No new ideas

I called the Lyme doctor's office, and she called me back between appointments. Unfortunately, she didn't have any viable alternative to amoxicillin to suggest. She didn't want me to increase the dose of amoxicillin, since it's already making me ill; however, at this low dose, it's questionable whether it will be useful for treating the dental problems. She wanted me to try taking the probenecid again in a half dose, but I politely declined -- twice -- citing hives. When that didn't work, I just refused. If she prefers to think I have an inexplicable prejudice against probenecid, rather than a legitimate allergy, that's okay with me. Everything I learned in immunology told me that it's not a smart idea to take additional doses of a drug after you have had an allergic reaction to it. Hives = allergic reaction, so no.

I woke up multiple times again last night. I have had a headache since I started taking the amoxicillin on Friday. I also developed a full-blown yeast infection over the weekend. Oh -- and, of course, my teeth still hurt. Result: I am now cranky cubed. I think I'm going to discontinue the amoxicillin for now. I have an appointment on Monday with a possible alternate Lyme doctor, so I will ask her about it then.

Of teeth and typhoons

Remember a couple of days ago when I was feeling paranoid about taking my new meds? Of course you don't, because I forgot to write about it here.

Background:
On January 20, I went to the dentist to get my teeth cleaned. Thanks to all the dental problems I have had since the Lyme first made its presence known, and the fact that no visit to the dentist ends well anymore, I now have major issues with going to the dentist. On 1/20, I saw my 4th new dentist since 2004.

After the hygienist had taken x-rays and cleaned my teeth, the dentist came in to look them over, and asked me what the story was with the two missing lower right molars. He even said that it looked like I took good care of my teeth and shouldn't have any missing, or something like that. I don't think I have mentioned the molar story here, so I will give you the high points: pain for months with no sign of decay whatsoever, followed by 2 root canals that didn’t help and 16 days of Cipro, followed by 4 years of intermittent pain, multiple night guards, and many many visits to the dentist with normal x-rays and lots of shoulder-shrugging, then suddenly WHAMMO -- abscess and extraction, followed by 3 rounds of clindamycin, followed by continued pain, degeneration of the roots of the second molar and another extraction 4 months later. I still have pain on that side of my jaw where the teeth used to be and also under the next tooth in line. I tried one last night guard after the second extraction to keep my upper molars from descending. Due to my latex allergy I can now only have hard night guards, and my new night guard made my jaw pain worse. I went back to using my old NTI-TSS device, which fits over my front teeth only.

Back to the present: when the dentist asked about the missing molars, I mentioned that I had recently been experiencing some pain in two teeth on the other side. He did a percussion test and discovered not two, but four molars on the left side that were affected -- two on the top and two on the bottom. He did a very careful visual exam of my teeth, tested them for cold sensitivity (normal) and then took extra x-rays so he could look at the roots. Once again, there was absolutely no sign of decay. I got a horrible feeling of déjà vu.

The new dentist agreed with the other dentists I had seen since my Lyme diagnosis that Lyme disease could be responsible for my recent dental problems. He also strongly agreed that I shouldn't have any implants placed until the infection was completely resolved. He was very concerned and wanted me to see a neurologist, but I had received no help from neurologists for my dental problems in the past. So, I took the problem to my Lyme doctor. I mentioned that the new left-sided dental pain had started after I stopped taking the Lyme antibiotics and switched to the Babesia treatment, and that at the same time, my right shoulder had frozen up again. Ergo, I seemed to have two different infections that don’t respond to the same drugs. She agreed, and prescribed amoxicillin and probenecid to see if they would help with the joint and tooth problems. Probenecid is used as an adjuvant to amoxicillin because it blocks metabolism of amoxicillin in the kidney. People who take probenecid with amoxicillin can thus take a lower dose of amoxicillin. Nifty, right?

Back to the present:
Not nifty. I had an adverse reaction to the probenecid in the amoxicillin/probenecid combo: severe nausea and dizziness (think “typhoon on the high seas”) with headache and hives on my jaw and abdomen. The reaction lasted 8 hours, so I spent Friday on the couch trying to lie as still as possible and wishing I could puke. I skipped my Friday evening dose, then did a control test yesterday by taking just the amoxicillin without the probenecid (they are in 2 separate capsules). I had no nausea, dizziness, or hives, so I think I have identified the culprit. Of course, the amoxicillin is not side-effect-free either -- on Friday night I woke up twice, but last night I woke up some crazy number of times -- 5 or 6. So I am tired, cranky and irascible. Bah! Effing meds! Effing bacteria! Grr!

