Cholinesterase inhibitors adverse effects

A highly toxic substance by ingestion, and possibly by most other routes of exposure moderately toxic by inhalation and skin contact cholinesterase inhibitor toxic effects are similar to those of other carbamate pesticides and include excessive salivation, lacrimation, slow heart rate, blurred vision, twitching of muscle and lack of coordination, nausea, weakness, diarrhea and abdominal pain oral intake of probably 1.5-3 g could be fatal to adult humans a teratogenic substance, producing adverse reproductive effects in experimental animals. 

Tacrine is particularly damaging to the liver and can result in hepatotoxicity. Because tacrine is more likely to cause adverse reactions and drug interactions, it must be administered more frequently (4 times a day) and is rarely used in current therapy. Donepezil has fewer and milder side effects than tacrine It is considered the agent of first choice However, some patients may achieve a better response with one drug than another. Additional adverse reactions are listed in the Summary Drug Table Cholinesterase Inhibitors. 

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... 

Cardiovascular conditions - Cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. These actions may be particularly important to patients with supraventricular cardiac conduction disorders or to patients taking other drugs concomitantly that significantly slow heart rate. Consider all patients to be at risk for adverse effects on cardiac conduction. 

The cholinesterase inhibitors cause significant adverse effects, including nausea and vomiting, and other peripheral cholinomimetic effects. These drugs should be used with caution in patients receiving other drugs that inhibit cytochrome P450 enzymes (eg, ketoconazole, quinidine see Chapter 4). Preparations available are listed in Chapter 7. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Q7 What are the adverse effects associated with cholinesterase inhibitors ... 

Q7 The adverse effects associated with cholinesterase inhibitors are related to excessive cholinergic stimulation. These include gastrointestinal disturbances such as abdominal cramps and nausea, salivation, sweating, flushing, bron-choconstriction and urinary incontinence. 

Dichlorvos is a known inhibitor of cholinesterase, and it is likely that under certain conditions of use, a significant degree of inhibition might occur. However, under the conditions of these experiments, no such effect appears to have occurred. The subjects indicated no adverse effects. 

Overall, memantine has been well tolerated in clinical trials. The most frequent adverse events associated with memantine include constipation, confusion, dizziness, headache, coughing, and hypertension. As some of these side effects are also reported with cholinesterase inhibitors, caution should be used when administering memantine with this class of medications. ... 

Carbachol is a potent direct-acting miotic agent its duration of action is longer than that of pilocarpine (8 to 10 hours) because of resistance to hydrolysis by cholinesterases. This drug also may act as a weak inhibitor of cholinesterase. Patients with an inadequate response to or intolerance of pilocarpine as a result of ocular hritation or allergy frequently do well on carbachol. The ocular and systemic adverse effects of carbachol are similar to butmore frequent, constant, and severe than those of pilocarpine. " ... 

Use of NLO likely improves response and reduces systemic adverse effects and should be performed by all patients administering cholinesterase inhibitors. These agents should be used with caution in patients with asthma, retinal detachments, narrow angles, bradycardia, hypotension, heart failure, Down s syndrome, epilepsy, parkinsonism, peptic ulcer, and ocular inflammation, as well as in those receiving cholinesterase inhibitor therapy for myasthenia gravis or exposure to carbamate or organophosphate insecticides and pesticides. ... 

Edrophonium has the same adverse (cholinergic) effects as other cholinesterase inhibitors. However, the short duration of the drug does not allow for manifestation of these effects. Thus, observed adverse effects are negligible. 

A. Some adverse effects include dry mouth, blurred vision, cycloplegia, mydriasis, palpitations, tachycardia, aggravation of angina, and constipation. Urinary retention is common, and a Foley catheter may be needed. Duration of effects may be prolonged (several hours). Additionally, CNS anticholinergic toxicity (delirium) may occur with large doses of atropine needed to treat cholinesterase inhibitor poisoning. 

Carbaryl (1-naphthyl Af-methylcarbamate, Sevin [CAS 63-25-2]) A carbamate-type cholinesterase inhibitor (see p 291). Evidence of adverse effects on fetal development in test animals at high doses. 5 mg/m 100 mg/m Coloriess, white or gray solid. Odoriess. Vapor pressure is 0.005 mm Hg at 20°C (68°F). Breakdown products Include oxides ot nitrogen and methyl-amine. 

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