Parkinson's Disease Flashcards
Explain the pathophysiology of Parkinson’s Disease
PD is characterised by a severe loss (80%) of pigmented dopaminergic neurons in the substantia nigra of the midbrain – leading to a loss of motor neurons projecting to the corpus striatum.
A diminished nigrostriatal pathway reduces the ability to modulate activity in the basal ganglia-thalamocortical circuit. As a result of a loss of dopaminergic neurons, there is an uncontrolled inhibition of the thalamus, leading to reduced motor cortex function, and movement. As a result, symptoms such as dyskinesia (slow movement), postural instability, rigidity and tremors may arise.
Explain the clinical presentation of Parkinson’s Disease
Bradykinesia – slowness of movements, progressive reduction in amplitude of repeated movements, delay in initiating movements, and freezing of gait and lack of arm swinging due to slowness of movement
Resting tremor – at 4-6 Hz, generally asymmetrical at onset
Rigidity – increased resistance within the range of passive movement of a joint
Postural and gait abnormalities - shuffling steps, stooped posture, takes extra steps to turn, balance impaired and requires several steps to regain balance
Explain the role in therapy, mechanism, and side effects of Levodopa
Role in therapy: preferred initial dopaminergic therapy to improve motor functions for patients with early PD, studies show that levodopa provides the greatest clinical benefit for motor symptoms.
Mechanism: Levodopa is converted by amino acid decarboxylase into dopamine in the brain and binds to dopamine receptors on the neurons in the basal ganglia, improving motor function.
Side effects: nausea, vomiting, dizziness, headache, constipation, later can lead to motor fluctuations, dyskinesia and other “on-off phenomenon”
Explain the role and mechanism of Dopa-Decarboxylase Inhibitors
Role in therapy: used in combination with levodopa to improve efficacy and reduce side effects of levodopa therapy.
Mechanism: prevents peripheral conversion of levodopa by inhibiting dopa-decarboxylase, thereby increasing the amount of levodopa that reaches the brain, allowing for a greater amount of levodopa to be converted to dopamine and improving motor function. Reducing peripheral dopamine will prevent binding to dopamine receptors in the CTZ which induces nausea and vomiting.
State the dosing regimen of levodopa/carbidopa
Dose: initially 100mg/25mg THREE times daily
Increase by 100/25mg daily or on alternating days according to tolerability
Max 2g/daily - consider switching formulations if necessary
Explain the role in therapy, mechanism, and side effects of dopamine agonists
Role in therapy: originally first-line for early-stage PD (<40 y.o), or add-on therapy in advanced PD, has less motor complications than levodopa - however, considered to be less effective
Mechanism: Dopamine agonists work by binding to and activating dopamine receptors in the brain, thereby mimicking the effects of dopamine.
Side effects: N/V, impulse control, hypersexuality, compulsive shopping
State the 3 dopamine agonist drugs funded in NZ
Apomorphine, pramipexole, ropinirole
State TWO MAO-B inhibitors available in NZ
Rasagiline, Selegiline HCl
Explain the role in therapy and mechanism of MAO-B inhibitors
Role in therapy: monotherapy for PD, or as adjunct to levodopa for end-of-dose fluctuations
Mechanism: irreversibly binds to and inhibits monoamine oxidase B, an enzyme involved in the degradation of dopamine in the brain, resulting in an increase of dopaminergic activity and improvement of PD symptoms.
State TWO COMT inhibitors available in NZ
Entacapone, tolcapone
Explain the role in therapy and mechanism of COMT inhibitors
Role in therapy: adjunct to levodopa in combination with DDI to reduce ‘wearing off’ effect
Mechanism: inhibits COMT, an enzyme involved in the degradation of levodopa in the bloodstream before it reaches the brain, resulting in more levodopa and dopamine in the brain, which can alleviate symptoms of PD
Explain the role in therapy and mechanism of Amantadine
Role in therapy: Amantadine is used in secondary parkinsonism or as initial therapy or adjunct to Levodopa
Mechanism: weak dopamine agonist
State 5 non-pharmacological management options for Parkinson’s Disease
Exercise and formal exercise rehabilitation - help overcome disabilities (abnormal gait)
Occupational therapy - continued activity and employment is likely to improve self-esteem and maintain patient’s role in the family
Speech therapy - voice training to improve soft speech (hypophonia)
Managing weight loss and constipation
Support and counselling - can assist in development of self-management techniques
Briefly summarise the epidemiology of Parkinson’s Disease
The mean age of onset is typically 65 years.
Increasing prevalence over the last decades, is not completely attributed to ageing population.
Occurs more in caucasian.
1.4 times more common in men than women.
Explain how nausea is managed in Parkinson’s Disease
Nausea can occur in PD patients due to their dopaminergic medications, which may bind to dopamine receptors in the CTZ and induce N/V.
Domperidone is preferred as it does not readily cross the BBB, meaning less extrapyramidal symptoms. Ondansetron can also be considered, but it increases the risk of extrapyramidal symptoms. Cyclizine is also an option, but consider the sedation risk.
Domperidone dose: 10mg 3-4 times daily.
Other options:
- Increase carbidopa dose
- Take levodopa with food (but beware of reduced absorption)
- Avoid triggers
- Stay hydrated