I'm going to call my Lyme doc tomorrow to see if there are any other alternatives.

Herxing again

I haven't been keeping very good track, but I'm herxing again tonight. Drenched in sweat, alternately baking and shivering, and have had a headache off and on all evening. It has been happening quite often -- not quite every night, but almost. Interestingly, it happens much more often at night after my 8PM dose than in the morning.

hormones, cont'd.

I found a BHRT doctor! Really. I did a search on Project Aware to locate the nearest compounding pharmacy that does bioidentical hormones, and this morning I called the pharmacist to ask for a local doctor referral. He knew of three. I called the first one on the list, and she had an opening on February 2, so I took it. I made sure to tell her that I was looking for a doctor who did BHRT, and she said “You have come to the right place!” Here’s hoping. As one of my friends said, "It’s like you have to complete a maze or something to find the right person to help. 'You have successfully completed Level One! Your new power is the ability to have your hormones tested!'"

In case the doctor wants to check my baseline hormone levels, I decided (regretfully) to wait until after my visit to start using the progesterone cream. That means I'll have one more episode of mood swings to deal with. Hopefully it will be the last.

mood swing update

I had an appointment with a reproductive endocrinologist on Monday. She agreed with my psychiatrist that my mood swings are linked to my ovulation cycle. So, the next thing I'm going to try for my mood swings is progesterone. The big question has been what form to use. The endocrinologist offered me Implanon or Depo Provera shots. I was reluctant to try Implanon because of my multiple adverse reactions to plastic IVs (the "container" is a small plastic rod) and because I get hypertrophic scars; the doctor was reluctant to let me try Depo Provera because of my multiple adverse drug reactions (it's non-reversible and lasts for 3 months). Progesterone-only birth control pills are out because my blood pressure now spikes when I take BC pills.

I asked the doctor if she had any experience with bioidentical hormones, and she said no -- that it might be useful, but that she didn't know anything about the bioavailability or dosing. She said I'd probably need to block ovulation to get rid of the mood swings, but I'm wondering.

So I decided to try bioidentical progesterone. I found one called Progestelle that is available OTC. It only has 2 ingredients -- USP bioidentical progesterone from yams, in a base of fractionated coconut oil. (It is also available in other base oils, for those with a coconut allergy.) I already know that I'm not allergic to coconut oil, and the fractionation means that it remains liquid and has an indefinite shelf life. Very cool. Apparently the bioavailability of progesterone when it's used topically is very high; unlike oral forms, it bypasses the liver and goes straight into the bloodstream. The one I bought has 800 mg progesterone per ounce. My first order came today. It's used on days 6-26 of your cycle, so I'll be starting it in a couple of weeks.

I also put in a referral request at the Women's International Pharmacy for a doctor who is experienced with bioidentical hormones. I didn't realize such a doctor would be so hard to find.

In the meantime, I have been reading up on Xenoestrogens and how they can affect the body's estrogen and progesterone levels. Not pretty. Even just reading the abstracts has me reconsidering several products I have been using for years.

The Malarone/coQ10 question

I stopped taking coQ10 when I started taking Malarone according to my doctor’s instructions. Unfortunately, it turned out that my 400 daily mg of coQ10 was what was working for my migraines -- they have come back since I stopped taking it. I have been having a mild one almost every day, and yesterday I had a seriously bad one. Last night, I decided to make it my mission to find out whether the coq10 ban was really necessary.

I had one clue that it might not be -- a post from a Lyme doctor in Germantown, MD who maintains a public blog about his experiences treating Lyme and its coinfections. In a post from 2008, he said that

Atovaquone…also appears to work through a mitochondrial mechanism. It interferes with electron transport- the final stage of the KREBS cycle necessary for cellular energy production. This is considered a possible mechanism of action. It does not involve the coenzyme Q10 pathway. And even if it did, it inhibits an enzymatic conversion in the cell. It’s effect would be independent of the amount of Q10 present. And furthermore- there is nothing to suggest that oral Q10 supplements would have any way of getting into bacterial mitochondria.

Q10 and Mepron both have effects in the mitochondria of cells. That is all they have in common. They work on different cellular mechanisms. If Q10 is an effective supplement for Lyme symptoms, then there is no scientific rationale for stopping it when anti-Babesia therapy is prescribed.

