Patients with severe renal impairment may require a dosage reduction. Adding sodium bicarbonate would alkalinize the urine and increase memantine levels, causing toxicity. It is not necessary to discontinue or decrease the dose of the memantine with mild or moderate renal impairment.
Discontinuing the memantine
Adding sodium bicarbonate to the patient’s drug regimen
Reducing the dose of memantine
Continuing the memantine as ordered
Cardiovascular effects of cholinesterase inhibitor drugs are uncommon but cause the most concern. Bradycardia and fainting can occur when cholinergic receptors in the heart are activated. Confusion and memory impairment are signs of the disease and are not side effects of the drug. Dizziness, headache, nausea, vomiting, and diarrhea are all expected adverse effects, and although uncomfortable, they do not present an increased risk to the patient.
Slowed heart rate and lightheadedness
Confusion and memory impairment
Nausea, vomiting, and diarrhea
Dizziness and headache
Memantine modulates the effects of glutamate, which is involved in calcium influx into neuronal cells. Memantine is used for patients with moderate to severe AD. Memantine does not prevent calcium from leaving cells; it only affects the influx of calcium. In studies, although the effects of memantine and donepezil appear to be synergistic or may confer independent benefits, they only demonstrate improvement in cognitive function and not a stop in disease progression.
“Memantine prevents calcium from leaving neurons, which improves their function.”
“Memantine modulates the effects of glutamate to alter calcium influx into neurons.”
“Memantine is indicated for patients with mild to moderate Alzheimer’s disease.”
“Memantine and donepezil combined may stop progression of Alzheimer’s disease.”
The rivastigmine transdermal patch needs to be changed daily. Sites used should not be reused for 14 days. Transdermal dosing provides lower, steady levels of the drug. Intensity of side effects is lower with the transdermal patch. The old patch must be removed prior to applying the new patch to prevent toxicity.
“We should remove the old patch before applying the new one.”
“Reduced side effects occur with the transdermal patch.”
“We only need to change the patch every 2 weeks.”
“Doses are lower but more steady with the transdermal patch.”
Cholinesterase inhibitors produce modest improvements in cognition, behavior, and function and may slightly delay disease progression; they do not have a major impact on delaying progression of the disease. Gastrointestinal symptoms are common side effects. Drugs that block cholinergic receptors, including antihistamines, can reduce therapeutic effects and should be avoided. Cholinesterase inhibitors do not affect neurons already damaged, but they do improve function in those not yet affected.
“This drug helps neurons that aren’t already damaged to function better.”
“Gastrointestinal symptoms are common with this medication.”
“People taking this drug should not take antihistamines.”
“This drug significantly slows the progression of the disease.”
Donepezil is given for mild, moderate, and severe AD, and dosing may be increased, although it must be titrated up slowly. For patients with moderate to severe AD who have taken 10 mg once daily for at least 3 months, the dose can be increased to 23 mg once daily. Donepezil is not given twice daily. Donepezil does not cause hepatotoxicity; hepatotoxicity occurs with tacrine, the first acetylcholinesterase (AChE) inhibitor, which now is rarely used. Dosing is increased after 3 months, not 1 year.
The patient must take the drug for longer than 1 year before the dose can be increased.
The increase in symptoms is the result of hepatotoxicity from the medication’s side effects.
The dose can be increased to twice daily dosing instead of once daily dosing.
The dose can be increased, because the patient has been taking the drug for longer than 3 months.
This patient is showing signs of the natural progression of AD. Behavior problems such as these occur in 70% to 90% of patients with AD as the disease progresses. There is no need to notify the provider to report these symptoms, because they are expected. The time from onset of symptoms to death usually is 4 to 8 years, but it may be as long as 20 years; this progression does not represent the final stages. Medications are not effective for preventing disease progression, and their effects on memory and cognition are modest, so requesting an increase in the drug dose would not help in this situation.
Notify the provider of this patient’s worsening symptoms.
Request an increase in the medication dose to treat the exacerbation in symptoms.
Prepare the patient’s spouse for impending death from Alzheimer’s disease.
Tell the spouse that this is an expected progression of the disease.
Alzheimer’s disease is a disease in which symptoms progress relentlessly from mild to moderate to severe. Medications have not been clearly effective and do not stop the disease progression, although they may slow loss of memory and cognition and prolong independent function. There is no indication that available drugs stop disease progression if begun early in the course of the disease. There is no clearly effective therapy for core symptoms, but associated symptoms such as incontinence and depression may be treated.
