Neurology Flashcards
What is used in idiopathic Parkinson’s disease to improve motor symptoms?
Levodopa
Outline the pathology of idiopathic Parkinson’s disease
- Neurodegeneration
- Lewy bodies
- Loss of pigment due to increased turnover
- Reduced dopamine
Clinical features of Parkinsonism
Tremor
Rigidity
Brradykinesia
Postural instability
Diagnosis of idiopathic Parkinson’s disease
- clinical features
- exclude other causes of Parkinsonism
- response to levodopa
- structural neuro imaging is normal
- must have bradykinesia
What is idiopathic Parkinson’s disease?
Progressive neurodegenerative disorder due to loss of substantia nigra dopamine neurones
At what point of loss of pigment in idiopathic Parkinson’s disease do symptoms present?
> 50% loss
Non motor manifestations of idiopathic Parkinson’s disease
- mood changes
- hallucinations
- sleep disorder
- fatigue
- urinary symptoms
- hypotension
Describe Parkinsonian tremor
Low frequency
Pillrolling
At rest
Stops with movement
Describe Parkinsonian rigidity
Lead pipe
Tension all the way through flexion
Describe Parkinsonian gait
- short shuffling steps
- struggle to initiate + stop
- turning on block
- asymmetric arm swing
What enzyme converts levodopa to dopamine?
Dopa decarboxylase
Outline catecholamines synthesis
L tyrosine > levodopa > dopamine > noradrenaline > adrenaline
Why is levodopa used instead of dopamine to treat idiopathic Parkinson’s disease?
Levodopa crosses the blood brain barrier but dopamine cannot
Pharmacokinetics of levodopa
- oral administration
- absorbed by active transport
- t1/2 2 hours
- 90% inactivated in intestinal wall
How is levodopa converted to dopamine?
- Cross BBB
- Taken up by axons within substantia nigra
- Converted into dopamine in the cell
- Catalysed by dopa decarboxylase
Describe the formulation of levodopa
- used in combination with peripheral dopa decarboxylase inhibiotr
- co-careldopa: levodopa + carbidopa
- co-beneldopa: levodopa + benserazide
- tablet only P.O.
Why is levodopa given in combination with peripheral dopa decarboxylase inhibitor?
- Reduces conversion in peripheral tissue
- Reduces dose required
- Reduces side effects
- Increased levodopa reaching brain
Advantages + disadvantages of levodopa
Advantages:
- high efficacy
- low side effects
.
Disadvantages:
- loss of efficacy long term due to degeneration of axons
- needs enzyme conversion
- motor complications long term
Side effects of levodopa
- Nausea + anorexia
- hypotension
- psychosis (schizophrenia like effects)
- hallucination
- tachycardia
Motor complications of long term levodopa
- wearing off
- dyskinesias
- dystonia
- freezing
Important drug drug interactions with levodopa
- pyridoxine increased peripheral breakdown
- monoamine oxidase inhibitors increase risk of hypertensive crisis
- antipsychotic drugs block dopamine receptors
What drugs are used in treatment of idiopathic Parkinson’s disease
- levodopa
- levodopa with COMT inhibitor
- dopamine receptor agonists
- anticholinergics
- amantadine
Why do COMT inhibitor have no therapeutic effect alone?
Do not cross BBB
What is stalevo?
Combination tablets of COMT inhibitor, levodopa + peripheral dopa decarboxylase inhibitor
Mechanism of action of COMT inhibitors
- Reduces peripheral breakdwon of levodopa to 3-O-methyldopa by COMT
- 3-O-methydopa competes with levodopa active transport into CNS
- prolongs motor response to levodopa (reduces symptoms of wearing off)
Examples of COMT inhibitors
Entacapone
Opicapone
Examples of dopamine receptors agonists + their administration
- non ergot: ropinirole + pramipexole
- patch: rotigotine
- s.c.: apomorphine
Advantages + disadvantages of dopamine receptor agonists
advantages:
- direct acting
- less dyskinesia/motor complications
- possible neuroprotection
.
disadvantages:
- less efficacy than levodopa
- impulse control disorders
- more psychiatric side effects
- expensive
Examples of impulse control disorders
- pathological gambling
- hypersexulaltiy
- compulsive shopping
- desire to increase dose
- punding
What is punding?
Compulsive performance of repetitive, mechanical tasks such as collecting + sorting
Side effects of dopamine receptor agonists
- sedation
- hallucinations
- confusion
- nausea
- hypotension
What is used in patients with severe motor fluctuations
S.c. Apomorphine bolus
What is the action of monoamine oxidase B?
Metabolises dopamine
What is the mechanism of action of monoamine oxidase B inhibitors?
Inhibits monoamine oxidase B > reduces metabolism of dopamine
Examples of monoamine oxidases B inhibitors
Selegiline
Rasagaline
Safinamide
Advantages + disadvantages of anticholinergics in IPD treatment
advantages:
- treat tremor
- not acting via dopamine system
.
disadvantages:
- no effect on bradykinesia
- confusion + drowsiness
Why may meds be missed in hospital admissions?
- confused patients
- meds not known
- delays in writing up drug
- delays in acquiring drug on ward
- set times for drug round
Consequences of missed Parkinson’s disease meds on hospital admission
- worsening symptoms
- increased fall risk
- dopamine agonist withdrawal syndrome
Symptoms of dopmaine agonist withdrawal syndrome
- agitation
- panic
- anxiety
- depression
- fatigue
- hypotension
Solutions of missed Parkinson’s disease meds due to hosptial admission
- education for ward staff
- prioritise prescription, acquisition + administration of meds
- self administration if appropriate
- rotigotine patches or s.c. Apomorphine if oral cannot be taken
- incident report for missed dose
What is fatiguability?
A muscle that is in use gets weaker as you use it
Strengthens with rest
Presentation of myasthenia gravis
- fatiguability
- dysphagia, dysphonia, dysarthria
- fluctuating weakness
- ptosis
- double vision
Management of myasthenia gravis
Acetylcholinesterase inhibitors
- enhances neuromuscular transmission
Examples of acteylcholinesterase inhibitors
Pyridostigmine
Neostigmine
What is the onset + duration of pyridostigmine?
30min onset
3-6hour duration
Side effects of pyridostigmine
- miosis
- SSLUDGE syndrome:
- salivation
- sweating
- L acrimation
- urinary incontience
- diarrhoea
- GI upset
- emesis
How does the onset of pyridostigmine affect its administration?
Given 40-60 mins before meals to optimise swallow
