Parkinson's disease 1/2 Flashcards
what occurs in the catecholamie synthesis?
tyrosin to L-dopa by ttrosine hydroxylase
L-dopa to dopamine by aromatic L-amino acid decarbosylase
DA to NA by dopamine B-hydroxylase
NA to AD by phenyl ethanolamine N-methyltransferase
how common is PD in the UK?
Parkinson’s Disease (PD) second most common neurodegenerative disorder in UK after Alzheimer’sdisease.
how does PD occur?
Degeneration of dopamine secreting nerve cells although other neurons and neurotransmitter maybe involved
how is PD most commonly presented?
Patients have severe attack of tremors that affect one hand and then spread to the leg on the same side and then to the limbs
what would be present in neurons of a PD patient?
resence of cytoplasmicinclusions called Lewy bodies in some survivingneurons
what causes the degeneration of neurons in PD?
Excess of free radicals causes the degeneration of the neurons
what are the motor symptoms of PD?
T – Tremor: Involuntary shaking, trembling caused by muscles alternately contracting and relaxing at a rapid pace R – Rigidity: raised tone, maybe asymmetrical or limited to certain muscle groups A- Akinesia: Slowness of movement P - Postural instability: Balance problems, seen in cases of classic Parkinson’s
what are the non-motar symptoms of PD?
• Neuropsychiatric – Anxiety disorders, apathy, depression, psychosis and visual hallucinations, dementia. • Sleep disturbances – Excessive daytime sleepiness • Autonomic disturbances- Constipation, urinary dysfunction, sexual dysfunction, postural hypotension, weight loss, dysphagia, excessive sweating, excessive salivation • Sensory disturbance - Pain and olfactory dysfunction
what is bradykineseia?
abnormal slowness of movement
what is akinesia?
absence or loss of the power of voluntary movement
what are the risk factors for PD?
• Non – smokers and low caffeine drinkers are at
increased risk.
• Genetic mutations particularly autosomal
dominant mutations in gene LRRK-2 (5% of UK PD
patients).
• Mutations in parkin gene (autosomal recessive
type) can also cause PD
• Neuroleptic drugs can lead to symptoms of
Parkinson’s.
• Antiemetics such as Prochloperazine &
Metoclopramide can also cause Parkinson’s
disease.
where is DA produced?
basal ganglia
what is the role of the basal ganglia?
to orchestrate the
performance of well-learnt, voluntary and semi-
automatic motor skills and movement sequences.
what effects does DA have on the basal ganglia?
Dopamine promotes the functions of basal ganglia
and also plays a major part in various cognitive tasks
such as maintaining attention, switching the focus of
attention, mood, problem solving, decision making
and visual perception.
where are DA producing neurones located?
located in the
substantial nigra within basal ganglia.
how does formation of lewy bodies occur?
Progressive degeneration in dopamine producing
neurons leads to formation of Lewy bodies – the
characteristic hallmark used for the diagnosis of
Parkinson’s disease.
what is the characteristic hallmark used for the diagnosis of PD?
lewy bodies
where do lewy bodies get deposited in?
the dopamine
producing neurons and consequently such neurones
produce little or no dopamine.
when are clinical signs of the disease evident?
when around
80% of dopamine producing neurons are lost.
what causes PD?
• Dopaminergic neurons in substantia nigra and corpus
striatum (nigrostriatal DA-ergic tract) are destroyed
• Nigrostriatal dopaminergic tract - part of the
extrapyramidal system, responsible for motor control
• 80% of dopaminergic neurons are damaged, the
symptoms of Parkinson disease appear.
• The striatum, is also rich in excitatory cholinergic
neurons that counteract the action of dopamine.
• This is the dopamine-acetylcholine balance
• The dopaminergic system inhibits the ACh system
what is step 1 in diagnosing PD?
Step 1: Diagnosis of Parkinsonian Syndrome Bradykinesia plus one of the following - Rest tremor - Rigidity - Postural instability
what is step 2 in diagnosing PD?
Step 2: Exclusion criteria including History of - Repeated strokes - Neuroleptic medications use - Head injury - Definite encephalitis Presence of atypical features such as - Early falls - Supranuclear gaze palsy - Ataxia and cerebellar features - Early autonomic features - Early cognitive decline - Poor response to L-dopa
what is step3 in diagnosing PD?
Step 3 : Supportive clinical features (at least 3 required) - Unilateral onset - Rest tremor - Evidence of progression - Persistent asymmetry - Excellent response to L-dopa - L-dopa induced dyskinesias - L-dopa response for 5+ years - Clinical course of 10+ years
what is diagnosis of PD usually based on?
TRAP- motor symptoms
what should happen if PD is suspected?
patient should be referred to a
neurologist or geriatrician with specialist PD interest
for a definite diagnosis.
how can an MRI/CT scan help with PD?
may help in the diagnosis
what drugs are used in PD to restore the dopamine levels in nigro-stratal dopaminergic tract?
Levodopa (L-dopa) and carbidopa/benserazide Dopamine agonists MAO-B inhibitors COMT inhibitors Miscellaneous (Amantadine)
what drugs restore the dopamine-acetylcholine balance?
antimuscarinic
what is the most effective medicine for PD?
levodopa
what are the standard release preparations available for levodopa?
- levodopa/carbidopa (Sinemet)
- levodopa/benserazide (Madopar)
what are the prolonged release prep for levodopa?
- levodopa/carbiopa (Sinemet CR)
- levodopa/benserazide (Madopar CR)
what is the metabolic precursor of DA?
levodopa
what do the therapeutic and adverse effects of levodopa result from?
result from
decarboxylation to DA