“Medications to treat Alzheimer’s disease are effective for treating core symptoms of the disease.”
“Drugs may be effective to stop the progression of the disease if they are initiated early in the disease.”
“Drugs to treat Alzheimer’s disease may slow the progression of memory loss.”
“Medications for Alzheimer’s disease are effective in reducing cognitive impairment.”
Advancing age and a positive family history are the only two known risk factors. Female gender is not a known risk; the increased incidence among females may be the result of women living longer than men. No definitive genetic tests are available. The presence of apoE2 seems to be protective.
Genetic testing can provide a definitive measure of the risk.
Patients with the apolipoprotein E2 gene (apoE2) are more likely to develop the disease.
Advancing age and family history are known risk factors.
Female gender is known to increase the risk.
Phenobarbital has a long half-life and may be given once daily at bedtime to help manage its sedative effects. The serum drug level is within the normal range of 15 to 40 mcg/mL, so the dose does not need to be adjusted. Increasing the dose and the frequency is not necessary since the drug levels are therapeutic and scheduling the drug to three times daily will compound the sedative effects. The sedative side effects do not increase over time.
“This side effect is expected and should decrease over time. You should avoid driving in the meantime.”
“The drug level is low and you may need a higher dose, but taking it three times daily will reduce the drowsiness.”
“Your lab work shows a higher than normal level of the drug and your provider will probably lower your dose.”
“I will contact your provider to discuss changing your dosing to once daily to minimize the drowsiness.”
Valproic acid is given initially at a dose of 5 to 15 mg/kg/day, administered in two divided doses. This child is receiving 400 mg/day, which is 10 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/day each week until optimal levels are achieved up to a maximum dose of 60 mg/kg/day. At this point, adding another AED or changing to another AED is not recommended. Increasing the dose to three times daily is not recommended.
Changing to phenytoin [Dilantin] since the valproic acid is not effective
Increasing the dose of valproic acid to 300 mg PO twice daily
Increasing the dose of valproic acid to 200 mg three times daily
Adding another seizure medication to supplement the valproic acid
Lamotrigine can cause life-threatening rashes, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, and this risk increases with concurrent use of valproic acid. Angioedema is an adverse effect associated with pregabalin. Hypohidrosis and psychosis are associated with topiramate.
Oxcarbazepine can cause clinically significant hyponatremia in 2.5% of patients. If oxcarbazepine is combined with other drugs that reduce sodium, the patient should be monitored. Signs of hyponatremia include nausea, drowsiness, confusion, and headache, and patients should be taught to report these symptoms. Increasing the dose of oxcarbazepine is not indicated. Rashes can indicate a serious drug reaction, and providers should be notified so that the oxcarbazepine can be withdrawn. Salt substitutes would compound the problem of hyponatremia.
“I may develop a rash and itching, but these are not considered serious.”
“I should report any nausea, drowsiness, and headache to my provider.”
“I may need to increase my dose of Trileptal while taking these medications.”
“I should use salt substitutes instead of real salt while taking these drugs.”
Valproic acid competes with phenobarbital for drug-metabolizing enzymes and can increase plasma levels of phenobarbital by approximately 40%. When this combination is used, the dose of phenobarbital should be reduced. Increasing the dose of valproic acid would compound the problem. Patients taking phenobarbital alone experience sedation, which diminishes as tolerance develops. Liver toxicity is a rare adverse effect of valproic acid and is marked by symptoms of nausea, vomiting, and malaise, not drowsiness.
Notify the prescriber of the need to increase the dose of valproic acid.
Explain to the patient that tolerance to sedation eventually will develop.
Request an order for liver function tests to monitor for hepatotoxicity.
Notify the prescriber, and request an order to reduce the dose of phenobarbital.
Measurements of plasma drug levels are less important than observation of seizure activity for determining effective dosages for absence seizures, because this type of seizure is characterized by as many as several hundred occurrences a day. Keeping a chart of seizure activity is the best way to monitor drug effectiveness when treating absence seizures. Frequent drug level monitoring is important when side effects occur to ensure that drug toxicity is not occurring. Learning about the disorder is an important part of adherence. Dizziness and drowsiness are common side effects that diminish with continued use.
reporting dizziness and drowsiness to the provider.
learning as much as possible about the disorder and its treatment.
frequent serum drug level monitoring.
recording the number of seizures the child has each day.
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