Alzheimer's

Question 1

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Question 2

Before a patient progresses to dementia, they may experience Mild Cognitive Impairment (MCI):

• MCI is different from normal aging because the impairments are measurable on screening tools for dementia. (Such as the Mini Mental State exam (MMSE) or the Montreal Cognitive Assessment (MoCA).
• “Measurable cognitive impairment”
• Preserved level of function

Answer 2

• ## allow these impairments are measurable, they do NOT impact an individual’s daily functioning.

Question 3

Mild Cognitive Impairment (MCI) vs. Dementia

Mild Cognitive Impairment
- measurable cognitive impairment
- preserved level of function
-

Answer 3

Dementia
-dementia interferes with an individual’s day to day functioning
- significant cognitive impairment
- interferes with independence

• patients with dementia require assistance with there activities of daily living. (e.g. such as paying bills, managing medications). This limits there ability to be independent.

Question 4

The most noticeable symptom initially with dementia is __________.

With dementia, the decline is more severe. Intellectual and social abilities progressively worsen, and functioning becomes impaired.

Answer 4

memory loss

Question 5

• -memory loss (often the first sign, noticed by a patient or caregiver), this could be short term memory loss, or the loss of memories of thigs that happened a long time ago.
• -difficulty planning and organizing
  (patients may forget details and next steps in a process and therefore have difficulty planning a meal or organizing items in their own home)
• -getting lost in familiar places
• • Difficulty finding words for common objects
• • Repeating words of information
• • Inability to learn or remember new information (have difficulty learning a new thing, or when to take new medications)
    ———————————————————————————————————–(As Dementia progresses, they develop signs that greatly impact there personality.)
• apathy and social disengagement (can be due to embarrassment or an attempt to hide condition).
• delusions and agitation (these are challenging symptoms for caregivers to handle, since can sometimes escalate to inappropriate behavior and aggression).
• poor coordination and motor function (movement disorders may develop which puts patients at risk of falling and further limits their independence).

Answer 5

• often times, patients with dementia, do not identify their own signs of cognitive impairment.
• when considering the diagnosis of dementia, the presence and input of a family member or caregiver is essential.
• Not all patients develop all these signs. Patients with different types of dementia, present with different patterns of signs and symptoms. And the type of dementia maybe differentiated from which symptoms a patient presents with first and which appear as the disease progresses.

Question 6

Dementia Types:
1)
2)
3)
4)

“It is possible for a patient to have multiple types of dementia”

Answer 6

1) Vascular
- often coincides with other types
- occurs when the blood vessels of the brain are damaged from chronic conditions (e.g. diabetes, hypertension, dyslipidemia)

2) Alzheimer’s
- 60-80% of cases
- Age > 65 years old

3) Lewy body

4) Frontotemporal

Question 7

The drugs used for Alzheimer’s disease, have been studied in the various types of dementia, but have not shown a great benefit.

Despite that, they are sometimes used in other dementia types in an attempt to reverse any amount of cognitive decline, even if small.

Question 8

Alzheimer’s Disease Pathophysiology:

• There are 3 important components to the disease

1)
2)
3)

Answer 8

1) Amyloid beta plaques
- first is the accumulation of extracellular amyloid beta plaques, this accumulation is sometimes attributed to genetic mutations which can cause increased production or decreased clearance of amyloid beta. Overall, we are not sure why these plaques develop.

2) Tau tangles
-second is the hyperphosphorylation of Tau proteins, which leads to intracellular tau tangles.

• both amyloid beta plaques and tau tangles are toxic to neurons. But Tau tangles in particular maybe responsible for the spread of Alzheimer’s disease throughout the brain.

3) Decreased acetylcholine
- amyloid beta plaques and tau tangles are toxic to neurons and therefore cause a loss of cholinergic neurons, which produce acetylcholine.
- lower levels of acetylcholine throughout the brain cause a decline in memory, attention, and other cognitive processes. This pathophysiological process is targeted by acetylcholinesterase inhibitors.

Question 9

Treatment Overview for Alzheimer’s disease:

(Non-drug interventions)
- Lifestyle modifications - should be applied to all patients with dementia, not those only with Alzheimer’s disease.

-

Answer 9

• Usually, some component of vascular dementia is present regardless of the type of dementia the patient has. This contributes to their symptoms.

-1) [Controlling blood glucose, blood pressure, cholesterol] - may prevent vascular dementia from getting worse and contributing to progressive decline.

