Nausea donepezil

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Adverse reactions with donepezil include nausea, vomiting, and diarrhea. These are typical cholinergic side effects to expect with all of the cholinesterase inhibitors. Table 32-6 compares the major side effects for all of the approved agents for Alzheimer s disease.34-38... 

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. 

Further evidence that donepezil is effective and well tolerated in treating symptoms of mild to moderately severe Alzheimer s disease has emerged from a multinational trial (26). Common adverse effects were nausea, vomiting, diarrhea, anorexia, dizziness, and confusion, consistent with previous findings. 

A 79-year-old nursing home patient was given donepezil 50 mg in error. She developed nausea, vomiting, and persistent bradycardia—typical cholinergic adverse effects. She was treated with atropine, 0.2 mg as needed, for bradycardia (total dose 3 mg over 18 hours) and was discharged on the second day. 

A 74-year-old woman with a history of stroke, myocardial infarction, hypothyroidism, and probable multiinfarct dementia took nine donepezil tablets (a total dose of 45 mg). She developed nausea and vomiting 2 hours later. She fell asleep for 4-5 hours but remained rousable. About 9 hours after ingestion, she became flushed and had a bout of diarrhea. Donepezil was withdrawn for 3 days, and there were no adverse effects when it was reintroduced. 

Rivastigmine (1) was the second drug after donepezil in a class of second-generation acetylcholinesterase inhibitors to become commercially available. It is now marketed in over 60 countries worldwide, including those in Europe and South America and the United Kingdom. It has central selectivity, suggesting fewer peripheral adverse effects. These include nausea, vomiting, abdominal pain, and anorexia (2,3). Daily doses up to 12 mg were tolerated and produced improvement in patients with Alzheimer s disease (4). 

Adverse effects inevitably include cholinergic symptoms with nausea, diarrhoea and abdominal cramps appearing commonly. There may also be bradycardia, sinoatrial or atrioventricular block. Urinary incontinence, syncope, convulsions, and psychiatric disturbances also occur. Rapid dose increase appears to make symptoms more pronounced. Hepatotoxicity is a rare association with donepezil. 

Of the acetylcholinesterase inhibitors, tacrine, methoxy-tacrine, metrifonate, donepezil hydrochloride, and rivastigmine are used in the treatment of Alzheimer s disease. In 12-30% of patients with Alzheimer s disease, tacrine causes an increase in hepatic transaminase activity. Abdominal adverse effects are very frequent, for example nausea, anorexia, diarrhea. The peripheral cholinomimetic effects of tacrine occur in a very high proportion of patients, probably the majority. The hepatic effects seem to be such that the use of these new (and in some cases still experimental) drugs would not be justified in... 

I Donepezil. DonepeziF is a piperidine cholinesterase inhibitor with specificity for inhibition of acetylcholinesterase as compared to butyrylcholinesterase. This specificity is claimed to result in fewer peripheral side effects (such as nausea, vomiting, and diarrhea) than with nonspecific cholinesterase inhibitors such as tacrine. ... 

Donepezil should be initiated at a 5-mg/day dose in the morning and titrated to 10 mg/day after 4 to 6 weeks if it is well tolerated. Table 63-6 summarizes cholinesterase inhibitor dosing recommendations. The most common donepezil side effects are nausea, vomiting. 

After two weeks, Mr Jones s family is concerned that he does not seem to be any better. They also tell you that since starting on the donepezil, Mr Jones has been suffering from nausea and they wonder if this can be a side effect of the drug. 

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