Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate

Abstract

Several specific and sensitive new methods for determining atropine and its metabolites in biological fluids have increased the possibility to characterise the pharmacokinetic properties of this antimuscarinic agent. Following i.v. injection, atropine disappears very quickly from the circulation, resembling its fast onset of action. Age, but not sex, appears to have a clear effect on its kinetics, explaining at least partly the higher sensitivity of very young and very old patients to this anticholinergic agent. Following i.m. or oral atropine administration, typical anticholinergic effects coincide quite well with the absorption rate of the drug, indicating that the premedication should be given about 1 and 2 h before induction of anaesthesia. A sufficient absorption after rectal administration offers an alternative treatment, especially in children. Differing from its placental transfer, atropine has a delayed and incomplete lumbar cerebrospinal fluid penetration, indicating a fundamental difference between these two biological membranes. Oropharyngeally administered atropine has a very variable absorption, but inhaled or intratracheally given drug has produced interesting new results, e.g. pulmonary atropine administration appears to have clinical significance in special situations, such as cardiac arrest and organophosphate poisoning (military personnel). Depending on the method used, different data on the metabolism and excretion for atropine have been reported and therefore further studies are needed in this respect. The pharmacokinetics of scopolamine and glycopyrrolate and their relation to clinical response are poorly understood.

Bronchoalveolar lavage in children

“…Many centres use also atropine [11,12] as premedication because it minimizes vasovagally-induced bradycardia and decreases airway secretion. Adults pretreated with atropine [13] have a higher BAL return than untreated control subjects but this has not been formally assessed in children.…”

The effect of ciclotropium on human heart rate

“…administration of ciclotropium causes a marked increase in heart rate in healthy young men [6] which is similar to the effect of atropine [4,16,17]. The rapid onset and the long duration of the effect of ciclotropium, compared to atropine, make it a potentially useful tool in the therapy of bradycardia [6].…”

“…before or after abdominal surgery. However, atropine therapy presents problems in such patients due to large interindividual clearance variations [17]. Thus, additional pharmacokinetic/dynamic studies in elderly patients comparing the effects of atropine and ciclotropium will be needed before ciclotropium can be recommended for treatment of bradycardia.…”

Plazentapassage von Anästhetika und Adjuvanzien

“…Die Belladonna-Alkaloide Atropin und Scopolamin [29] passieren schnell die plazentare Barriere und führen sowohl bei der Mutter als auch beim intrauterinen Feten simultan zur Herzfrequenzsteigerung [33]. Atropin kann bei strenger Indikationsstellung in klinisch übli-chen Dosierungen ohne Gefahr für den Feten eingesetzt werden.…”