-2) Exercise

-3) Eating a healthy diet
[Having scheduled exercise and regular meals encourage a consistent daily schedule which is often comforting for patients with memory loss.]

-4) Use Cognitive Rehabilitation: is a program that incorporates a group of treatments to help patients in early stages of dementia. Won’t reverse the progression of the disease. Cognitive rehabilitation can help maintain memory, as well as patients develop strategies to compensate for future decline. (e.g. problem-solving games, learning to use a daily planner, setting reminders or alarms on a smart phone to help remember tasks or events.)

-5) Socialize: Keeps patients with dementia engaged with the world around them, decreases depression, and maintains a support system.

Question 10

Treatment Overview for Alzheimer’s disease:

(Non-drug interventions)
- Natual Products:

What are the 2 commonly used supplements to improve memory?
1)
2)

Answer 10

• are a non-prescription drug option to address dementia
• Supplements purported to boost memory or treat dementia SHARE the same concerns as other supplements:

*[ Lack data to support efficacy, safety, purity]

1) Vitamin E
2) Ginkgo biloba

• not routinely recommended

Question 11

Treatment Overview for Alzheimer’s disease:

Drug Interventions:

• Unfortunately, drug treatment for Alzheimer’s disease does not offer a Cure or reversal of dementia that is already present.
• if used they should be expected to have only a modest effect on slowing cognitive decline. (This can be helpful because it may allow the patients to dress themselves independently or participate in social activities for a little while longer).
• The choice of drug treatment is determined by the severity of the patients dementia (the severity of cognitive function). Based on the score a patient achieves on the MMSE or MoCA screening tools.

What is MMSE?
What is MoCA?

Answer 11

Mini-Mental State Exam:
- Max score is 30
- a score less than < 24 indicates a memory disorder

Question 12

Treatment Overview for Alzheimer’s disease:

Drug Interventions:

There are 2 classes of drugs established to manage Alzheimer’s disease, which are?
1)
2)

Answer 12

1) Acetylcholinesterase inhibitors

2) NMDA blocker

Question 13

Treatment Overview for Alzheimer’s disease:

Drug Interventions: Acetylcholinesterase inhibitors

• the drugs in this class include: _______

Answer 13

• the primary treatment for Alzheimer’s disease
• donepezil, rivastigmine, galantamine
• they can be used in ALL stages of Alzheimer’s disease (Mild 18-26, Moderate 10-17, Severe 0-9)

Question 14

Treatment Overview for Alzheimer’s disease:

Drug Interventions: NMDA blockers

• the drugs in this class include: _________

Answer 14

• memantine (Namenda)
• ## is only used in Moderate-Severe disease, has not shown to provide benefit in patients with mild disease.

Question 15

What acetylcholinesterase inhibitors are used for Alzheimer’s dementia and other forms of dementia?

remember- “Patients with dementia DRAG along in life”

D-
R-
And
G-

*ARE these all the available treatments? No, there is one drug in its own class reserved for *Moderate to severe disease.

Answer 15

donepezil (Aricept) ARE
rivastigmine (Exelon)
galantamine (Razadyne, Razadyne ER)

memantine (Namenda)

Question 16

Amyloid Beta-Directed Antibodies:

• this is a new class of drugs that address the underlying pathophysiology of the disease
• What drugs are in this class?

Answer 16

• they have been shown to decrease the concentration of amyloid Beta, which is the protein that accumulates in patients with Alzheimer’s disease that results in the death of neurons.

[aducanumab, lecanemab]- (these are IV therapies that are infused every 2 or 4 weeks)
- These are FDA approved for only Mild Cognitive Impairment or mild dementia. Specifically due to the accumulation of amyloid Beta. Amyloid Beta concentrations must be measured prior to starting therapy. By using an MRI or cerebrospinal fluid test.

• although they address the underlying pathophysiology of Alzheimer’s disease. Overall, they only have a modest effect in slowing cognitive decline just like the other drug therapies.
• Use not well defined

Question 17

For patients that have Mild-Moderate Alzheimer’s disease, for drug treatment, the option available includes:\

1)

Answer 17

acetylcholinesterase inhibitor

Question 18

For patients that have Moderate-severe Alzheimer’s disease, there are 3 options for treatment:

1)
2)
3)

Answer 18

1) acetylcholinesterase inhibitor alone

2) NMDA blocker alone

3) acetylcholinesterase inhibitor + NMDA blocker

“Combination therapy is preferred.”

