Drug interactions AChE inhibitors

FIGURE 12-25. Icon for the cholinesterase inhibitor tacrine. This was the first cholinesterase inhibitor, but since it is a hepatoxotin, it has been relegated to second-line use. Also, it must be given four times daily, is difficult to dose, and has several drug interactions. It is short-acting, reversible, and nonselective, inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). 

In conclusion, we were able to design AChE inhibitors based on the docking and GRID/GOLPE study which seems to interact simultaneously with the cation-re subsite of the catalytic site and the peripheral site of the enzyme. Eurther support for our docking study came from the crystal structure of a novel Ach E-inhibitor complex [78]. The crystal structure of AChE complexed with the marketed drug donepezil was solved in 1999. Like donepezil, our most potent inhibitors contain a benzylpiperidine moiety which shows a similar position and orientation when compared with the published crystal structure. The comparison of both AchE-inhibitor complexes revealed that both kind of inhibitors adopt a comparable conformation in the narrow binding pocket [12]. As we predicted for our ami-... 

Drug interactions hyperkalemia enhances effects and vice versa displaces digoxin from tissue binding sites, enhancing toxicity may oppose effects of AChE inhibitors in myasthenia. 

A 51-year-old woman was admitted to hospital with a 4-day history of muscular aches and weakness. Among other drugs, she had been taking zidovudine, lamivudine, indinavir, and simvastatin for 2 years. Ritonavir 100 mg twice daily had been added to her usual regimen 2 weeks previously. The rhabdomyolysis was therefore attributed to an interaction between ritonavir and simvastatin. Another similar case has also been reported. See also (b) above and (e) below for interactions of ritonavir combined with other protease inhibitors. 

---