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My primary care doctor is telling all of her patients not to take Zyrtec for an anti-histamine because it is causing dementia side effects in her older patients

My primary care doctor is telling all of her patients not to take Zyrtec for an anti-histamine because it is causing dementia side effects in her older patients. Antecdotal but interesting.

johnisgood 2y ago
For the reasons I mentioned, yes. :) But Zyrtec is second-generation. It shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects, so it should be OK. May still cause drowsiness, however.
- wildylion 2y ago
  What about desloratadine?
  - johnisgood 2y ago
    Desloratadine (Clarinex, Aerius) is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor. From Wikipedia: > At very high doses, it is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses. Thus, it is an anticholinergic only at very high doses, and it does not readily pass the BBB, therefore drowsiness is NOT likely (probably at very high doses only). At any rate, it does not affect the CNS at therapeutic doses, so memory / cognition issues, along with drowsiness are not an issue. FWIW "2% of Caucasians and 18% of people from African descent are desloratadine poor metabolizers.", meaning "In these people, the drug reaches threefold higher plasma concentrations at seven hours after intake, and it has a half-life of 89 hours (compared to a 27-hour half-life in normal metabolizers). Adverse effects were reported at similar rates in poor metabolizers, suggesting that it is not clinically relevant.".
    - throwaway2037 2y ago
      Is BBB == "blood-brain barrier"?
      - johnisgood 2y ago
        Yes.
    - TechDebtDevin 2y ago
      Do you know if there are any SNPs correlated with poor desloratadine metabolizers?
      - johnisgood 2y ago
        I do not think that there are any definitive single nucleotide polymorphisms (SNPs) currently known to be specifically correlated with poor desloratadine metabolism. I think perhaps the genetic variation in the enzymes involves in its metabolism like UGT2B10 and CYP2C8 may contribute to differences in metabolism. There is just no conclusive identification of specific SNPs that definitively determine poor metabolizer status. The precise genetic variants (if any) have not yet been definitively pinpointed. For all we know, the differences may be attributable to variations in study design, sample sizes, definition of what constitutes a "poor metabolizer", and genetic heterogeneity among populations. Some reported rates of poor metabolizers vary, some studies report around 7% overall and 20% in African descent individuals, while others suggest the figures I have mentioned. There was a somewhat recent randomized study in healthy Chinese subjects, and found no statistically significant association between the UGT2B10 or CYP2C8 genotypes. What is clear is that while genetic factors are likely involved and poor metabolizer phenotype exists for the drug, no single genetic marker has yet been found to predict poor metabolism of this drug, and there is a notable interethnic difference in desloratadine metabolism. TL;DR: Currently there is no definitive evidence linking specific SNPs to poor desloratadine metabolism, but genetic variation in enzymes like UGT2B10 and CYP2C8 is implicated, but further research is needed. I hope this answers your question, but the bottom line is that more research is needed. If you know something, let me know though!

My primary care doctor is telling all of her patients not to take Zyrtec for an anti-histamine because it is causing dementia side effects in her older patients. Antecdotal but interesting.

johnisgood 2y ago

For the reasons I mentioned, yes. :) But Zyrtec is second-generation. It shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects, so it should be OK. May still cause drowsiness, however.

wildylion 2y ago
What about desloratadine?
- johnisgood 2y ago
  Desloratadine (Clarinex, Aerius) is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor. From Wikipedia: > At very high doses, it is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses. Thus, it is an anticholinergic only at very high doses, and it does not readily pass the BBB, therefore drowsiness is NOT likely (probably at very high doses only). At any rate, it does not affect the CNS at therapeutic doses, so memory / cognition issues, along with drowsiness are not an issue. FWIW "2% of Caucasians and 18% of people from African descent are desloratadine poor metabolizers.", meaning "In these people, the drug reaches threefold higher plasma concentrations at seven hours after intake, and it has a half-life of 89 hours (compared to a 27-hour half-life in normal metabolizers). Adverse effects were reported at similar rates in poor metabolizers, suggesting that it is not clinically relevant.".
  - throwaway2037 2y ago
    Is BBB == "blood-brain barrier"?
    - johnisgood 2y ago
      Yes.
  - TechDebtDevin 2y ago
    Do you know if there are any SNPs correlated with poor desloratadine metabolizers?
    - johnisgood 2y ago
      I do not think that there are any definitive single nucleotide polymorphisms (SNPs) currently known to be specifically correlated with poor desloratadine metabolism. I think perhaps the genetic variation in the enzymes involves in its metabolism like UGT2B10 and CYP2C8 may contribute to differences in metabolism. There is just no conclusive identification of specific SNPs that definitively determine poor metabolizer status. The precise genetic variants (if any) have not yet been definitively pinpointed. For all we know, the differences may be attributable to variations in study design, sample sizes, definition of what constitutes a "poor metabolizer", and genetic heterogeneity among populations. Some reported rates of poor metabolizers vary, some studies report around 7% overall and 20% in African descent individuals, while others suggest the figures I have mentioned. There was a somewhat recent randomized study in healthy Chinese subjects, and found no statistically significant association between the UGT2B10 or CYP2C8 genotypes. What is clear is that while genetic factors are likely involved and poor metabolizer phenotype exists for the drug, no single genetic marker has yet been found to predict poor metabolism of this drug, and there is a notable interethnic difference in desloratadine metabolism. TL;DR: Currently there is no definitive evidence linking specific SNPs to poor desloratadine metabolism, but genetic variation in enzymes like UGT2B10 and CYP2C8 is implicated, but further research is needed. I hope this answers your question, but the bottom line is that more research is needed. If you know something, let me know though!