Question 19

In addition to directly addressing the cognitive decline associated with Alzheimer’s disease:

Concomitant Psychiatric Disorders are important to consider when treating patients with Alzheimer’s disease.

(e.g. depression and agitation)

1)How do we treat depression? What is important to consider?

Answer 19

-early in the disease patients with Mild impairment who understand the progressive nature of dementia may become depressed as they consider their future cognitive abilities.

1) Tx of depression in Alzheimer’s disease is the same as for any patient with depression. So, first line agents such as SSRIs are appropriate.
**It is important to AVOID antidepressants with ANTICHOLINERGIC effects, such as TRICYCLIC antidepressants.

Question 20

In addition to directly addressing the cognitive decline associated with Alzheimer’s disease:

Concomitant Psychiatric Disorders are important to consider when treating patients with Alzheimer’s disease.

(e.g. agitation and psychosis)

2) How do we manage? What are the non-pharmacological options? What are drug options?

Answer 20

• agitation and psychosis/hallucinations are common in patients with dementia
• agitation and psychosis/hallucinations occur as dementia progresses to more severe stages
• these symptoms are best managed with non-pharmacological adjustments such as redirection and a calm consistent environment.
• Unfortunately, these non-pharmacological management strategies may not be enough, and antipsychotics may be needed.

[brexpiprazole (Rexulti) is an antipsychotic with an FDA approved indication for agitation due to Alzheimer’s disease.]
- other antipsychotics such as olanzapine are often used off label.

remember - ALL antipsychotics have a BOXED WARNING for increased mortality when used for dementia related psychosis

*Additionally, antipsychotics are associated with an increased rate of cognitive decline when used in patients with dementia.**

Question 21

Because of these 2 concerns:

remember - ALL antipsychotics have a BOXED WARNING for increased mortality when used for dementia related psychosis

*Additionally, antipsychotics are associated with an increased rate of cognitive decline when used in patients with dementia. **

Antipsychotics should ONLY be used LAST Line in agitation or psychosis if patient poses harm to self or others. They should be used at low doses and for the shortest amount of time possible.

Question 22

Dementia and Alzheimer’s disease cannot be diagnosed with a signal test.

Instead, multiple signs and symptoms will be consistent with dementia or Alzheimer’s disease and a diagnosis will be made.

Signs and symptoms are collected from a patient and/or caregiver interview.

Screening and Diagnostic Tests
1)
2)
3)

Answer 22

1) Cognitive Testing - uses tools to determine presence of cognitive decline. It is non-invasive, inexpensive, and can be completed quickly.
- (MMSE) Mini-Mental State Examination
- (MoCA) Montreal Cognitive Assessment
[these screening tools include questions and activities that assess a patient’s orientation to time and place, attention, recall, naming, visual and spatial skills.]
- higher scores indicate a lack of cognitive impairment

2) Brain Imaging
- can identify structural abnormalities

3) Biomarkers (possible a measure of)
- cerebrospinal fluid
- blood
(These may be used to measure the concentrations of amyloid beta and tau in these fluids)

Question 23

What does the MMSE asses in patients?

Answer 23

Orientation

Registration

Attention and Calculation

Recall

Language/ability to communicate.

“second video rewatch 6:35min”

Question 24

While screening for and diagnosing cognitive impairment:
- it is important to rule out reversible causes of dementia.

Reversible causes of dementia include:

1
2
3
4

• these should be managed before a diagnosis of dementia is made.

Answer 24

1) Infection
- (e.g. UTI)
2) Depression and/or delirium
-
3) Vitamin B12 deficiency
-
4) Drugs affecting memory
-
- It is important to review medication list for drugs that affect memory or cognition and discontinue them if possible.

Question 25

Drugs that Can worsen Dementia: 1) 2) 3)

Answer 25

while reviewing a medication list for drugs that cause cognitive impairment, there are 3 groups of drugs to look for. 1) Antipsychotics- may increase the rate of cognitive decline in patients with dementia. - aripiprazole, chlorpromazine (1st &2nd generation) 2) (CNS) Central Nervous System depressants- decrease cognitive function -Barbiturates (phenobarbital) -Benzodiazepines (alprazolam, lorazepam) -Hypnotics (eszopiclone, zolpidem) -Opioids (hydrocodone, morphine) -Skeletal muscle relaxants (carisoprodol) 3) Drugs with anticholinergic effects- exacerbate the symptoms - antiemetics (prochlorperazine) - antihistamines (diphenhydramine, doxylamine) - central anticholinergics (benztropine) - peripheral anticholinergics (oxybutynin, dicyclomine) - tricyclic antidepressants (amitriptyline) **drugs in these 3 categories should be avoided in older adults BUT especially in patients with dementia to prevent worsening of symptoms.**

