Cholinesterase Inhibitors PDF

10/24/23, 3:16 PM Realizeit for Student Cholinesterase Inhibitors: Reversible Indirect-Acting Cholinergics Donepezil (Aricept) is the prototype drug in this class. Treatment of Alzheimer’s disease is the primary use for this centrally acting reversible cholinesterase inhibitor. This drug interfere...

10/24/23, 3:16 PM Realizeit for Student Cholinesterase Inhibitors: Reversible Indirect-Acting Cholinergics Donepezil (Aricept) is the prototype drug in this class. Treatment of Alzheimer’s disease is the primary use for this centrally acting reversible cholinesterase inhibitor. This drug interferes with enzyme that allows for the production of acetylcholinesterase, thus increasing acetylcholine and improving memory. Pharmacokinetics Absorption of donepezil after oral administration is good, and it is unaffected by food. The drug is highly bound (96%) to plasma proteins. The peak of action occurs in 3 to 8 hours. Metabolism takes place in the liver, producing several metabolites, some of which are pharmacologically active. Excretion of these metabolites and some unchanged drug occurs mainly in urine. Action Donepezil increases acetylcholine in the brain by inhibiting its metabolism, leading to elevated acetylcholine levels in the cortex. This slows the neuronal degradation that occurs in Alzheimer’s disease. Use As previously stated, health care providers use donepezil to treat mild, moderate, or severe Alzheimer’s disease. Long-term studies have shown that the drug delays the progression of the disease for up to 55 weeks. Other uses include enhancing memory in other neurologic conditions such as multiple sclerosis, treating myasthenia gravis, or treating overdoses of atropine and centrally acting anticholinergic drugs (e.g., those used for parkinsonism). Table 47.3 presents dosage information for donepezil and related drugs. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 1/8 10/24/23, 3:16 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 2/8 10/24/23, 3:16 PM Realizeit for Student Use in Older Adults Older adults are more likely to experience adverse drug effects because of age-related physiologic changes and superimposed pathologic conditions. Use in Patients With Hepatic Impairment Liver disease may impair the hepatic metabolism of donepezil, resulting in increased adverse effects. It is important to monitor a patient's liver function and clinical response to the medication carefully. Use in Patients With Critical Illness Donepezil has several specific uses in critical illness, which include reducing cognitive dysfunction. Commonly, critically ill patients may have delirium, a form of acute cognitive dysfunction that manifests as a fluctuating change in mental status, with inattention and altered level of consciousness. As many as 80% of mechanically ventilated patients are in the intensive care unit; this makes donepezil an important management drug. Use in Patients Receiving Home Care https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 3/8 10/24/23, 3:16 PM Realizeit for Student Patients with Alzheimer's disease may have problems with remembering to take medications and may easily underdose or overdose themselves. It is important for the home care nurse to work with responsible family members in such cases to ensure accurate drug administration. Adverse Effects The most common adverse effects of donepezil are headache, dizziness, depression, vertigo, and insomnia. Possible drug-related GI conditions include nausea, vomiting, diarrhea, abdominal muscle cramps, anorexia, and GI bleeding. The most serious adverse effects are breathing problems (e.g., asthma, chronic obstructive pulmonary disease), fainting, and heart disease (e.g., sick sinus syndrome, other heart conduction disorder). Dyspnea has been reported and is more common in patients who have previous lung disease. In addition, fatigue and anorexia may occur. Other adverse effects include seizures and trouble urinating. Contraindications Contraindications to donepezil include known hypersensitivity to the drug. Patients with lung disease or heart disease such as sick sinus syndrome should not take this medication. Nursing Implications Preventing Interactions Many medications interact with donepezil, increasing or decreasing its effects (Box 47.3). BOX 47.3 Drug Interactions: Donepezil Drugs That Increase the Effects of Donepezil Theophylline Increases the risk of toxicity Cholinesterase inhibitors Increase the risk of toxicity Drugs That Decrease the Effects of Donepezil Anticholinergics Decrease the efficacy Nonsteroidal anti-inflammatory drugs Increase the risk of gastrointestinal bleeding Administering the Medication Before administering donepezil, the nurse assesses the patient for allergy, orientation, and contraindications. Administration should occur at bedtime each day. If the patient is taking an oral disintegrating tablet, the nurse ensures that the medication is dissolved on the tongue. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 4/8 10/24/23, 3:16 PM Realizeit for Student QSEN Alert: Safety The brand names for donepezil (Aricept) and rabeprazole (AcipHex) are a source of confusion. It is essential to use caution when administering either of these drugs. Assessing for Therapeutic Effects The nurse assesses for improved memory and reduction of dementia. This involves assessing daily for memory changes, forgetfulness, and mood. Assessing for Adverse Effects The nurse assesses for signs and symptoms of GI upset such as nausea, diarrhea, insomnia, and vomiting. If GI bleeding is suspected, it is important to obtain an order for laboratory tests such as complete blood count and bleeding time. Patient Teaching Box 47.4 identifies patient teaching guidelines for donepezil. BOX 47.4 Patient Teaching Guidelines for Cholinesterase Inhibitors: Donepezil Take this drug exactly as prescribed, at bedtime. Place orally disintegrating tablet on your tongue; allow it to dissolve and then drink water. Know that this drug does not cure the disease but is thought to slow down the degeneration associated with the disease. Continue taking this drug if no change in symptoms is noted. Arrange for regular blood tests and follow-up visits while adjusting to this drug. Note that the following side effects may occur: nausea, vomiting (eat frequent small meals), insomnia, fatigue, and confusion (use caution if driving or performing tasks that require alertness). Report severe nausea, vomiting, changes in stool or urine color, diarrhea, changes in neurologic functioning, and yellowing of the eyes or skin to your health care provider. Other Drugs in the Class Galantamine hydrobromide (Razadyne, Razadyne ER) is similar to donepezil in its action. Indications include mild to moderate dementia and vascular dementia (unlabeled use). Contraindications include severe hepatic or renal impairment. The most common adverse effects are insomnia, tremor, dizziness, somnolence, headache, bradycardia, and syncope. Patients and families should receive instructions about reporting any changes in mental status. To decrease gastric upset, it is necessary to take the medication with food. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 5/8 10/24/23, 3:16 PM Realizeit for Student Rivastigmine (Exelon, Exelon Patch) is a long-acting central cholinesterase inhibitor approved for the treatment of mild to moderate dementia due to Alzheimer’s disease as well as Parkinson’s disease. Like other drugs in this class, rivastigmine is not a cure for Alzheimer’s disease but does slow the progression of symptoms. Oral rivastigmine lasts 12 hours, making twice-a-day dosing possible. Rivastigmine transdermal is applied as a patch once a day. The site of the transdermal application should be rotated. The site used should not be used again for a period of 14 days. Before a new patch is applied, the old patch should be removed and the area cleaned. The patch should be applied to dry, clean skin. Metabolism occurs in the liver, and excretion takes place in the feces. The side effect profile of rivastigmine is similar to that of donepezil. To minimize certain adverse effects (e.g., nausea, vomiting, loss of appetite), it is typically necessary to increase dosages slowly until the therapeutic dosage is reached. Patients may take the drug with food to decrease GI distress. N-Methyl-d-Aspartate Receptor Antagonist Memantine (Namenda), the prototype N-methyl-d-aspartate (NMDA) receptor antagonist, was approved for use in 2003. The drug is administered to patients with moderate to severe Alzheimer's disease. Its neuroprotective action is different from that of the cholinesterase inhibitors. Pharmacokinetics Memantine is well absorbed orally, with 100% absorption in the GI tract. It is easily distributed and easily transported across the blood–brain barrier. The drug is 45% protein bound. Its peak of action occurs in 3 to 7 hours with the immediate-release formulation and in 9 to 12 hours with the extended-release formulation. It is partially metabolized by the liver, independent of the cytochrome P450 enzyme system. The terminal elimination half-life is 60 to 80 hours. Action Glutamate is an excitatory amino acid in the CNS and is known to contribute to origin and development of Alzheimer’s disease. In Alzheimer’s patients, overstimulation of the glutamate receptors occurs, leading to cell death. NMDA is a glutamate receptor in which memantine induces an antagonistic effect. When the NMDA receptors are overstimulated, magnesium is prevented from reentering and blocking the channel from closing. Thus, an influx of calcium results, and neuronal cell death subsequently occurs. Memantine has the ability to bind to the magnesium site to block the excitatory function by slowing intracellular calcium accumulation. This action prevents nerve damage but does not have an effect on glutamate. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 6/8 10/24/23, 3:16 PM Realizeit for Student Use Memantine is used to slow the progression of moderate to severe Alzheimer's disease. Contraindications Contraindications include any hypersensitivity reaction to memantine. Also, patients with renal failure should not take the drug. Nursing Implications Preventing Interactions Memantine interacts with carbonic anhydrase and alkalinizing agents, resulting in increased serum concentration of memantine. Also, trimethoprim may lead to memantine toxicity. Administering the Medication Memantine should be administered without regard to meals. The extended-release formulation should be swallowed whole; it should not be chewed. The capsule can be opened and sprinkled on applesauce, which must be consumed immediately. The liquid formulation should be squirted in the corner of the patient's mouth and should not be mixed with any other liquid. Assessing for Therapeutic Effects The nurse assesses for improved memory and reduction in dementia. He or she should also assess for changes in memory and mood. Assessing for Adverse Effects The nurse should assess the patient for changes in blood pressure. Hypertension occurs in 4% of patients who take memantine, and hypotension may result with the extended-release formulation. He or she should assess for CNS adverse effects such as dizziness, confusion, anxiety, fatigue, and hallucinations. In addition, he or she should assess for diarrhea, constipation, vomiting, abdominal pain, urinary incontinence, back pain, and cough. Finally, he or she should assess for signs and symptoms of a hypersensitivity reaction. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 7/8 10/24/23, 3:16 PM Realizeit for Student Patient Teaching Instruct the patient’s caregiver about the administration of memantine. Because of the CNS effects, the patient should be protected from falls related to dizziness. In the event the patient develops GI symptoms, urinary incontinence, back pain, or cough, the prescriber should be notified. In addition, the caregiver should be instructed about hypersensitivity reactions, including skin rash, dyspnea, or bronchospasm. Cholinesterase Inhibitor–N-Methyl-d-Aspartate Receptor Antagonist Donepezil and memantine are available as a combination of a cholinesterase inhibitor and an NMDA—as Namzaric. For the actions of this combination drug, see previous discussions. Donepezil–memantine is administered to patients with moderate to severe dementia. This oral agent is for patients who are stabilized on 10 mg donepezil once daily but are not taking memantine. Initial dose of memantine extended-release of 7 mg combined with donepezil 10 mg once daily. The dosage can be increased weekly with a maintenance dose of memantine extended-release of 28 mg and donepezil 10 mg daily. The nurse must assess for cardiovascular adverse effects. The donepezil may cause bradycardia and heart block. Patients should be protected from falls; there is a risk of syncopal episodes. Diarrhea, nausea, and vomiting may develop and commonly resolve in 1 to 3 weeks. As with other medications administered for Alzheimer’s disease, it is important to monitor the patient’s mental status and ability to perform activities of daily living. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2b… 8/8