'Strongest Evidence Yet' Links Anticholinergic Drugs, Dementia

[LA18]

I’m scheduled for a glaucoma test next week and asked for a list of the drugs they use as part of this procedure. Of course the drug that dilates the pupils (tropicamide) is an anticholinergic, which I probably should have known. Given my APOE status (E4/4), and my current health issues, I’m concerned about this. The drug’s side effect profile indicates that it is likely absorbed at a level that can be problematic in vulnerable populations. I am just wondering how others have handled this (has anyone had this type of exam recently?) and whether I’m being overly cautious, as this would only be a one-time exposure. I plan to call the doctor to see if there are other options, but there may not be in this case. I had elevated eye pressure a couple of months ago on the standard (air puff – sorry for the nonscientific terminology here) test.

[Stavia]

Lac, a once off is unlikely to doom you. I believe we are not as fragile as that. You need your eyes.

[rep]

I agree that once is unlikely to cause a problem.

But, you do have alternatives. My doctor uses an Optomap machine. I never get the dilation drops.
Here are a couple sites that mention it:
http://www.wingeyecare.com/Services/Opt ... u0vzj.dpbs
http://www.drgaryjacobs.com/optometry/o ... -glaucoma/

I have to pay an extra $30 out of pocket to have this done rather than the dilation but it is worth it to me.
You'll probably have to call around to find an office that has one.

[LA18]

Stavia, rep, thanks for the feedback. I will definitely investigate the other options, but if they’re not available in my area I may just go with the current plan. I know I’ve had the dilation before, with no noticeable side effects. I’m just highly paranoid about cognitive decline these days, given my 4/4 status and some recent symptoms.

[PhillyFree]

PEMT rs7946=TT here (along with 56% of others with Euro ancestry)

I've been aware of choline to offset risk of fatty liver for a few years now.

So I eat 3 eggs about every other day,
and use 1 scoop of Solgar brand (non-GMO soy) Lecithin in my morning smoothie.

[circular]

Back to Ketotifen, part antihistamine part mast cell stabilizer ... It's one that initially can cause drowsiness but the affect wears off. I would assume if the drowsiness indicates crossing the BBB that it should continue to cause drowsiness?

The initial week of daytime drowsiness on Ketotifen is long gone, but I do find it helps my sleep a lot (possibly by lowering excess histamine in my brain), which is crucial, since I've had about seven years straight of significant sleep issues. I also have much better daytime energy. So this may be a risk/reward thing and of course don't take more than one needs. I keep coming back to that I haven't had time to research histamine in the brain, which has got to be a very complex picture with goods and bads and balances and no way to know empirically what's going on in there, with or without antihistamines? When do we know that a person has too much histamine detrimentally affecting their brain which overrides anticholinergic concerns up to the lowest effective dose?

(The above is currently modified by the fact that spring pollens are knocking me off course again and I'm not getting enough meds to deal with that too.)

Also my doc wants me on an H2 blocker as well and recommends Zantac, standard recommendation for mast cell issues. I'm cautious to add another possible anticholinergic; however, I find this, rather old from 2000:

Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat.


"Abstract
Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances, cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat stress in a rat model was examined using the pharmacological approach. Blockade of histamine H2 receptors by cimetidine or ranitidine significantly attenuated the BBB permeability to Evans blue albumin and [131]I-sodium extravasation, brain edema formation and cell injury following 4 h heat stress in rats at 38 degrees C. These drug treatments also restored the CBF to near normal values. These beneficial effects in heat stress were most marked in rats treated with ranitidine compared to cimetidine given in identical dosage. Our observations suggest that blockade of histamine H2 receptor is beneficial in hyperthermic brain injury and indicates that histamine is involved in the pathophysiology of heat stress induced brain dysfunction. Our study strongly suggests further need to develop more specific and sensitive histaminergic H2 receptor blockers for the treatment of neurological ailments." http://www.ncbi.nlm.nih.gov/pubmed/1145 ... $=activity

Now last I checked I'm not a rat (I'll triple check that later,) and I'm not sure if this is comparable, but I have low heat tolerance, and my mind goes mushy when I get too hot, which is before others do... "histamine is involved in the pathophysiology of heat stress induced brain dysfunction".

