Chapter 38: Parkinson’s Disease – Dopaminergic Drug Therapy

Parkinson's disease (PD) is a progressive neurodegenerative disorder defined by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), leading to critical depletion of dopamine in the corpus striatum and a subsequent breakdown in motor communication. The pathology is characterized by the accumulation of alpha-synuclein and ubiquitin aggregates known as Lewy bodies, which appear in various brain regions, correlating with the onset of both motor symptoms (like the cardinal feature of bradykinesia, rigidity, and rest tremor) and nonmotor symptoms. When evaluating a patient, healthcare providers must first rule out drug-induced parkinsonism (DIP), often caused by medications such as valproic acid or certain antipsychotics. Treatment aims to maintain the patient's quality of life by managing these varied motor and nonmotor manifestations, with therapy selection guided by factors like patient age, symptom severity, and functional disability, since no disease-modifying agents currently exist. Although the immediate initiation of pharmacotherapy is often preferred to delay symptom progression, the high-potency agent levodopa, typically administered with carbidopa to inhibit peripheral breakdown and enable better blood-brain barrier penetration, is often reserved for patients with moderate to severe impairment. Moderate-potency options, Dopamine Agonists (DAs) like pramipexole and ropinirole, are frequently used as monotherapy in younger individuals to minimize the risk of developing dyskinesia, although DAs increase the risk of adverse events such as impulse control disorders (ICDs) and sleep attacks. Mild-potency drugs include MAO-B inhibitors (selegiline, rasagiline), which enhance dopamine concentrations by inhibiting its metabolism, and amantadine, which is particularly useful for dyskinesia. Patients experiencing "wearing-off" from levodopa can have COMT inhibitors, such as entacapone, added to their regimen to prolong levodopa’s half-life. Management also encompasses treating common nonmotor issues, such as using rivastigmine or donepezil for PD-related dementia, and utilizing lifestyle adjustments like increasing exercise for mobility and strategic dietary timing to separate high-protein intake from levodopa doses.