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Relationship between bronchial effects and plasma practolol concentration in man.

V M Oh, E A Taylor, J Wadsworth

European Journal of Clinical Pharmacology

|March 26, 1979

Summary

High doses of practolol may cause breathing difficulties in healthy volunteers, similar to propranolol. This suggests practolol loses its heart-selective effects at higher concentrations, potentially obstructing airflow.

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Area of Science:

Cardiology
Pharmacology
Respiratory Medicine

Background:

Beta-adrenoceptor antagonists, like practolol, are used for cardiovascular conditions.
Cardioselectivity is a key property, minimizing non-cardiac side effects.
Understanding dose-dependent effects on both cardiac and respiratory function is crucial.

Purpose of the Study:

To investigate the effects of single high versus low doses of practolol on heart rate and ventilation.
To compare practolol's effects with propranolol and placebo during rest and exercise.
To determine the plasma concentration threshold at which practolol may lose cardioselectivity.

Main Methods:

Double-blind, balanced, randomized study in 8 healthy volunteers.
Intravenous administration of practolol (1 and 4 mg/kg), propranolol (0.2 mg/kg), and placebo at weekly intervals.

Related Experiment Videos

Assessment of cardiac beta-blockade via exercise heart rate reduction and bronchial beta-blockade via peak expiratory flow rate (PEFR) changes.

Main Results:

All active treatments significantly reduced exercise heart rate, with practolol 4 mg/kg showing the greatest effect.
Propranolol and high-dose practolol significantly reduced PEFR compared to low-dose practolol and placebo.
Higher plasma concentrations of practolol (after 4 mg/kg dose) correlated with reduced PEFR.

Conclusions:

Practolol may lose its cardioselectivity and induce airflow obstruction at plasma concentrations above approximately 2 microgram/ml.
High doses of practolol can impair respiratory function, similar to non-selective beta-blockers.
Dose-dependent effects are critical for understanding the safety profile of beta-blockers.