Another question I'd have is whether high histamine levels in the brain have some direct affect on the cholinergic pathways. Maybe they are procholinergic so some anticholinergic effect in the brain could be desirable in some?

So I think this issue of histamine and H1/H2 blockers may be very complex when it comes to the brain?

Then there's this, 2013:

Am J Alzheimers Dis Other Demen. 2013 Jun;28(4):327-36. doi: 10.1177/1533317513488925. Epub 2013 May 15.
The neglected role of histamine in Alzheimer's disease.
Naddafi F1, Mirshafiey A.
Author information

Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques accumulation and cognitive impairment. Both environmental factors and heritable predisposition have a role in AD. Histamine is a biogenic monoamine that plays a role in several physiological functions, including induction of inflammatory reactions, wound healing, and regeneration. The Histamine mediates its functions via its 4 G-protein-coupled Histamine H1 receptor (H1R) to histamine H1 receptor (H4R). The histaminergic system has a role in the treatment of brain disorders by the development of histamine receptor agonists, antagonists. The H1R and H4R are responsible for allergic inflammation. But recent studies show that histamine antagonists against H3R and regulation of H2R can be more efficient in AD therapy. In this review, we focus on the role of histamine and its receptors in the treatment of AD, and we hope that histamine could be an effective therapeutic factor in the treatment of AD.

I believe there's more out there on the topic, but that's all I have time for now.

I think I'll try the Zantac on the theory that I am more in need of H2 blockade than avoiding a 1 point anticholinergic ("low risk of anticholinergic side effects").

[circular]

Enter ApoE4 specifically in the histamine topic:

Neurol Res. 2007 Apr;29(3):243-50.
Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway.
Mace BE1, Wang H, Lynch JR, Moss J, Sullivan P, Colton H, Morgan K, Renauld JC, Laskowitz DT.
Author information

Abstract
Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.

PMID: 17509222 [PubMed - indexed for MEDLINE]

[tesslo]

Thanks Richard, I cannot use Clonazepam or any other of that family of drug either, I actually get an allergic response to it. All the substrates on the list I have trouble with, I cannot take Melatonin! I have paradoxical effects with it....

Interesting because on my DNA testing it stated I was a slow metabolizer of Amitriptyline which I had be prescribed by my doctor for residual peripheral neuropathy after shingles. He prescribed 10mg and I had to reduce it to 5mg, it still worked well without feeling like I was hit by a truck in the morning...and I only took it as needed maybe a couple of times a month, pain usually triggered by stress. Slow metabolizer of caffeine also, maybe everything.

Tesslo - Very low doses of amitriptyline can be used for peripheral neuropathy - way lower than is used for its anti-depressant effect. You may be a generally slow metabolizer if you have liver problems, but I would first look at those substances metabolized by the P450 1A2 enzyme system. The liver has a variety of P450 enzymes of which the 1A2 is responsible both for caffeine and amitriptyline. If you want to read a bit more about the 1A2 system, try http://en.wikipedia.org/wiki/CYP1A2 which cites some substances that either promote or inhibit 1A2. Clonazepam is metabolized by P450 3A4.

[jenniferthequeen]

Hey everyone, and Happy Thanksgiving to those who celebrate it.

Question for the brain trust: If we are suffering with seasonal allergies, has a determination been made which is the safest of the "non-drowsy" antihistamines for us 4/4-ers to use?

All this "not global warming" warm weather we've been having in the mid-Atlantic states has been wreaking havoc with my sinuses....I am unsure which little pill might be safest.

Your advice is appreciated. - Jen


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[Julie G]

Waves, Jennifer! Somewhere buried in our treasure trove, Silver posted a chart of anticholingeric drugs with a risk rating based on strength. Based upon that info, I use 10mg of Zyrtec as needed.