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Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
Combining levodopa with a peripheral decarboxylase inhibitor prevents most nausea caused by the peripheral conversion of levodopa to dopamine. When occurring, it can be minimised by slow dose titration. Alternatively, the dopamine receptor antagonist domperidone can be used to block peripheral dopamine-induced adverse effects as it has a very poor penetration of the blood-brain barrier. It is usually possible to reduce this medication after a few weeks on levodopa therapy. Other potential complications include hallucinations, orthostatic hypotension (see page 318), delirium and features of the dopamine dysregulation syndrome (see later). Patients and their next of kin should be warned about these when starting treatment.7
Answers
Published in Andrew Schofield, Paul Schofield, The Complete SAQ Study Guide, 2019
Andrew Schofield, Paul Schofield
Parkinson’s disease is characterised by bradykinesia, increased tone and tremor. It results from degeneration of dopaminergic neurones within the substantia nigra. Dopamine is responsible for inhibition of muscular activity, and degeneration means its inhibitory effect is less than the excitatory effect of acetylcholine. Levodopa is commonly given to patients with Parkinson’s disease, but over time its effects are reduced. This leads to fluctuating responses to the drug, dyskinesia, choreiform movements and dystonias. Also, the duration of its action is reduced. For these reasons, it is often held in reserve for younger patients, and other medications are tried first. Examples of other treatments include dopamine agonist and amantidine.
Special considerations: Parkinson’s disease
Published in Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor, Essentials of Geriatric Neuroanesthesia, 2019
Some common side effects of levodopa include nausea, orthostatic hypotension, somnolence, dizziness, and headache. Side effects are decreased by the use of peripheral decarboxylase inhibitors. Elderly patients are susceptible to more serious adverse reactions like confusion, hallucinations, and agitation. Wearing-off phenomenon is a complication that starts within years of treatment and is characterized by involuntary movements like dyskinesia and others. The effect of levodopa can begin to wear off approximately 2 hours after a dose.
Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach
Published in Expert Review of Neurotherapeutics, 2023
Andrew Lees, Eduardo Tolosa, Fabrizio Stocchi, Joaquim J. Ferreira, Olivier Rascol, Angelo Antonini, Werner Poewe
In the early years of ‘levodopa combination’ therapy, many patients received high doses of levodopa. NonselectiveNon-selective monoamine oxidase inhibitors used to treat depression in the 1960ʹs potentiated the effects of levodopa but could not be used safely because of dangerous elevations of blood pressure [10]. The emergence of motor fluctuations and disabling levodopa-induced dyskinesias (LID) as a complication of sustained levodopa therapy led to renewed efforts to improve its bioavailability and reduce its enzymatic breakdown in the peripheral tissues and the brain [9]. In the late 1970s, the first selective MAO-B inhibitor, selegiline was introduced and shown to have mild symptomatic benefits and the capability to reduce the severity of mild wearing-off effects in levodopa treated patients [11]. Two newer MAOB inhibitors – rasagiline and safinamide – are also now available but there is no evidence that they are superior to selegiline [12–14]. The most recent enzymatic refinement to levodopa therapy was the introduction of COMT inhibitors in 1997. Three drugs are currently licensed – tolcapone, entacapone and (the most recently developed) opicapone – all of which smooth out motor fluctuations and reduce the severity of OFF periods.
An evaluation of the efficacy and value of CVT-301 for the treatment of Parkinson’s disease
Published in Expert Opinion on Pharmacotherapy, 2021
Fabrizio Stocchi, Laura Vacca, Andrea Grassi, Margherita Torti
Levodopa (LD) is the most effective and widely used treatment of Parkinson’s disease (PD). When LD is first introduced, therapeutic benefit is maintained beyond the actual half-life of the single dose, thanks to the ability of survivor neurons to store and gradually release dopamine [1,2]. As PD progresses, patients begin to experience fluctuations in their motor response due to the progressive reduction of the long-term response and the following overlapping between the pharmacodynamic response and pharmacokinetic profile [3,4]. The short half-life of LD can also induce pulsatile stimulation of striatal dopamine receptors, leading to the occurrence of motor fluctuations [4–6]. Moreover, variability in the LD absorption rate caused by delayed gastrointestinal transit time [7–9] can affect the LD onset of action which can be delayed for few hours (delayed ON) or totally missing (no-ON) [10].
Complications of levodopa therapy in Parkinson’s disease
Published in Expert Opinion on Orphan Drugs, 2019
Jordan Dubow, C. Warren Olanow
The manifestations of motor fluctuations and dyskinesia have been well characterized. The most common type of motor complication is the wearing ‘Off’ response or end of dose deterioration, which entails a return of parkinsonian features (i.e. tremor, bradykinesia, rigidity) following a given levodopa dose prior to the onset of benefit from the subsequent dose. Early in the disease, the benefit following a dose of levodopa may last for 6 hours or longer, but as the disease progresses the duration of benefit begins to shorten and to approximate the half-life of the drug (approximately 90 minutes). Additionally, with continued levodopa treatment and disease progression, patients can experience a variable response following each dose: this could include a normal full response, a delayed response (delayed-on), a partial response (partial ON) and no response at all (no-‘On’ response). Typically, a patient will notice an improvement in motor symptoms within about 45 minutes after taking a standard levodopa dose. However, these responses can be variable and unpredictable, leaving a patient unsure when, and to what extent, their dose of levodopa is going to work. Although less common today, PD patients can also experience sudden ‘Offs’, where the benefit of medication suddenly stops working and parkinsonian symptoms rapidly recur. This is known as the ON-OFF response.