Parkinson's Flashcards
Bradykinesia, Muscle Rigidity and Tremor are examples of what type of Symptom in Parkinson’s?
Motor
What are the examples of non-motor symptoms in Parkinson’s?
Depression/anxiety, Fatigue, Cognitive impairment/dementia, sleep disturbance, constipation, hyposmia, sialorrhoea, excessive sweating, urinary/bladder problems, pain, hypotension
In the Dopaminergic pathway, Motor control is what system?
Nigrostriatal
In the Dopaminergic pathways, Behavioural effects are controlled by what system?
Mesolimbic and Mesocortical systems
In the Dopaminergic pathways, Endocrine control is controlled by what system?
Tuberohypophyseal system
What is Bradykinesia?
‘Slowness of voluntary movement’
A Parkinson’s patient which is presenting with asymmetrical, mask-like face/limited expressions with limited blinking, a soft or monotone voice, small handwriting, difficulty performing fine motor actions and a shuffling gait is having what symptom of Parkinson’s?
Motor Symptoms - Bradykinesia
What Rigidity motor symptoms could be seen in a Parkinson’s patient?
-Increased muscle tension
-Stooping posture
-Rigidity affecting balance increasing the risk of falls *due to slower reactions = -Bradykinesia
-Muscle pain
-Affects elbow and knee
Do all Parkinson’s patients have a tremor?
No!
There are many drugs which can cause a Tremor, what ones can cause a Intention tremor?
Lithium, Salbutamol, Salmeterol, Ethanol, Epinephrine, Tacrolimus, Ciclosporin
What drugs can cause a Resting Tremor?
Co-trimoxazole, SSRI’s, Lithium, Valproic acid, Metoclopramide, Haloperidol, Cinnarizine,
What intrinsic causes of Parkinson’s are there?
Genetic
*lewy body *parkin gene *A-synuclein point mutations
Age
What groups of prescription drugs can cause Parkinson’s?
Antipsychotics & Antiemetics
What can cause lewy body formation?
A-Synuclein
What can a-Synuclein cause?
DNA damage / inherited, which is autosomal dominant = early onset
How does pre-synaptic protein a-Synuclein make Lewy bodies?
1) Brain plascity and misfolded proteins are made which aggregate in the neuron,
2) Damages cellular components
3) Lewy Bodies are formed causing neuronal misfunction which results in cell death.
4) Dementia
A genetic cause of Parkinson’s is ‘Parkin’ what is this?
A neuroprotective protein, made from a-synuclein and cellular damage. Loss of this causes cell damage and cell death.
What gene encodes for Parkin?
PARK2 Gene
What anti-emetics can cause Parkinson’s?
Metoclopramide, Prochlorperazine
What effect do recreational drugs have on inducing Parkinson’s?
MPTP which is found in synthetic Heroin,
-This metabolite kills dopaminergic neurons in substantia nigra Sudden,
=Irreversible Parkinsonism
Are Antipsychotics that cause Parkinson’s reversible?
Yes
What drugs deplete monoamines from pre-synaptic storage, reducing Dopamine release?
Reserpine, Tetrabenazine
What viral illness can cause Parkinson’s?
Encephalitis lethargica epidemic, patients end up in a state of permanent rigidity, = some short term relief from L-DOPA
What is first line therapy for motor symptoms of Parkinson’s disease when QoL is affected?
QoL affected - Levodopa
If quality of life isn’t affected in a patient with Parkinson’s what medications should be offered?
Dopamine agonist and Monoamine inhibitor
When is add on therapy given for motor symptoms of Parkinson’s disease?
1) First line is optimised
2) When dyskinesia or motor fluctuations develop
WHAT is add on therapy for Motor symptoms of Parkinson’s disease?
1) Dopamine agonists, monoamine oxidase B inhibitors or catechol-O-methyl transferase inhibitors as an adjunct to levodopa
If Dyskinesia is not adequately managed by modifying existing therapy what drug should be considered?
