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Related Experiment Videos

Beta-blocker brain concentrations in man.

J M Cruickshank, G Neil-Dwyer

    European Journal of Clinical Pharmacology
    |January 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    Beta-blockers benefit subarachnoid hemorrhage (SAH) patients. Hydrophilic atenolol showed lower brain concentrations than lipophilic beta-blockers, potentially reducing central nervous system side effects.

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    Area of Science:

    • Pharmacology
    • Neuroscience
    • Clinical Medicine

    Background:

    • Subarachnoid hemorrhage (SAH) is a critical neurological condition.
    • Beta-blockade therapy has demonstrated therapeutic benefits for SAH patients.
    • Understanding drug distribution in the brain is crucial for optimizing SAH treatment.

    Purpose of the Study:

    • To compare the brain and cerebrospinal fluid (CSF) concentrations of hydrophilic atenolol versus lipophilic beta-blockers (propranolol, oxprenolol, metoprolol) in SAH patients.
    • To investigate the relationship between plasma, CSF, and brain tissue concentrations of these beta-blockers.
    • To explore the implications of differential drug distribution on central nervous system (CNS) side effects.

    Main Methods:

    • Patients undergoing surgery for SAH were administered chronic oral treatment with either atenolol or one of three lipophilic beta-blockers.

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  • Concentrations of beta-blockers were measured in plasma, CSF, and brain tissue.
  • Brain/plasma concentration ratios were calculated for each drug.

    • Main Results:

    • Brain concentrations of lipophilic beta-blockers (propranolol, oxprenolol, metoprolol) were significantly higher (10-20 times) than those of hydrophilic atenolol.
    • Brain/plasma concentration ratios indicated substantial brain penetration for lipophilic agents (26-50) but minimal penetration for atenolol (0.2).
    • CSF concentrations did not accurately reflect brain tissue concentrations for any of the studied beta-blockers.

    Conclusions:

    • The hydrophilic beta-blocker atenolol exhibits limited brain penetration compared to lipophilic agents in SAH patients.
    • This restricted brain distribution of atenolol may explain its lower incidence of CNS-related side effects.
    • Therapeutic strategies for SAH should consider the pharmacokinetic properties, specifically brain penetration, of beta-blockers.