Question 26

acetylcholine binds to what receptors? _______1____ In the brain, acetylcholine binding to ____2_____ promotes memory, learning, attention and other cognitive functions. To end the action of acetylcholine, it is broken down by the enzyme _____3______

Answer 26

1) nicotinic receptors and muscarinic receptors 2) nicotinic receptors 3) acetylcholinesterase

Question 27

toxic amyloid beta plaques and Tau tangles destroy ___1___. With less of these present, there is less ______2___

Answer 27

1) cholinergic neurons 2) acetylcholine being made and then there is less acetylcholine available in the brain. Low levels of acetylcholine cause some symptoms of Alzheimer's disease including difficulties in forming new memories, paying attention, and learning. To compensate for this decreased acetylcholine, acetylcholinesterase inhibitors prevent the breakdown of acetylcholine. There by increasing the amount of acetylcholine in the synapse and allowing it to act longer and more strongly at acetylcholine receptors.

Question 29

Aricept Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 29

donepezil Class: acetylcholinesterase inhibitor, anti Indications: Alzheimer's disease MOA: - Alzheimer's disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the CNS. - - - drug inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis (breakdown) of acetylcholine; this causes an increase in acetylcholine. Dosage forms: ODT, tablet, (patch) - new brand name Adlarity Dosing: Start: 5mg PO every day at bedtime. Can increase to 10mg everyday at bedtime after [4-6 weeks]. Max dose: Contraindications: Warnings: *Cardiac effects, including bradycardia, syncope, QT prolongation. Anorexia/weight loss patients weighing less than < 55kg can have more nausea and weight loss. (NMS) Neuroleptic Malignant Syndrome and rhabdomyolysis (both rare) Side Effects: *Nausea, diarrhea (both dose-related, transient), insomnia, decreased appetite/weight loss Monitoring: Pearls/Notes: - **take at bedtime to help decrease nausea - nausea is a more common side effect than insomnia. However, if patient is experiencing insomnia, then dose can be moved to the morning. - *the adverse effects of acetylcholinesterase inhibitors is generally due to the fact that they raise acetylcholine levels in the brain and body. - due to the increase in acetylcholine, acetylcholinesterase inhibitors cause gastrointestinal adverse effects. These effects generally go away in 3-10 days after starting the drug or increasing the dose. There are some recommendations to decrease the likelihood of these effects from ever occurring. *Key recommendation* - Titrate slowly every (4-6 weeks) - if patent misses 3-7 days of dosing, Retitrate drug from starting dose. Drug-Drug/Food interactions: -** Use Caution with other drugs that can lower heart rate (e.g. beta-blockers, diltiazem, verapamil, digoxin) and with drugs that cause dizziness (e.g. antipsychotics, alpha-blockers, skeletal muscle relaxants. hypnotics, opioids). - - * drugs that have anticholinergic effects can reduce the efficacy of acetylcholinesterase inhibitors. Discontinue incontinence drugs if there is no benefit. - these drugs can increase gastric acid secretion; use cautiously with NSAIDs due to the risk of GI bleeding.

Question 30

Adlarity Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 30

donepezil Class: acetylcholinesterase inhibitor Indications: Alzheimer's disease MOA: - Alzheimer's disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the CNS. - - - drug inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis (breakdown) of acetylcholine; this causes an increase in acetylcholine. Dosage forms: transdermal patch 5mg/day & 10mg/day Dosing: Start- 5mg transdermal patch every week. (Patch is changed weekly, every 7 days) Can increase to 10mg every week after [4-6 weeks] "when changing patches, remove patch from the refrigerator and let it get to room temperature" Max dose: Contraindications: Warnings: * Cardiac effects: bradycardia, syncope, QT prolongation Side Effects: GI side effects (nausea, diarrhea) (both are dose related, transient) Insomnia Monitoring: For pharmacist: **Adlarity patches are stored in the refrigerator, let the patient know. Must be applied within 24 hours of it being removed from the fridge. Patches can be applied: - Upper or lower back (preferred- it demonstrates the best absorption through the skin) - Upper buttocks - Upper outer thigh - Patch should not be applied to the same location within 14 days. Pearls/Notes: - nausea is a more common side effect than insomnia. However, if patient is experiencing insomnia, then dose can be moved to the morning. - *the adverse effects of acetylcholinesterase inhibitors is generally due to the fact that they raise acetylcholine levels in the brain and body. - due to the increase in acetylcholine, acetylcholinesterase inhibitors cause gastrointestinal adverse effects. These effects generally go away in 3-10 days after starting the drug or increasing the dose. There are some recommendations to decrease the likelihood of these effects from ever occurring. *Key recommendation* - Titrate slowly every (4-6 weeks) - if patent misses 3-7 days of dosing, Retitrate drug from starting dose. Drug-Drug/Food interactions: -* Use caution with other drugs that lower heart rate (e.g. beta-blockers, diltiazem, verapamil, digoxin). - *Use caution with other drugs that may prolong the QT interval.