Amantadine
When is Levodopa started?
Individualised patient plan, different for all.
-80+ start ASAP
-Young onset start later on…
What are the THREE unwanted effects of Levodopa?
1) Dyskinesia
2) Fluctuations in clinical state
3) Acute side effects
What are incorporated with Levodopa?
Dopadecarboxylase Inhibitors
What are examples of Dopadecarboxylase inhibitors?
-Carbidopa
-Benserazide
Why is Levodopa a combined medication?
As levodopa is metabolised in the periphery and the brain therefore, these peripheral inhibitors prevent the majority of it being metabolised in the periphery and more can cross the BBB and more dopamine can be active in the brain.
What combination is Sinemet?
Carbidopa + Levodopa
What combination is Madopar?
Benserazide + Levodopa
What are COMT Inhibitors?
Entacapone and Tolcapone
Can COMT inhibitors be used with Levodopa products?
YES! ADD ON and in Combination
What COMT inhibitor can cause liver toxicity?
Tolcapone
What does a COMT inhibitor do?
Potentiate the effects of Levodopa - increases Levodopa effect
What are Brand examples of Co-careldopa + Entacapone
Stanek, Stalevo, Sastravi
What side effects should a patient be counselled on when taking Entacapone?
Red/Orange urine, Loose stool - which should settle over time.
What is the MAX dose of Levodopa?
800mg
What do small does of Levodopa at increased frequencies do?
Reduce peaks and troughs and dyskinesia
How and why should you wait before eating after taking Levodopa?
Proteins inhibit absorption, wait 30-60 mins- can have a low protein snack such as a cracker
Should Levodopa be prescribed by brand?
YES
How many hours does an iron supplement need to be taken if the patient is on Levodopa?
2-3 hour gap
Examples of Non-ergot Dopamine Receptor Agonists?
-Ropinirole
-Rotigotine
-Pramipexole
Examples of Ergot derived Dopamine Receptor Agonists?
Bromocriptine
Cabergoline
Lisuride
Pergolide
What type of Dopamine Receptor Agonists are best tolerated?
Non-ergot derived
What type of Dopamine Receptor Agonists can cause fibrotic lungs/heart valve?
Ergot derived
When are Ergot Derived Dopamine Receptor Agonists used?
If inadequate response to non-ergot derived
Dopamine Agonists can increase the risk of Impulse Control Disorders, Why is this?
Function of Dopamine is reward pathways, behaviour, attention and concentration.
What are examples of Monoamine Oxidase B inhibitors?
Selegeline and Rasagiline
What does Monoamine oxidase B inhibitors do?
Monoamine oxidase B metabolises dopamine therefore inhibiting this, increases Dopamine concentration
Do Monoamine oxidase B inhibitors interact with tyramine?
NO as they are selective for B type receptors
What are some common side effects to Monoamine oxidase B inhibitors?
Nausea, postural hypotension, dyskinesia, confusion in the elderly
What does Amantadine do?
Increases dopamine levels
What can possibly prolong effectiveness of Amantadine?
Slowly withdrawing and reintroducing the drug
Can Amantadine cause, psychological effects, sleep disturbances, GI effects, Hypotension and palpitations?
YES
Which drug shows no evidence in improving motor symptoms?
Amantadine
What drug has no evidence of improving quality of life in Parkinson’s disease?
Amantadine
Which drug for Parkinson’s disease has the fewest side effects?
MOA-B inhibitors
What Parkinson’s drug has a lower risk of causing Hallucinations?
MOA-B inhibitors and COMT inhibitors
What Parkinson’s drug has a higher risk of causing Hallucinations?
Dopamine Receptor Agonists
What can happen if a patient with Parkinson’s misses a dose?
-Acute Akinesia (unable to initiate movement)
-More physically dependent on others
-Loss of ability to swallow increasing risk of aspiration
-Increased risk of falls
-Neuroleptic-like malignant syndrome (V.RARE)
Symptoms of Neuroleptic-like malignant syndrome (V.RARE!!!)
