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    1. Lauring, A. S., Tenforde, M. W., Chappell, J. D., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., … Self, W. H. (2022). Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: Prospective observational study. BMJ, 376, e069761. https://doi.org/10.1136/bmj-2021-069761

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    1. Andreano, E., Paciello, I., Piccini, G., Manganaro, N., Pileri, P., Hyseni, I., Leonardi, M., Pantano, E., Abbiento, V., Benincasa, L., Giglioli, G., De Santi, C., Fabbiani, M., Rancan, I., Tumbarello, M., Montagnani, F., Sala, C., Montomoli, E., & Rappuoli, R. (2021). Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants. Nature, 1–7. https://doi.org/10.1038/s41586-021-04117-7

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    1. Twohig, K. A., Nyberg, T., Zaidi, A., Thelwall, S., Sinnathamby, M. A., Aliabadi, S., Seaman, S. R., Harris, R. J., Hope, R., Lopez-Bernal, J., Gallagher, E., Charlett, A., Angelis, D. D., Presanis, A. M., Dabrera, G., Koshy, C., Ash, A., Wise, E., Moore, N., … Gunson, R. (2021). Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: A cohort study. The Lancet Infectious Diseases, 0(0). https://doi.org/10.1016/S1473-3099(21)00475-8

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    1. CONCLUSIONS: These findings suggest that higher standing BP is a biomarker that helps identify persons with combat PTSD who are likely to benefit from prazosin. These results also are consistent with α1AR activation contributing to PTSD pathophysiology in a subgroup of patients.

      This is precisely the results I would expect. However, I completely disagree with their interpretation.

      People with high blood pressure (BP) can tolerate a reduction in BP without instigating compensatory mechanisms. People with normal or low BP would invoke compensation by the sympathetic nervous system in response to alpha blockade. This would counteract the depressant effects of adrenergic antagonism. Indeed, adrenaline and noradrenaline elevate in response to standing, which I find to be an obvious prediction. Thus, the lack of benefit from prazosin in these subjects may be mediated by an increase in adrenergic receptor activation other than the apha1-adrenoreceptor; in particular, the beta-adrenergic receptors are likely at fault. Propranolol, a beta-blocker, is used for PTSD, so this mechanism seems well substantiated.

      The study apparently found benefit for patients with BP over 110 (with more benefit for higher BP). Thus, I would conclude that systolic pressure below 110 induce compensation.

    1. Dizziness or lightheadedness may be more likely to occur in the elderly, who are more sensitive to the effects of phenoxybenzamine. In addition, phenoxybenzamine may reduce tolerance to cold temperatures in elderly patients.

      Increased sensitivity to cold by phenoxybenzamine could be the result of heat dissipation via peripheral vasodilation.

    1. Typical half-lives are greater than 20 hr, a turnover that is slower than that of several other classes of neurotransmitter and hormone receptors (9, 10, 12, 16).

      This is rather fast. It means that tolerance and withdrawal should develop relatively rapidly. This is consistent with the "first dose effects" observed with alpha blockers.

    1. Prazosin had no analgesic effect alone but dose-dependently potentiated morphine analgesia in morphine-naive mice. Another alpha(1)-adrenoceptor antagonist, corynanthine, had similar effects. Prazosin also increased the analgesic potency of the morphine test dose in morphine-tolerant mice. Naloxone-precipitated vertical jumping was not affected, but weight loss was reduced by prazosin. Acutely administered clonidine potentiated morphine analgesia and alleviated opioid withdrawal signs, as expected. We conclude that in addition to the already established involvement of alpha(2)-adrenoceptors in opioid actions, also alpha(1)-adrenoceptors have significant modulatory role in opioid analgesia and withdrawal.

      This is interesting but not exactly surprising, given that both are depressants. What is surprising, however, is the contrast between this and the fact that stimulants also enhance morphine analgesia.

      Potentiation of Opioid Analgesia by Psychostimulant Drugs: A Review00084-0/fulltext)