investigations of respiratory effects have been short term. The opposing effects of PB administration in myasthenics complicate respiratory studies in this population. For example, Ringqvist and Ringqvist (1971) studied respiratory effects of intravenous or intramuscular PB in 10 moderate to severe myasthenics aged 17–64 years. They found an increase in airway resistance (Re) and in maximum inspiratory (PEmax) or expiratory pressure (Pimax) in all subjects within 60 minutes of drug administration, but also observed an increase in vital capacity (VC). All of the subjects reported subjective improvement in respiration with PB administration. Pulmonary function parameters rapidly returned to normal with administration of a sympathomimetic drug.

In another study of 21 myasthenics, Shale and coworkers (1983) observed a decrease in airflow (FEV%) and an increase in airway resistance at 90 to 120 minutes following a dose of 60 or 120 mg PB given orally. The effect was completely blocked when ipratropium (a muscarinic blocker) was given simultaneously with PB. In a post hoc analysis, the increased airway resistance was found to be present only in subjects with airflow obstruction present at baseline.

De Troyer and Borenstein (1980) administered PB to myasthenics and normal controls and followed pulmonary function for 1–2 hours after drug administration. The control subjects (n = 4) were males aged 29–37 years. Following a 2-mg intramuscular dose there was no change in static lung volumes, conductance, or flow–volume curves. The PB dose was not titrated and there was no measurement of ChE level following administration.

A clinical study of 12 normal and 13 asthmatic subjects by Ram and colleagues (1991) measured pulmonary function for 24 hours after PB administration. The subjects were all male nonsmokers. Normal and asthmatic subjects received 60 and 30 mg of oral PB, respectively. The mean decrease in ChE activity was 28.2 percent in normals and 23.3 percent in asthmatics. A small decrease in FEV1,6 but not FEV% or PEF (peak expiratory flow), was observed following PB at rest and postexertion in the normal subjects. The decrease correlated with ChE depression and was statistically, but not clinically, significant. Among the asthmatic subjects there was an exercise-induced increase in airway resistance, but no effect of PB at rest or with exercise.

In summary, the literature on respiratory effects of PB is sparse and inconsistent. Taken together, the existing studies suggest that mild increases in airflow obstruction may occur within 1–2 hours of PB administration, but the effects are subclinical and rapidly reversible. Asthmatics may experience a small increase in exercise-induced airway resistance following PB administration.

Healthy-Volunteer Studies

A number of studies were conducted in healthy military and nonmilitary volunteers to evaluate the tolerance of prophylactic doses of PB that might be

6  

FEV1 (forced expiratory volume) is the volume of gas expelled from the lungs during the first second of expiration after maximal inspiration.



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