Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

Abstract

The pharmacokinetics and some pharmacodynamic properties of atropine, glycopyrrolate and scopolamine are reviewed. With the development of new analytical methods for drug determination, it is now possible to measure relatively low concentrations of these drugs in biological fluids and, consequently, some new kinetic data have been collected. Following intravenous administration, a fast disappearance from the circulation is observed and due to a high total clearance value their elimination phase half-lives vary from 1 to 4 h. All these agents are nonselective muscarinic receptor antagonists, but their actions on various organ systems with cholinergic innervation show considerable diversity. The cardiovascular effects are of short duration; other peripheral muscarinic effects and CNS effects can last up to 8 h or even longer. Differing from atropine and scopolamine, glycopyrrolate as a quaternary amine penetrates the biological membranes (blood-CNS, placental barriers) slowly and incompletely, making it the drug of choice for elderly patients with coexisting diseases and for obstetric use. Similarly, its oral absorption is slow and erratic, and hence it cannot be used as an oral premedicant. Atropine, scopolamine and glycopyrrolate have a definitely faster absorption rate, when injected into the deltoid muscle compared with administration into the gluteal or vastus lateralis muscles. There appear to be significant differences in the metabolism and renal excretion of these agents. Scopolamine is apparently excreted into the urine mainly as inactive metabolites, nearly half of the atropine dose administered is recovered in the urine as the parent drug or as active metabolites and about 80% of glycopyrrolate is excreted as unchanged drug or active metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

“…Although intravenous administration of atropine offers the fastest route of absorption (Aaltonen et al, 1984;Ali-Melkkilä et al, 1993) and probably the most efficient line of treatment in OP poisoning, this novel respiratory formulation has been developed mainly for prophylactic local action in the lungs and as an alternate for delivering therapeutic amount of the antidote quickly in a pre-hospital set-up or in ambulances for mass treatment of casualties, where giving an intravenous injection may not be always possible due to non-availability of a paramedic and other logistical reasons. It is also worth mentioning here that although inhalation through dry powder inhalation (DPI) technology may be more suitable for emergency field use than nebulization, stability of submicronic DPI formulations is still an unresolved issue.…”

“…However, the peak plasma concentration (6-8 ng/mL) after giving a standard dose of 2 mg AS intramuscular injection does not occur until 30 min have elapsed, limiting its use as a therapeutic option, more so in case of mass casualty (Kehe et al, 1992;Ali et al, 2009). In a hospital setting, assuming the patient can be transported there, the intravenous bolus route is the fastest way to introduce and maintain a state of atropinization, with the peak pharmacological concentration occurring within 5-10 min (Berghem et al, 1980;Ali-Melkkilä et al, 1993;Ali et al, 2009). However, in the field conditions or in a pre-hospital setting where giving an intravenous injection may not be always possible, efforts are required to develop and evaluate alternative but effective routes so as to obtain therapeutic range and peak concentration of the drug in blood earlier than 30 min and as close to intravenous range as possible (Albuquerque et al, 2006).…”

Unexpected anterograde amnesia associated with Buscopan used as a predmedication for endocscopy

“…The onset of action of intramuscular hyoscine is from three to five minutes and the duration of spasmolytic and antisecretory action is fifteen minutes and several hours, respectively. Unlike hydrobromide, hyoscine butylbromide does not cross the blood-brain barrier and is rarely associated with central symptoms [2,3] . Although intramuscular hyoscine butylbromide is considered a safe drug, it is not without side effects.…”

Tropane alkaloids (from Datura sp.) as undesirable substances in animal feed - Scientific Opinion of the Panel on Contaminants in the Food Chain

“…However, as tropane alkaloids are readily absorbed through the skin and through mucous membranes (Lewis and Elvin-Lewis, 1977), a relatively high oral bioavailability may be assumed and data from intravenous/parenteral injections may provide a reliable indication of the fate of atropine after oral ingestion. In contrast to atropine, scopolamine has a limited oral bioavailability ranging from 10 to 50% (Putcha et al, 1991;Ali-Melkkilä, 1993). Following absorption, both alkaloids have a high volume of distribution (EMEA, 1997(EMEA, , 1998).…”