Alzheimer’s Disease Angela Singh, PharmD Associate Professor of Pharmacy Practice Florida A&M University College of Pharmacy & Pharmaceutical Sciences

Objectives Understand the pathophysiology of Alzheimer’s Disease (AD) Identify cognitively impairing medications when given a patient list List the available products used for the management of AD including brand and generic names Describe the mechanism of action of pharmacotherapy for AD Identify potential drug interactions while reviewing a patient profile Recommend solutions for adverse effects experienced by patients receiving therapy for AD

What is dementia?

Types of Dementia Alzheimer’s Disease (AD) Lewy Body Dementia Vascular Dementia Parkinson’s Related Dementia

Alzheimer’s Disease (AD) Most common form of dementia Increasing prevalence with increasing age Characterized by Presence of amyloid plaques Presence of neurofibrillary tangles Loss of Cortical neurons

Pathophysiology

MRI Scan

Differential Diagnosis Anemia Hypothyroidism Low Vitamin D Levels Infections UTI HIV Use of Cognitively Impairing Medications

Depression versus AD DEPRESSION Abrupt in onset Short duration Previous psychiatric history Complaints of memory loss “I don’t know” answers Fluctuating cognitive loss Equal memory loss for remote and recent memory Depressed mood occurs first DEMENTIA Insidious in onset Long duration No psychiatric history Often unaware of memory loss Near miss answers Stable cognitive loss; progressive over time Memory loss is greatest for recent events Memory loss occurs first

What are some medications that are cognitively impairing?

Diagnostic Test Mini Mental Status Examination Formal Neuropsychiatric Testing MRI or CT scans Lab CBC Thyroid Vitamin B-12 Iron Urinalysis Syphilis HIV

AD: Clinical Features Impairment of Memory Changes in Personality Impairment of Judgment Loss of Language Skills Loss of Executive Function Social Withdrawal Apathy Loss of orientation

Pharmacotherapy

Acetylcholinesterase Inhibitors How do these agents work? Take 4-6 weeks for onset of therapeutic effect to be seen. Patient should be on the agent a minimum of 3 months without improvement before changing to another agent. Donepezil (Aricept®) Rivastigmine (Exelon®) Galantamine (Razadyne®) Tacrine (Cognex®)

Donepezil (Aricept®) Indicated for the management of mild to severe AD Drug Interactions Anticholinergics 3A4 & 2D6 Inhibitors/Inducers It is given once daily due to its long half-life. Available as a tablet and an orally disintegrating tablet (ODT). Common Side Effects: nausea, vomiting, diarrhea, insomnia (8%), vivid dreams, dizziness. Give in the morning with food.

Rivastigmine (Exelon®) An inhibitor of both acetylcholinesterase and butyrylcholinesterase. Indicated for management of mild to moderate AD Drug Interactions Anticholinergics 3A4 & 2D6 Inhibitors/Inducers Short elimination half-life necessitates twice daily dosing. Available as liquid, pill, patch. Side Effects: GI side effects are more frequent (48% - 50%), dizziness, insomnia. Must be given with food.

Galantamine (Razadyne ®) Selectively inhibits acetylcholinesterase and also modulates nicotinic receptors. Indicated for mild to moderate disease Drug Interactions Anticholinergics 3A4 & 2D6 Inhibitors/Inducers Available as a ER capsule, solution, tablet Due to its short elimination half-life, two doses are required daily when using the tablet or solution. The ER capsule is dosed once daily. Side effects: nausea, vomiting, diarrhea, dizziness.

Memantine (Namenda®) An N-methyl-D-aspartate antagonist approved for moderate to severe Alzheimer’s disease.

Pathophysiology of AD: Basis for Memantine Glutamate is the main excitatory neurotransmitter in the CNS. One type of glutamate receptor includes the NMDA (N-methyl-D-Aspartate) receptors; once activated, they generate a long-lasting influx of calcium into neurons which is thought to be involved in a cellular process that underlies learning and memory. In AD, an increase of glutamate is thought to lead to excessive activation of NMDA receptors with consequent intracellular accumulation of calcium initiating a cascade of events which leads to neuronal death.

Mechanism of Action of Memantine An NMDA receptor antagonist Reduces overstimulation of the NMDA receptors (caused by abnormally high concentrations of glutamate) and restore normal receptor-signaling function. By reducing excitotoxicity will prevent neuronal calcium overload therefore preventing further cell damage and cell death.

Memantine Indicated for moderate to severe AD Formulations include tablets, ER tablets, solution. Side Effects Dizziness, tachycardia, diarrhea, insomnia, headache, restlessness, akathisia, nausea

Questions Angela Singh, PharmD Office #345