Question 31

Exelon Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 31

rivastigmine Class: acetylcholinesterase inhibitor Indications: Alzheimer's disease MOA: drug inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis (breakdown) of acetylcholine; this causes an increase in acetylcholine Dosage forms: capsule, patch* Dosing: Capsule: Start- 1.5mg PO BID. Can increase every {2 weeks} to 6mg BID Patch: Start with 4.6mg/24hrs Can increase [every 4 weeks] to 13.3mg/24hrs **remember patch is changed daily** Max dose: If Hepatic impairment: 4.6mg/24hrs max patch dose Contraindications: Warnings: **Cardiac effects, including bradycardia, syncope, QT prolongation. Anorexia/weight loss Patients weighting less than < 55kg can have more nausea and weight loss. (NMS) Neuroleptic Malignant Syndrome and rhabdomyolysis (both rare) Side Effects: -* nausea, diarrhea (both dose-related, transient), insomnia, decreased appetite/weight loss Monitoring: For pharmacist: - Change patch daily - Store patch at room temperature Patch can be applied: - upper and lower back (preferred- since it is less likely to be removed from the patient) - upper arm - chest Pearls/Notes: - Exelon patch has less GI side effects - Exelon patch Counseling: Apply patch the day after last oral dose; *rotate sites - do not use the same site for 14 days*. Does not contain metal (i.e. will not burn skin in MRI) - Exelon capsules should be taken with breakfast and dinner. - nausea is a more common side effect than insomnia. However, if patient is experiencing insomnia, then dose can be moved to the morning. - *the adverse effects of acetylcholinesterase inhibitors is generally due to the fact that they raise acetylcholine levels in the brain and body. - due to the increase in acetylcholine, acetylcholinesterase inhibitors cause gastrointestinal adverse effects. These effects generally go away in 3-10 days after starting the drug or increasing the dose. There are some recommendations to decrease the likelihood of these effects from ever occurring. *Key recommendation* - Titrate slowly every (4-6 weeks) - if patent misses 3-7 days of dosing, Retitrate drug from starting dose. Drug-Drug/Food interactions: -** Use Caution with other drugs that can lower heart rate (e.g. beta-blockers, diltiazem, verapamil, digoxin) and with drugs that cause dizziness (e.g. antipsychotics, alpha-blockers, skeletal muscle relaxants. hypnotics, opioids). - - * drugs that have anticholinergic effects can reduce the efficacy of acetylcholinesterase inhibitors. Discontinue incontinence drugs if there is no benefit. - these drugs can increase gastric acid secretion; use cautiously with NSAIDs due to the risk of GI bleeding.

