The Role of Acetylcholine in the Treatment of Alzheimer’s Disease Pharmacological Treatment Options for Alzheimer’s Disease: A Focus on First-Line Agents and Caution with Antipsychotics

Please respond to each classmate discussion post with at least 125 words and reference.
Discussion 1
The neurotransmitter acetylcholine, produced by cholinergic neurons, is vital in facilitating learning and memory transmission. As Alzheimer’s disease results in consistent cognitive and memory decline, the targeting of acetylcholine for the treatment of AD is critical (Morató et al., 2022). Even in the presence of hypometabolism and hypoperfusion, the preservation of M1 related to muscarinic acetylcholine receptors allows for the possibility of therapeutic growth efficacy through the cerebral acetylcholine level (Scarpa et al., 2020). As acetylcholine impairment is a significant deficit in AD, cholinesterase inhibitors are utilized in disease-modifying treatment to increase acetylcholine availability at synapses in the brain, which is crucial in treating AD-related dementia. This process underscores the importance of the cholinergic system as a therapeutic target for AD.
When treating AD with acetylcholine as a target, the first-line treatment involves drugs such as rivastigmine, Aricept, and galantamine. These drugs are crucial for the symptomatic treatment of AD and have a long-lasting effect. As acetylcholinesterase (AChE) – selective inhibitors, they inhibit acetylcholine breakdown, regulating its levels in the neurons (Haake et al., 2020). However, the use of antipsychotics is limited in AD patients due to their adverse effects. Even slight use of antipsychotic drugs in older individuals living with dementia, including AD patients, can lead to severe events such as pneumonia and even death (Taipale et al., 2019). Therefore, antipsychotic drugs are not recommended for treating AD patients.

Haake, A., Nguyen, K., Friedman, L., Chakkamparambil, B., & Grossberg, G. T. (2020). An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease. Expert opinion on drug safety, 19(2), 147-157.
Morató, X., Pytel, V., Jofresa, S., Ruiz, A., & Boada, M. (2022). Symptomatic and disease-modifying therapy pipeline for Alzheimer’s disease: Towards a personalized polypharmacology patient-centered approach. International Journal of Molecular Sciences, 23(16), 9305.
Scarpa, M., Hesse, S., & Bradley, S. J. (2020). M1 muscarinic acetylcholine receptors: a therapeutic strategy for symptomatic and disease-modifying effects in Alzheimer’s disease? Advances in pharmacology, 88, 277-310.
Taipale, H., Lampela, P., Koponen, M., Tanskanen, A., Tiihonen, J., Hartikainen, S., & Tolppanen, A. M. (2019). Antiepileptic drug use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer’s disease-matched cohort study. Journal of Alzheimer’s Disease, 68(1), 127-136.
Discussion 2
Acetylcholine and the Treatment of Alzheimer’s Disease
Alzheimer’s disease (AD) is a progressive and neurodegenerative disease (Chen et al., 2022). It is reflective of behavioral disorders, memory, and cognitive decline. Acetylcholine is a neurotransmitter that is essential to memory and the ability to learn (Chen et al., 2022). Cholinergic neurons secrete acetylcholine. There are two sites in the brain where cholinergic neurons are projected. There are cholinergic neurons in the nucleus basalis. With AD, there is degeneration of the nucleus basalis which causes a decrease in cortical cholinergic innervation (Boland & Verduin, 2022). The degree of neuronal loss reflects the extent of dementia, and the cholinergic deficiency is believed to cause the cognitive decline in alzheimer’s disease (Boland & Verduin, 2022). This is why drugs promoting acetylcholine signaling benefit this disease. A decrease in acetylcholine transferase activity indicates damage to the cholinergic system. The result of the damaged system regulates and promotes alterations in amyloid precursor protein metabolism and tau phosphorylation, causing neurotoxicity, neuroinflammation, and neuronal death (Chen et al., 2022). This leads to impaired attention, learning, sleep regulation, and memory (Chen et al., 2022).
First Line Agents for AD
Donepezil is a clinically approved acetyl-cholinesterase inhibitor (AChEI) for the promotion of cognitive function in AD and approved as a first-line drug for symptomatic therapy of AD (Chen et al., 2022). This medication has been shown to protect neurons and nerves which is essential to the pathogenesis of AD. Rivastigmine is approved for the symptomatic treatment of mild to moderate AD. The mechanism of action is by increasing acetylcholine in the brain which allows the nerve cells to communicate (Chen et al., 2022). Tacrine was the first AChEI approved for symptomatic AD. It was pulled from the market due to acute liver injury from elevated serum aminotransferase (Chen et al., 2022). Galantamine is an allosteric potentiator of a4B2 and presynaptic a-7 nicotinic acetylcholine receptors (Chen et al., 2022). The dual action of this medication has much clinical significance in the treatment of AD.
Antipsychotics and AD
It is recommended that antipsychotics not be used to treat AD or the geriatric population. If they have to be used, the benefit must outweigh the risk (Tapiaine, 2020). The Journal of the American Geriatrics Society warns that the use of antipsychotics is linked to increased head injuries in AD patients (Tapiaine, 2020). Antipsychotics can cause sedation, orthostatic hypotension, and arrhythmias which can lead to falls. These drugs have been used to treat patients with AD when behavior has been severe and no other medications are effective (Tapiaine, 2020). Pharmacists must provide education to caregivers regarding this medication. There are new drugs in trial studies to treat AD.

Boland, R., Verduin, M. L. (2022). Kaplan & saddock’s synopsis of psychiatry (12th ed.). Wolters Kluwer. ISBN: 9781975145569.
Chen, Z. R., Huang, J. B., Yang, S. L., Hong, F. F. (2022). Role of cholinergic signaling in alzheimer’s disease. PubMed Central. 27(6), 1816 https://doi.10.3390/molecules27061816
Tapiainen, V. (2020). More evidence for caution in use of antipsychotics for alzheimer’s patients. U.S. Pharmacist. https://www.uspharmacist.comLinks to an external site.

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