- Name the neurotransmitters released by the corticostriatal and striatopallidal pathways. (1 mark)
Glutamate and GABA, respectively (1 mark).
- Describe the effects of D1 receptor activation on striatal efferent circuitry. (2 marks)
D1 receptor activation causes the activation of the direct pathway (½ mark)
by which the internal globus pallidus (GPi) is inhibited (½ mark).
This causes the disinhibition of the thalamus (½ mark)
and consequently the activation of the cortex (½ mark).
- What is alpha-synuclein, where is it found in the brain and what is its genetic link with Parkinson’s disease? (2 marks)
Alpha-synuclein is a protein found in Lewy bodies in neurons (½ mark).
Lewy bodies are a major histopathological feature of Parkinson’s disease (½ mark).
The gene for alpha-synuclein is the SNCA gene; mutations associated with this gene (e.g. PARK1/4) have been identified as a genetic risk factor for Parkinson’s disease (1 mark).
- List and briefly describe three long-term complications of levodopa (L-DOPA) therapy. (3 marks)
- Motor fluctuations: include the ‘on-off’ phenomenon in which sudden and dramatic fluctuations of motor performance occur; periods of normal mobility (on) followed by sudden ‘freezing’ (off). End of dose deterioration and delayed (or ‘no on’ - freezing) responses also occur.
- Dyskinesias: include choreiform movements (purposeless involuntary dance-like movements) and dystonias (sustained intense muscle contractions).
- Non-motor complications: tingling, pain, akathisia, and autonomic dysfunction.
- Neuro-psychiatric problems: hallucinations, delirium, mood changes, sleep disturbance and nightmares.
- What is rotigotine and what is its route of administration? (2 marks)
Rotigotine is a dopamine receptor agonist (non-selective agonist), with affinity for both the D1 family and D2 family receptors (1 mark). It is applied transdermally as a patch (1 mark).
Name a drug for PD that can be continously provided over a 24 hr period [1]
TN
rotigotine: due to transdermal patch
Which drugs are best used to treat milder PD symptoms? [5]
TN
selegiline (an MAOB inhibitor) or the newer drug rasagiline
amantadine: causes release of dopamine
anticholinergic drugs (e.g. orphenadrine, procyclidine, trihexyphenidyl)
These drugs are less efficacious than L-DOPA, and are mainly used as adjunctive therapy
Which vitamin may be useful for treating PD? [1]
Why? [1]
TN
Vitamin E is an anti-oxidant, and there is convincing evidence that Parkinson’s disease is associated with increased oxidative stress in the nervous system
DBS of which region may be useful to treat PD? [1]
TN
deep brain stimulation of the subthalamic nucleus
Which hypothesis explains many pro-dromal non-motor symptoms of PD? [1]
Braak hypothesis:
* Parkinson’s disease start many years before the clinical diagnosis is made, and involve a particular propagation of neurodegeneration
What is the Hz of PD tremor? [1]
Tremor
* most marked at rest, 3-5 Hz
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural
hypotension are also seen in some patients
This applies to which drug class? [1]
Dopamine agonists
Decribe the differences between the following?
* individual CBT
* individual behavioural activation (BA
* counselling
* short-term psychodynamic psychotherapy (STPP)
* interpersonal psychotherapy (IPT)
Which drug class is considered first-line treatment for the majority of patients with depression? [1]
Which two drugs are most commonly prescribed? [2]
SSRIs
Citalopram; Fluoxetine
Which drug is useful post myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants? [1]
sertraline
What additional care should be given after prescribing a SSRI? [1]
- patients should be counselled to be vigilant for increased anxiety and agitation after starting a SSRI: suicide ideation common
citalopram and escitalopram are associated with what important AE? [1]
associated with dose-dependent QT interval prolongation
SSRIs should not be combined with which drug classes to increase the risk of seratonin syndrome? [2]
triptans - increased risk of serotonin syndrome
* monoamine oxidase inhibitors (MAOIs) - increased risk of serotonin syndrome
When stopping a SSRI the dose should be gradually reduced over a [] week period (this is not necessary with fluoxetine).
Which SSRI has a higher risk of discontinuation syndrome? [1]
When stopping a SSRI the dose should be gradually reduced over a 4 week period (this is not necessary with fluoxetine).
Paroxetine has a higher incidence of discontinuation symptoms.
Name some symptoms of SSRI discontinuation syndrome
increased mood change
* restlessness
* difficulty sleeping
* unsteadiness
* sweating
gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
* paraesthesia
Descibe the MoA of CBT [2]
The aim of CBT is to help you explore and change how you think about your life, and free yourself from unhelpful patterns of behaviour.
You set goals with your therapist and may carry out tasks between sessions
Describe the MoA of Guided self-help
With guided self-help you work through a CBT-based workbook or computer course with the support of a therapist.
The therapist works with you to understand your problems and make positive changes in your life.
Guided self-help aims to give you helpful tools and techniques that you can carry on using after the
course has finished.
During the course your therapist will support you with face-to-face, online or phone appointments.
Describe MoA of Interpersonal therapy (IPT)
IPT is a talking treatment that helps people with depression identify and address problems in their
relationships with family, partners and friends.
The idea is that poor relationships with people in your life can leave you feeling depressed.
Depression can in turn make your relationships with other people worse.
Describe the MoA of Behavioural activation
Behavioural activation is a talking therapy that aims to help people with depression take simple,
practical steps towards enjoying life again.
The aim is to give you the motivation to make small, positive changes in your life.
