Therapie der Myasthenia gravis mit Cholinesterase-Hemmstoffen - Prinzipien und pharmakologisches Monitoring*

Abstract

Cholinesterase inhibitors are still important in the treatment of myasthenic patients. Therapeutic principles, indications and adverse effects are discussed in detail. Methods of pharmacological monitoring had been searched over many years. Besides determination of pyridostigmine plasma concentration, erythrocyte-bound acetylcholinesterase (AChE) activity could provide a possibility to monitor therapy with cholinesterase inhibitors. 88 patients with myasthenia gravis were investigated. The results demonstrated that after pyridostigmine erythrocyte-bound as well as synaptic AChE is inhibited. Moreover, erythrocyte-bound AChE has proven to be a parameter of cholinesterase inhibitor effect. After injection of edrophonium-chloride (Tensilon) inhibition of AChE activity can be demonstrated as well. During steady pyridostigmine doses stable plasma concentrations and AChE inhibition depend on the respective dosage. Higher daily doses result in greater stability of pharmacologic parameters, whereas low daily doses lead to great interindividual differences of AChE inhibition even after equal pyridostigmine doses. Intraindividually there is no strong correlation, too. Therefore estimation of erythrocyte-bound AChE activity is not useful for routine pharmacological monitoring of cholinesterase inhibitor therapy, but may be helpful in some clinical conditions. The method provides some advantages over pyridostigmine plasma concentration, since it is applicable for other cholinesterase inhibitors, too, and since it requires less technical equipment and time.

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review

“…17,18 Finally, a pharmacodynamic parameter that is sometimes used to monitor CIs is represented by red blood cell cholinesterase activity, especially when CIs are administered in patients with chronic diseases such as myasthenia gravis. [19][20][21][22] For example, a single oral dose of 5 mg of pyridostigmine inhibited red blood cell cholinesterase by about 15%, a result generally considered a safe level of inhibition. [23][24][25]…”

The pharmacological treatment of acute colonic pseudo‐obstruction

“…Red blood cell cholinesterase activity is a pharmacodynamic parameter that is sometimes monitored when administering cholinesterase inhibitors, especially when they are intended for chronic use (e.g. Alzheimer’s disease and myasthenia gravis) 41–44 . A 5‐mg single oral dose of pyridostigmine in dogs significantly increased colonic spike activity (Figure 3) and inhibited red blood cell cholinesterase by about 15%, which is generally considered to be a safe level of inhibition 45–47 .…”

Formulating a new basis for the treatment against botulinum neurotoxin intoxication: 3,4-Diaminopyridine prodrug design and characterization

“…The stigmines, a class of carbamate-based AChE inhibitors, provide effective treatment of multiple sclerosis, 16 myasthenia gravis, 17 and Alzheimer’s disease. 18 Mechanistically, carbamates produce reversible covalent inhibition via transesterification between the carbamoyl-moiety and the active site serine.…”