Fever, marked rigidity, altered consciousness, leucocytosis, elevated creatine kinase.
What causes Neuroleptic-like malignant syndrome?
Sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agent or from blockage of dopamine receptors
Who is more likely to get Neuroleptic-like malignant syndrome?
Severe PD symptoms on high doses of levodopa
What can be given to a patient suffering from Depression in Parkinson’s disease?
Normal 1st line SSRI!
What can be given to a patient suffering from Dementia in Parkinson’s disease?
Rivastigmine or off label use of Donepezil and Galantamine
What can be given to a patient suffering from confusion and hallucinations in Parkinson’s disease?
1st line - Quetiapine
2nd line - Clozapine
What can be given to a patient suffering from Impusle control and psychotic symptoms in Parkinson’s disease?
Optimise drug therapy
What is the first line treatment for a Patient with Parkinson’s suffering from Constipation?
Stimulant + Softener
What is the first line treatment for a Patient with Parkinson’s suffering from Postural hypotension?
1st line - Midodrine / fludrocortisone
What is the first line treatment for a Patient with Parkinson’s suffering from Dysphagia?
Medicines optimisation
What is the first line treatment for a Patient with Parkinson’s suffering from Salvation/drooling?
Glycopyrronium
What is the first line treatment for a Patient with Parkinson’s suffering from Bladder Dysfunction?
Anti-muscarinic
What is the first line treatment for a Patient with Parkinson’s suffering from Sexual Dysfunction?
PDE5 Inhibitors - Sildenafil
What is the first line treatment for a Patient with Parkinson’s suffering from Nausea and Vomiting?
1st line - Domperidone
Consider Cyclizine or Ondansetron
What is the first line treatment for a Patient with Parkinson’s suffering from Pain?
Follow pain ladder, Consider side effects, Physiotherapy
What is the first line treatment for a Patient with Parkinson’s suffering from Sleep disturbances?
Sedatives BUT can increase falls risk, PRN only
What drugs is Vigilance required?
Antihistamines, Antidepressants and Antipsychotics
When should a Parkinson’s patient’s medications be reviewed?
Every 6-12 months Specialist only
What should be on the labels of Parkinson patients medications?
Timings of when to take
What OTC medications should be avoided in a patient in Parkinson’s?
-Sympathomimetics: Pseudoephedrine + MOA-B inhibitors
-Antihistamines
Can Calcium Channel Blockers be used in patients with Parkinson’s disease?
YES! - Monitor as low BP is a common issue
Parkinson patients have an increased risk of Osteoporosis, therefore what should they be recommended?
Cholecalciferol
What type of D-like receptor acts via Gas to increase cAMP. PKA phosphorylates DARPP-32 which inhibits protein phosphatase-1?
D1-Like
What type of D-like receptor acts via Gai/o to decrease cAMP. The By subunits open K channels and inhibit voltage-gated Ca2+ channels?
D2-like
What D channel is inhibitory?
D2
What D channel is Excitatory?
D1
D1 and D5 are?
D1-like
D2, D3 and D4 are?
D2-like
What is the Dopamine function?
Acts on areas of the brain to give feelings of pleasure, satisfaction and motivation; memory, mood, sleep, learning, concentration and movement
What when binds to Dopamine can agonise a response? ‘Agonists’
Dopamine, Bromocriptine, Apomorphine, Cabergoline, Pergolide, Pramipexole, Ropinirole, Ariprazole
What when binds to Dopamine can STOP a response? ‘Antagonists’
Haloperidol, Sulpiride, Domperidone, Metoclopramide
What pathway accounts for 75% of DA in the brain, cell bodies in the substantia nigra protein the striatum, Controls movement and is of significance to Parkinson’s disease?
Nigrostriatal
What pathway?