Question 32

Razadyne Razadyne ER Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 32

galantamine Class: acetylcholinesterase inhibitor Indications: Alzheimer's disease MOA: drug inhibits centrally-active acetylcholinesterase, the enzyme responsible for hydrolysis (breakdown) of acetylcholine; this causes an increase in acetylcholine. Dosage forms: tablet, capsule, solution Dosing: IR tablet or solution: Start- 4mg PO BID Can increase [every 4 weeks] to 12mg BID ER capsule: Start - 8mg PO daily Can increase [every 4 weeks] to 24mg PO once daily. Max dose: If severe hepatic impairment/renal impairment- Do NOT Use Contraindications: Warnings: - ** Cardiac effects, including bradycardia, syncope, QT prolongation - anorexia/weight loss - patients weighting less than < 55kg can have more nausea and weight loss. - (NMS) Neuroleptic Malignant Syndrome and rhabdomyolysis (both rare) Side Effects: - nausea, diarrhea (both-dose related, transient), insomnia, decreased appetite/weight loss. - decreased heart rate Monitoring: Pearls/Notes: - galantamine IR should be taken with breakfast and dinner - galantamine ER should be taken with breakfast - galantamine solution can be mixed with liquid, drink immediately. - nausea is a more common side effect than insomnia. However, if patient is experiencing insomnia, then dose can be moved to the morning. - *the adverse effects of acetylcholinesterase inhibitors is generally due to the fact that they raise acetylcholine levels in the brain and body. - due to the increase in acetylcholine, acetylcholinesterase inhibitors cause gastrointestinal adverse effects. These effects generally go away in 3-10 days after starting the drug or increasing the dose. There are some recommendations to decrease the likelihood of these effects from ever occurring. *Key recommendation* - Titrate slowly every (4-6 weeks) - if patent misses 3-7 days of dosing, Retitrate drug from starting dose. Drug-Drug/Food interactions: - *Use Caution with other drugs that can lower heart rate (e.g. beta-blockers, diltiazem, verapamil, digoxin) and with drugs that cause dizziness (e.g. antipsychotics, alpha-blockers, skeletal muscle relaxants, hypnotics, opioids). - *Drugs that have anticholinergic effects can reduce the efficacy of acetylcholinesterase inhibitors. Discontinue incontinence drugs if there is no benefit. - These drugs can increase gastric acid secretion; use cautiously with NSAIDs due to the risk of GI bleeding.

Question 33

Namenda "NaMenDA" Namenda XR Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 33

memantine Class: (NMDA) N-methyl-D-aspartate antagonist Indications: moderate to severe Alzheimer's disease MOA: *Memantine blocks NMDA receptors, which inhibits Glutamate (an excitatory neurotransmitter) from binding and decreases abnormal neuron activation. (Glutamate, the primary excitatory amino acid in the CNS, may contribute to the pathogenesis od Alzheimer's disease by overstimulating various glutamate receptors leading to excitotoxicity and neuronal cell death.) Memantine is an uncompetitive antagonist pf the NMDA type of glutamate receptors, located ubiquitously throughout the brain. Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions. Excessive receptor activation as postulated to occur during AD, prevents magnesium ions from reentering and blocking the channel pore.   Dosage forms: tablet (5mg, 10mg), capsule XR (7mg, 14mg, 21mg, 28mg), oral solution (2mg/mL, 10mg/5mL) Dosing: IR: Start with 5mg by mouth once daily. Titrate *weekly* to 10mg PO BID ER: Start with 7mg PO once daily. Titrate *weekly* to 28mg PO once daily. **If CrCl is less than < 30mL/min: IR -MAX dose: 5mg PO BID for IR. ER -MAX dose: 14mg PO daily for ER. *Can switch IR 10mg BID to ER 28mg daily; Begin the ER the day after the last IR dose.* Contraindications: Warnings: Caution with drugs/conditions that increase urine pH, which decreases clearance of memantine. (e.g. Na bicarbonate, acetazolamide, renal tubular acidosis). Side Effects: Generally well-tolerated, can cause **dizziness, confusion, headache**, constipation, syncope. Monitoring: Pearls/Notes: -* ER capsule and Namzaric: DO NOT CRUSH or CHEW; capsules can be opened and sprinkled on applesauce (swallow immediately). - Oral solution: use provided dosing device and squirt into mouth Drug-Drug/Food interactions:

Question 34

Namzaric Class: Indications: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 34

memantine + donepezil Class: NMDA receptor antagonist Indications: moderate-severe Alzheimer's disease MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: -**combination therapy is preferred in moderate-severe Alzheimer's disease, so it is convenient that this combination is made** - All strengths of Namzaric contain 10mg of donepezil. - If patient is stable on donepezil 10mg, we can switch patient to Namzaric. Must be stable on donepezil 10mg prior to starting Namzaric (memantine 7mg/ donepezil 10mg PO QD HS) and titrate weekly. Drug-Drug/Food interactions:

Question 35

(Glutamate, the primary excitatory amino acid in the CNS, may contribute to the pathogenesis od Alzheimer's disease by overstimulating various glutamate receptors leading to excitotoxicity and neuronal cell death.) Memantine is an uncompetitive antagonist pf the NMDA type of glutamate receptors, located ubiquitously throughout the brain. Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions. Excessive receptor activation as postulated to occur during AD, prevents magnesium ions from reentering and blocking the channel pore. - - ->

Answer 35

This excessive NMDA activation results in a chronically open channel state and excessive calcium influx. This calcium overload is neurotoxic. And this leads to neuronal death and brain volume loss.