever) when on the drug? 

    #3965

    trev
    Participant

    I suspect not more likely to catch an illness -but longer to get over it.

    Note, though that virus infections in particular are beaten down by the higher body temperature usually developed. They seem to be programmed not to kill the host as they give up just when winning the battle. Maybe these latest fright viri [pandemic] have a higher withstand.

    I don't think Colch has a temperture lowering function, fortunately- in these cases.

    For bacterial infections there must be a risk of an inefficient immune system needing fairly quick antibiotic support.Something to bear in mind as they are being withdrawn more and more through earlier overuse in viral infections- where they are pretty useless, apart from reducing secondary infections.

    With doctors denying the link it's not surprising that little is known about the immune downsides.

    Most gouties are oldish, not over photogenic [ahem] and grateful for anything!! Frown

    #7289

    cjeezy said:

    Just curious, if colchicine kills off white cells, is a person more susceptible to becoming sick with the flu (or whatever) when on the drug? 


    Once again, cjeezy asks the vital questions that we should all ask, but rarely do.

    I can find little data on this in the ordinary treatment by colchicine, but I have found two particularly interesting though unusual views.

    One paper discusses the role of infection after a young woman tried to commit suicide with 27.5mg of colchicine.

    This paper discusses the role of colchicine poisoning in increasing susceptibility to infections. This aspect is usually under-appreciated in the clinical picture of colchicine overdose.

    Another two papers give an interesting alternative view from studies of colchicine on the infecting invaders. It seems that colchicine also affects the bugs (at least in the case of Toxoplasma gondii and Cryptosporidium parvum), and the mechanism that represses white blood cell replication also represses those infectious organisms.

    Very interesting (to me at least), but it probably has little bearing on the normal application of colchicine for gout pain relief.

    #7290

    trev
    Participant

    Having seen these (or similar) reports a way back made me very wary of going over the limit with Colchicine.

    Also, though I think it could help as a long term prophylactive for gout- the thought of having a compromised immune system 'for ever' didn't appeal , overmuch! Frown

    #7294

    The only long-term prophylactic (i.e. preventative) for gout is uric acid below 6mg/dL. Doctors prescribe colchicine prophylactically during the early stages of urate lowering therapy to prevent pain from uric acid crystals dissolving.

    Simply using colchicine, or other pain killers, as pain prevention does not stop gout. It just masks it so that uric acid crystals continue to build-up until they cause irreversible joint damage.

    #7302

    zip2play
    Participant

    cjeezy said:

    Just curious, if colchicine kills off white cells, is a person more susceptible to becoming sick with the flu (or whatever) when on the drug? 


    I would say yes. That reinforces my ideal use of colchicine as a one day HUGE dose rather than a dribble every day for months.

    Flu is usually mediated by antibidy defenses and probably not affected by colchicine  but bacterial infections which depend on white blood cell and phagocytotic defenses probably are more likely.

    (Oy…27.5 mg colchicine is 55 pills…they must have found her intestines,  tonsils, and brain in the toilet.)

    #7315

    trev
    Participant

    Hyperuricaemia isn't Gout. All people with high UA levels don't all suffer from gout.

    Gout is the bodies' over-response to the high UA and if Colchicine helps reduce or stop an attack- then that is a useful and effective prophylactive. The fact it may have side effects, and serious ones, doesn't alter this fact.

    It does ,of course, imply long co-therapy of diet control etc. to maintain this profile.

    I've seen references to the use of Colchicine long term and in times past -it was the only thing.

    Being based on a plant extract – so not a synthetic drug like AlloP- this doesn't detract from the situation any. I'm not a worshipper of magic bullets , generallly.

    If masking a problem is not helpful- it would explain peoples' ire at badly managed drug therapy!

    #7335

    phofab
    Participant

    6 months ago I asked the Rheumatologist the side effects of the two drugs prescribed, when used over the long term.

    Colchicine – weakens the heart muscles

    Allopurinol – attacks the kidneys.

    This latter observation was also advised to me by a Doctor who discouraged me from using it as a long term remedy, many years ago. It was on the basis that I only suffered the attacks a few times a year and if it was him he wouldn't be taking the drug long term.

    #7347

    phofab said:


    Allopurinol – attacks the kidneys.

    This latter observation was also advised to me by a Doctor who discouraged me from using it as a long term remedy, many years ago. It was on the basis that I only suffered the attacks a few times a year and if it was him he wouldn't be taking the drug long term.


    I'm really curious as to the source off this information. A good friend of mine was left in agony after years of peaceful life on allopurinol, when a new Practice Manager advised that it should be discontinued due to fears of the same risk.

    I have tried to find what this risk is, but only came up with the opposite view – that allopurinol is good for kidney disease.

    Sorry, this is a bit off the colchicine topic, so if anyone has more information about allopurinol and kidney disease, please can you start a new topic.

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