VTA to limbic areas, notably the nucleus accumben’s, hippocampus and amygdala
-Plays a part in the behavioural and reward pathways, is of significance to Schizophrenia (+ve symptoms)?
Mesolimbic
What pathway? VTA to frontal cortex, cognition and thought, and plays a part in the negative symptoms and Schizophrenia?
Mesocortical
What pathway? Hypothalamus to the pituitary, controls hormone secretion and DA inhibits the prolactin secretion = S/E of drugs @ dopamine receptors.
Tuberohypophyseal
What type of receptors are most abundant and expressed at high density in the nigrostriatal, mesolimbic and mesocortical pathways?
D1 receptors
What receptor is most expressed in the CNS
D1
What type of receptors are at there highest density in the nigrostriatal, mesolimbic and tuberohypophyseal pathways, and also are in the CTZ medulla?
D2 receptors
What receptor is only really expressed in the limbic system?
D5
What receptor is widely expressed, and expressed in the tuberohypophyseal?
D2
What receptor is restricted / has week expression?
D3
What receptor is expressed in various places and has lower expression?
D4
Where is vomiting triggered?
Chemoreceptor trigger zone (CTZ)
Loss of dopaminergic neurons in the nigrostriatal pathway, is known of what disease?
Parkinson’s
What does the direct pathway do in the Nigrostriatal pathway?
Enables movement
What does the indirect pathway do in the Nigrostriatal pathway?
Inhibits movement
Where are Cholinergic interneurons abundant?
Striatum
What does Dopamine inhibit in the striatum?
Inhibits ACh release
A lack of dopamine in parkinson’s leaves ACh unopposed causing what?
Hyperactivity of cholinergic synapses
What does the release of ACh do?
Initiate movement
A decrease in dopamine means an increase in ACh, what does this cause?
Hyperactivity of cholinergic synapse = Tremor
What are intracellular aggregations of a-synucein found in neuronal cells known as?
Lewy bodies
What is A-synuclein involved in?
Exocytosis of synaptic vesicles and vesicle recycling
What causes plaque formation?
Misfolding
Plaque formation is usually removed via proteasomal pathways, this is decreased in PD’s, what does this cause?
Accumulation = Lewy bodies
What does a mutation of a-synuclein cause?
Early onset PD
As dopaminergic neurons require a lot of energy for their function what does that mean they require a lot of within their cell’s?
Mitochondria
Chemicals that induce PD cause stress and dysfunction to what, which is thought to play a role in causing PD?
Mitochondrial
What genes when mutated can cause PD?
Parkin and PINK1
What can lead to the death of dopaminergic neurons?
Mitochondrial damage
What will try to help with neuroinflammation?
Microglia
What neurotransitter is most associated with the pathophysiology of parkinson’s disease?
Dopamine
VMAT takes dopamine into synaptic vesicles in exchange for what ion?
H+
What pathways are dopamine pathways?
Mesocortical, Mesolimbic, Nigrostriatal, Tuberohypophyseal
What is the pharmacological target of carbidopa?
DOPA decarboxylase
What of the following is the pharmacological target of pramipexole?
D2-like receptors
What drug is used for daytime sleepiness and sudden onset of sleep in Parkinson’s?
Modafinil
What drug is used for Nocturnal Akinesia in parkinsons?
1st - Levodopa or Dopamine agonists
2nd - Rotigotine
What drug is used for Postural Hypotension in parkinsons?
1st) Are any drugs they are taking causing it
2) Midodrine hydrochloride or Fludrocortisone
What drug is used for rapid eye movement, sleep behaviour in parkinsons?
Clonazepam and Melatonin
If a patient with parkinsons is experiencing hallucinations or delusions, and has no cognitive impairment what should be offered?
1) Quetiapine
2) Clozapine
What can be given for a patient who has excessive drooling in parkinsons?
1) Glycopyrronium bromide
2) Botulinmum toxin type A
If a patient with parkinsons gets dementia what should be given?
Mild-mod = AChEi
