Acetylcholinesterase inhibitors side effects

A systematic search of published literature identified 13 studies concerned with the value for money of acetylcholinesterase inhibitors. The majority were cost analyses of the potential savings in providing health and social care which may accrue from the introduction of these drugs. However, the available clinical evidence is not sufficient to support the assumption that acetylcholinesterase inhibitors are equivalent to other interventions in terms of clinical effect or side effects (Birks and Melzer, 1999 NICE, 2001). Furthermore, research to assess potential cost savings implicitly assumes that... 

Donepezil is a piperidine cholinesterase inhibitor, which reversibly and non-competitively inhibits centrally active acetylcholinesterase 34 This specificity is claimed to result in fewer peripheral side effects as compared to the other ChE inhibitors. 

Donepezil is primarily a reversible inhibitor of acetylcholinesterase with a long elimination half-life. It lacks the hepatotoxicity of tacrine but frequently causes nausea, vomiting and diarrhoea. These side effects, together with occasional bradycardia, sycope and changes in the sleep architecture, are directly associated with a central and peripheral enhancement of cholinergic function. At the present time, donepezil is the most widely prescribed anticholinesterase in the United States and Europe. 

Galantamine, unlike the other anticholinesterases in clinical use, is derived from the alkaloids from the daffodil and snowdrop family. It is a reversible, competitive inhibitor of acetylcholinesterase with some inhibitory action on butyryl cholinesterase. It is also an agonist at nicotinic receptor sites. Although a clinically effective drug, galantamine frequently causes gastrointestinal side effects. 

A new strategy in drug discovery, the selective optimization of side activities (the SOSA approach), has been formulated by Camille Wermuth [17,18 cf. Chapter I—1], In this approach, minor side activities of active compounds serve as the starting point for structural variations, ultimately to obtain analogues that now have the former side effect as their main activity. In this manner, nanomolar acetylcholinesterase (AChE) inhibitors as well as nanomolar muscarinic M, receptor and 5-HT3 receptor ligands could be derived from the antidepressant minaprine [17,18],... 

Donepezil was the second cholinesterase inhibitor approved in the US [6]. It is currently the only acetylchohnesterase approved by the FDA for the treatment of severe Alzheimer s disease. Donepezil is a reversible, noncompetitive chohnesterase inhibitor. It has a high binding specificity for brain acetylcholinesterase, with httle to no affinity for butylchohnesterase. Compared with the other cholinesterase inhibitors in this class, donepezil may be better tolerated, with less gastrointestinal side effects. The long half-life of this medication allows once a day dosing (See Table 3). 

I Piperidine derivative, reversible chohnesterase inhibitor with high specificity for acetylcholinesterase over bntyiylcholinesterase (may reduce peripheral side-effects). I Long elimination half-life (70-80 honrs) allows once-daily dosage. 

There are no effective therapies for Alzheimer s disease and no cure. Treatment aims to enhance cholinergic transmission. The most useful drugs are central acetylcholinesterase inhibitors, for example donepezil. Acetylcholinesterase is the enzyme that normally breaks down acetylcholine after it has interacted with its receptors at the synapse. Inhibition of this enzyme in the brain increases the amount of acetylcholine available and prolongs its action. These drugs produce a modest improvement in memory or slow progression of symptoms in some patients. The response to anti-cholinesterase drugs may take several weeks. Their use is limited by side effects, which can be severe. 

Side effects of acetylcholinesterase inhibitors include abdominal cramps, nausea, vomiting and diarrhoea and liver damage. 

Topical miotic agents are historically important glaucoma medications but are less commonly used today. Miotics lower lOP by causing muscarinic-induced contraction of the ciliary muscle, which facilitates aqueous outflow. They do not affect aqueous production. Multiple miotic agents have been developed. Pilocarpine and carbachol are cholinomimetics that stimulate muscarinic receptors. Ecbotbiopbate (Phospholine iodide) is an organophosphate inhibitor of acetylcholinesterase it is relatively stable in aqueous solution and, by virtue of its quaternary ammonium structure, is positively charged and poorly absorbed. The usefulness of these medicines is lessened by their numerous side effects and the need to use them three to four times a day. 

Acetylcholinesterase inhibitors used for reversing the effects of nondepolarizing muscle relax-ants cause increases in ACh at all sites where it acts as a neurotransmitter. To offset the resulting side effects, including bradycardia, a muscarinic blocking agent is used concomitantly. The answer is (D). 

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