Parkinson's Disease Flashcards
Pathological hallmark
Dopaminergic neuron loss in the substantia nigra pars compacta (SNpc), with a-synuclein containing Lewy bodies and Lewy neurites.
Basal Ganglia
Parkinsonian Syndrome
Dystonia
Chorea - Ballismus
Parkinsonian Syndrome
Rigidity
Akinesia / bradykinesia
Resting ‘pill rolling’ tremor
Clinical Features
Tremor Muscular rigidity Akinesia Rest tremor Gait and postural impairment
2 types of PD
Tremor dominant PD
Non-tremor dominant PD
Non-motor features of PD
Olfactory dysfunction Cognitive impairment Psychiatric symtpoms Sleep disorders Autonomic dysfunction Pain Fatigue
REM sleep behaviour disorder in PD treatment
Clozepam or melatonin at bedtime
Neuronal loss in PD regions
Locus ceruleus Nucleus basalis Meynert Pedunculopontine Raphe nuclei Dorsal motor nucleus of vagus Amygdala Hypothalamus
First gene to be associated with inherited PD in 1997
SNCA
Most common cause of dominant and recessive PD
Dominant: LRRK2
Recessive: Parkin
Greatest risk factor for PD
Mutation in GBA (encodes B-glucocerebrosidase)
Drugs used in PD Treatment
Levodopa
Dopamine
Monoamine Oxydase Type B Inhibitors
Amantadine
Bradykinesia and Rigidity
Respond to Dopaminergic treatment early in disease
MAOB Inhibitors
Only moderately effective, Levodopa and dopamine agonists needed for more severe symptoms
Tremor
Responds inconsistently to Dopamine replacement therapy.
Anticholinergics
Useful for tremor. Trihexyphenidyl, or clozapine also work
Adverse drug reactions (Dopamine agonists and Levodopa)
Nausea, daytime somnolence and oedema.
Dopamine agonists avoided in
Patients with history of addiction, OCD and impulsivity disorder.
Adverse drug reactions (Dopamine agonists)
Associated with hallucinations - should not be prescribed in the elderly, especially those with cognitive impairment.
Adverse drug reactions (Levodopa - long term use)
Long term use is associated with motor complications (dyskinesia and motor fluctuations)
Long-term complications of dopaminergic therapies for PD
Motor fluctuations
Non-motor fluctuations
Dyskinesia
Drug induced psychosis
Management of complications of long term dopaminergic therapies
Strategies to reduce dopamine fluctuations:
Dopamine agonist
MAOB inhibitor
Catecholo-O-methyltransferase (COMT) inhibitor - entacapone
Psychosis in PD is managed with clozapine (or quetiapine)
Depression in PD patients
SSRIs
TCA
Visual hallucinations in PD
Cholinesterase inhibitors, such as Rivastigmine, can reduce hallucinations.
Late stage dementia in PD
Tx: Rivastigmine
Dopamine Agonist examples
Cabergoline
Bromocriptine
Ropinirole
Pergolide
Bromocriptine
Dopamine receptor agonist used when levodopa therapy is not adequate or not well tolerated.
Selegiline
MAO-B inhibitor - enzyme for which dopamine is a substrate. Reduces the metabolism of dopamine in the brain and potentiates the action of L-dop.
Effective early and late in the disease.
Benzatropine
Muscarinic antagonist.
Useful for when resting tremor is the predominant symptom.
