NR546 WEEK 8 FINAL EXAMINATION PREPARATION: COMPREHENSIVE PSYCHOPHARMACOLOGY 200+ Q&A | SYNTHESIS OF TREATMENT PLANS, SPECIAL POPULATIONS, & BOARD-STYLE QUESTIONS FOR PSYCHIATRIC MENTAL HEALTH NP CERTIFICATION

Early (1-3 years) signs of AD

short term memory deficits

disoriented to date

diminished recall of recent events

mild language and decision-making deficits

mild problem copying figures (clock drawing)

social withdrawal

mood change

personality changes

problems with managing finances

Middle (2-8 years) stage of AD

disoriented to date and place

may get lost in familiar places

impaired learning new skills

agitation, aggression, restlessness, or anxiety

difficulty with ADLs such as cooking and grooming

Late (6-12 years) stage of AD

disoriented to person, time, or place

non-verbal

long term memory diminished

unable to groom or dress

progress to need for total care at end stage

incontinent

motor or verbal agitation

Alzheimer's disease (AD) demographic

most prevalent in people over age 65

African American (13.8%),

Hispanics (12.2%),

non-Hispanic whites (10.3%),

American Indian and Alaska Natives (9.1%),

Asian and Pacific Islanders (8.4%)

Genetics r/t AD

Genes appear to play a strong role, with late-onset AD showing heritability of 58-79% and early-onset AD showing over 90%

Neuroanatomy r/t AD

amyloid plaques and neurofibrillary tangles.

atrophy of hippocampus and cerebral cortex.

Neural Networks r/t AD

damage to synapses, mitochondrial abnormalities, and inflammatory processes

Neural Signaling r/t AD

decreased acetylcholinesterase activity and a permanent loss of cholinergic neurons

Acetylcholine (ACh) is a neurotransmitter necessary for processing memory and learning.

Diagnosis of AD

comprehensive health history is key to gather clues

Rule out other causes of dementia

Early AD may include anxiety, irritability, and sleep disruption

new-onset mental health symptoms in late 50s and 60s may be in the early stage of AD

Cholinesterase Inhibitors (ChEIs)X

do not change the progression of AD

provide some alleviation of symptoms

eg. donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, Razadyne ER),

donepezil (Aricept)

Mechanism of Action

inhibits centrally active acetylcholinesterase

donepezil (Aricept)

Common Side Effects

gastrointestinal symptoms (nausea and diarrhea)

headache

dizziness

muscle weakness

donepezil (Aricept)

Precaution

sick sinus syndrome

seizure disorder

donepezil (Aricept)

Prescribing Pearls

Taper to avoid withdrawal effects.

Donepezil (Aricept) is approved to treat moderate to severe AD at 23 mg/day dose, but there is minimal improvement in cognitive functioning when compared to a 10 mg/day dose. At the higher dose, donepezil has a higher incidence of adverse effects.

When Donepezil (Aricept) is added to CYP2D6 or CYP3A4, there is a possibility of peripheral side effects, and inducers of CYP2D6 and CYP3A4 may increase the rate of elimination

rivastigmine (Exelon)

Mechanism of Action

acts centrally for both acetylcholinesterase and butyrylcholinesterase, thereby potentially increasing its efficacy.

rivastigmine (Exelon)

Common Side Effects

Common Side Effects

gastrointestinal symptoms (anorexia, nausea, vomiting, or diarrhea)

weakness

dizziness

tremor

rivastigmine (Exelon)

Precautions

Precautions

asthma or COPD

sick sinus syndrome

GI Bleeding

weight < 50 kg

Prescribing Pearls

Rivastigmine (Exelon)

Prescribing Pearls

Rivastigmine (Exelon) is administered orally or topically (transdermal patch).

The transdermal patch is used for dementia associated with Parkinson's disease.

Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine (Exelon) metabolism

galantamine (Razadyne, Razadyne ER)

Mechanism of Action

Mechanism of Action

Galantamine (Razadyne, Razadyne ER) acts by elevating acetylcholine (Ach) in the cerebral cortex, modulating the nicotinic Ach receptors to increase Ach release from existing presynaptic nerve terminals. It also increases glutamate and serotonin levels; however, the benefits of this action are unknown

Common Side Effects

galantamine (Razadyne, Razadyne ER)

Common Side Effects

gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia, and weight loss)

headache

dizziness

fatigue

galantamine (Razadyne, Razadyne ER)

Precautions

Precautions

NSAID use

GI bleed

asthma or COPD

concurrent use with medications that slow or decrease heart rate

Contraindications

galantamine (Razadyne, Razadyne ER)

Contraindications

severe hepatic impairment

severe renal impairment

Prescribing Pearls

galantamine (Razadyne, Razadyne ER)

Prescribing Pearls

There are two major metabolizing enzymes CYP3A4 and CYP2D6 that increase galantamine (Razadyne, Razadyne ER) concentrations or reductions in clearance and anticholinergic side effects when given concurrently with inhibitors of these enzymes

N-methyl-D-aspartate (NMDA) Receptor Antagonist

Memantine is the only NMDA approved to manage moderate to severe AD. Based on clinical trials, improvement is modest

Memantine (Namenda)

Mechanism of Action

Mechanism of Action

prevents glutamate, an excitatory neurotransmitter, from binding at the receptor site. NMDA receptors control activity throughout the brain by regulating how much calcium enters the nerve cell. An overproduction of the NMDA receptor and excess glutamate can lead to excessive calcium entering the cell and disrupting information processing. Blocking NMDA receptors protects neurons from the effects of too much glutamate without affecting normal neurotransmission

Common Side Effects

Memantine (Namenda)

Common Side Effects

gastrointestinal symptoms (constipation, diarrhea, and weight gain)

urinary frequency

confusion

dizziness

headache

cough

Precautions

Memantine (Namenda)

Precautions

concurrent use with (amantadine, rimantadine, ketamine, or dextromethorphan)

severe hepatic impairment

severe renal impairment

medications or conditions that increase the pH of the urine

Prescribing Pearls

Memantine (Namenda)

Prescribing Pearls

This is used as monotherapy or in conjunction with ChEIs; when given with ChEIs, fall precautions are required and driving is forbidden due to delayed reactions.

Minimal inhibition of CYP450 enzymes CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 occurs, which means there are no pharmacokinetic interactions with medications metabolized by these enzymes

N-methyl-D-aspartate (NMDA) Receptor Antagonist

Prescribing Pearls

Prescribing Pearls

Memantine is associated with an increased life expectancy when compared to donepezil (Procyshyn et al., 2018).

If treatment failure occurs, 50% of individuals respond to a different agent (Procyshyn et al., 2018).

Educate clients and families that medications cannot halt or reverse the progression of Alzheimer's disease.

Consider goals of care in the selection of medication. Is the management of a specific symptom or behavior the goal? Is the associated risk of the medication worth the potential benefit? These goals will inform the selection of an agent.

Donepezil at a higher dose has a higher incidence of adverse effects without increased cognitive benefit.

Rivastigmine (Exelon) is available in oral form or transdermal patch.

The transdermal patch is used for dementia associated with Parkinson's disease. Medications that induce or inhibit CYP450 metabolism will not modify rivastigmine metabolism (Chisholm-Burns et al., 2019).Antipsychotics are not recommended for the treatment of dementia-related to agitation and behavioral symptoms (Stahl, 2021).

Lifespan Considerations in treating AD

Cholinesterase inhibitors are not recommended in pregnancy and lactation.

The first-line pharmacologic treatment of aggression and agitation in dementia

SSRI/SNRI therapy

Cleo is a 65-year-old male diagnosed with mild cognitive changes related to Alzheimer's disease. He also has anxiety, COPD, and smokes cigarettes. Which of the following medications is appropriate for Cleo?

donepezil

A patient diagnosed with Alzheimer's disease has decided to stop treatment. The NP has educated the client that medication discontinuation will result in the return of cognitive symptoms and the medication may not work as well if restarted. The client would still like to stop the medication due to the gastrointestinal side effects. Which of the following medications requires tapering?

donepezil

Rationale:

Donepezil requires tapering. Rivastigmine and Galantamine do not require tapering.