neurodegenerative disorders
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) (Moore, Shpiner, & Luca, 2019). PD has been traditionally considered as a pure movement disorder secondary to focal degeneration of dopaminergic neurons in the substantia nigra, but, in recent years, the clinical phenotype has been better illuminated, showing that PD is a multisystem neurodegenerative disorder with motor and non-motor features. Among motor symptoms and signs, the cardinal ones (bradykinesia, rest tremor, and rigidity) are mainly the loss of dopaminergic neurons, but those involving posture, balance, and gait are largely secondary to degeneration of nondopaminergic pathways and significantly contribute to impairment and disability in advanced PD patients (Moore, Shpiner, & Luca, 2019). Nonmotor features result from multiple neurotransmitter deficiencies in the central and peripheral nervous system and include psychiatric such as: depression, apathy, hallucinations, and delusions. Autonomic includes constipation, orthostatic hypotension, and urinary and genital disturbances. Cognitive impairment such as: involvement of executive functions, memory, sleep disorders, olfactory dysfunction, and pain that together contribute to worsening the quality of life and patient’s disability (Moore, Shpiner, & Luca, 2019).
Cardinal motor features of Parkinson’s disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation (Moore, Shpiner, & Luca, 2019). Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways (Moore, Shpiner, & Luca, 2019). Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment (Moore, Shpiner, & Luca, 2019).
Pharmacological therapy is based on levodopa and dopamine agonists and is very successful in the early stages of the disease, when dopaminergic symptoms and signs are predominant and long term motor complications still have not developed, but other treatment strategies are necessary as time passes (Hajj, 2018). Long term levodopa-induced motor complications include motor fluctuations and dyskinesia and affect almost all PD patients at some point during the disease course, with relevant implications in global health status (Hajj, 2018). Despite various pharmacological approaches, as well as more invasive strategies including devices and functional neurosurgery, being available to manage such complications, many patients remain significantly disabled, and a fully satisfying management of motor complications is still an unmet need of PD therapy. Nonmotor symptoms and signs are integral to PD at onset and throughout the disease course, but to date their treatment is largely unsatisfactory (Hajj, 2018).
References
Hajj, R. (2018). Parkinson Disease Therapies and Drugs. Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 151–158. doi: 10.1007/978-981-13-0944-1_13
Moore, H., Shpiner, D. S., & Luca, C. C. (2019). Management of Motor Features in Advanced Parkinson Disease. Clinics in Geriatric Medicine. doi: 10.1016/j.cger.2019.09.010
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Heart Failure
Pathophysiology is a vital discipline in medicine and is generally useful for diagnosis and patient care. The disease-related to pathophysiology is heart failure. Wright and Thomas (2015) explain that pathophysiology in the management of heart failure ensures that patients are optimized on a maximum tolerated dose of medicine to treat heart failure with reduced ejection fraction. Heart failure is a complex clinical syndrome whereby the heart is not able to attain the metabolic demands of the body. The reasons underlying the mismatch can be multifactorial. However, the various pathological conditions make the treatments and management of the condition to be complex. Therefore, pathophysiology is essential in minimizing the burden on the condition. Heart failure is on the increase for the past decade leading to the heightening of the adult population to around 1% to 2%. The male population is the greatest affected gender, with an estimated 33% of men above 55 years old having the condition as compared to the 28% in women (Farmakis et al., 2015). Pathophysiology seeks to redress the balance through initiating contemporary measures. However, the measures have become damaging to the diseases and can lead to worsening cardiac output that can result in additional stress to a failing heart.
References
Farmakis, D., Parissis, J., & Filippatos, G. (2015). Acute heart failure: epidemiology, classification, and pathophysiology. Oxford Medicine Online, 2(1), 2-10. doi:10.1093/med/9780199687039.003.0051
Wright, P., & Thomas, M. (2018). Pathophysiology and management of heart failure. Clinical Pharmacist, 2(1), 1. doi:10.1211/cp.2018.20205742