The anticholinesterase drugs (or cholinesterase inhibitors) can be classified as centrally-acting, reversible inhibitors such as donepezil (used in treatment of Alzheimer’s disease), reversible inhibitors with poor CNS penetration, such as neostigmine (used in treatment of myasthenia gravis), or irreversible inhibitors, such as ecothiopate and metrifonate. The centrally-acting anticholinesterases and reversible anticholinesterases form basis of this section, and these are listed in table 1 below,(see below). Interactions where anticholinesterases are affecting other drugs are covered elsewhere in publication.
Due to their differing pharmacokinetic characteristics, centrally-acting anticholinesterases have slightly different interaction profiles, although they share a number of common pharmacodynamic interactions. Tacrine(See reference number 1) is metabolised by cytochrome P450 isoenzyme CYP1A2, and so interacts with fluvoxamine, , a potent inhibitor of this isoenzyme, whereas there is no evidence to suggest other centrally acting anticholinesterases do. On other hand, donepezil(See reference number 1) and galantamine(See reference number 1) are metabolised by cytochrome P450 isoenzymes CYP3A4 and CYP2D6, and so they may interact with ketoconazole, and quinidine, , respectively, whereas tacrine would not be expected to do so. Rivastigmine,(See reference number 1) which is metabolised by conjugation,seems relatively free of pharmacokinetic interactions. Consideration of concurrent drug use would therefore seem to be an important factor in choice of centrally-acting anticholinesterase.
Note that,organophosphorus compounds such as insecticides are also anticholinesterases.
1. Jann MW,Shirley KL, Small GW. Clinical pharmacokinetics and pharmacodynamics ofcholinesterase inhibitors. Clin Pharmacokinet (2002) 719–39.
6. McSwain ML,Forman LM. Severe parkinsonian symptom development on combination treat-Anticholinesterases; Centrally acting + ment with tacrine and haloperidol. J Clin Psychopharmacol (1995) 15, 284.
7. Maany I. Adverse interaction of tacrine and haloperidol. Am J Psychiatry (1996) 153,1504.
| Table 1 Anticholinesterase drugs; reversible | |
|---|---|
| Centrally-acting inhibitors used principally for Alzheimer’s disease | Inhibitors with poor CNS penetration used principally for myasthenia gravis |
| Donepezil | Ambenonium |
| Galantamine | Distigmine |
| Rivastigmine | Edrophonium (mainly used diagnostically) |
| Tacrine | Neostigmine |
| Physostigmine | |
| Pyridostigmine (also used for glaucoma) | |