I know this contradicts advice I have given patients in the past. But not having the time to research every recommendation, I had taken this on faith. I think it was incorrect advice.

I spent several hours last night and most of today researching it. Here is what I found:

A synthetic analog of ubiquinol, or coenzyme Q10, atovaquone is a broad-spectrum antibiotic with an elimination half-life of 2-3 days in adults. Atovaquone selectively inhibits protozoan mitochondrial electron transport at the cytochrome bc1 complex and collapses mitochondrial membrane potential (Mather MW et al, 2007). It binds to the complex's cytochrome b subunit, specifically to the ubiquinol oxidation pocket, where it interacts with the Rieske iron-sulfur protein (Kessl JJ et al, 2003).

Ubiquinol binds both to the oxidation pocket and the Rieske protein (Wikipedia, “The Q cycle”, no reference). Normally, ubiquinol then participates in a redox reaction with ubiquinone, which binds to a nearby site on the cytochrome b subunit. As part of this reaction, ubiquinol gives up an electron to the Rieske protein, which then passes it on to the cytochrome c1 subunit of the complex (Zhang Z et al, 1998; Crofts AR et al, 1999). There’s a second half to the Q cycle, which you can read about here.

Although Atovaquone and ubiquinol bind to the same sites on the cytochrome bc1 complex, they use different binding residues. When atovaquone is bound, though, it blocks movement of the Rieske protein domain by locking the protein in its cytochrome b-binding conformation, preventing the electron transfer I described above (Mather MW et al, 2005). Without the electron transfer, the Q cycle cannot be completed; thus, no need for ubiquinone…

…in bacterial mitochondria, at least. I still need it to keep my cranial blood vessels happy. It did occur to me to wonder if ubiquinone participated in any other mitochondrial reactions. It does, but since atovaquone collapses mitochondrial membrane potential I can't see how it could get in. And, as far as I can tell, even if it gets into the bacterial mitochondria, it won’t matter, thanks to Malarone's super-long half-life .

So I started taking it again. I feel a bit like a renegade, and also insecure about my biochemistry memory, so I’m going to take the coQ10 2-3 hours away from my Malarone doses (not that that will make any difference, given Malarone’s long elimination half-life -- it will either be a problem, because there's something that I've missed, or it won't). Since the Malarone has been giving me what I think are Herxheimer reactions every few days, I’ll watch to see if the Herxes stop with the addition of the coQ10. If they do, then I’ll discontinue it and start looking for another functional migraine remedy.

FUN! Wasn’t that fun? I LOVE SCIENCE. It gave me a huge rush to get even this far in understanding how this works.

Am I herxing?

I think I have been herxing. Several times since starting it I have either woken up boiling hot and sweating (to the extent that I had to throw off the covers and the pajamas and socks I usually sleep in, in my frigid bedroom) or had spells of similar sweating or chills during the day. I have taken my temperature during the chills and found it to be 97.1 (my "normal"). Dr. Z told me some time ago that this could be from HPA axis suppression.

When I woke up early this morning, in addition to the sweating, I had shooting pains in my legs and feet and my muscles were all tensed up. I concentrated on my breathing, and after about an hour was able to relax enough to go back to sleep. It reminded me that I should write it down, though.

Another thing I keep forgetting to write down -- my right shoulder is freezing up again. I suspected it a few days ago, and now I'm having trouble reaching behind myself to shrug off a coat. I'm hoping that getting up to the full dose of Malarone this weekend will help; if not, I need to mention it to Dr. M when I see her on 1/24.

note to self:

Don't walk two miles when you have plans -- any plans -- the next day.

I walked to the hospital and back for my mammogram yesterday. I had planned only to walk there, and then to take a cab back. There was a cab in the cab rank right by Barns & Noble, but it was such a nice day, and I wasn't in too much pain yet...

By the time I got home, I could barely move. I sat down to rest and didn't get up for hours. It seemed like I kept feeling more, not less, tired. When I finally stood up to make dinner, I felt weak and shaky, with pain in all my weight-bearing joints and full-on fog brain. On and off for the rest of the day yesterday and today, I have had a migraine with left eye pain and what seems to be blurry vision -- general inflammatory symptoms, for me. I am seriously, non-functionally exhausted.

I wish I didn't love walking so much. I miss, not just being out in the world, but moving through it under my own steam.