BB2 Revision2 Flashcards
Pharmacological management of Parkinson’s disease
Name two drugs that can combined with L-DOPA (aka levodopa) that means it doesn’t get metabolised to dopamine outside the BBB [2]
What is their MOA? [1]
L-DOPA (levodopa) & carbidopa or benserazide
carbidopa, benserazide are decaboxylase inhibitors: allows L-DOPA to pass BBB where it can then be converted to dopamine
Pharmacological management of Parkinson’s disease
Name 3 dopminergic agonists and describe their MOA
Dopamine agonists:
* ropinirole
* pramipexole
* rotigotine (in BB PBL; transdermal patch)
Dopamine agonists act directly on the dopamine receptors and mimic dopamine’s effect
Which of the following dopamine agonists can be used as a transdermal patch?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as a transdermal patch?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Why are dopamine agonists sometimes an advantage if a patient has difficulty swallowing? [1]
Dopamine agonists differ in their pharmacokinetics: longer acting drugs require fewer daily doses and this can be an advantage when there are swallowing difficulties
Pharmacological management of Parkinson’s disease
Name three drugs that are monoamine oxidase inhibitors [3]
Describe their MoA [1]
- rasagiline
- selegiline (in PBL)
- safinamide
MAO-B inhibitors stop Monoamine oxidase type B breaking down dopamine into DOPAC or homovanillic acid
What is the MoA of COMT inhibitors? [1]
Explain why [1]
Which drugs are they used in conjunction with? [1]
COMT is an enzyme involved in the breakdown of dopamine (DOPAC –> homovanillic acid) and hence may be used as an adjunct to levodopa therapy
Pharmacological management of Parkinson’s disease
Name 2 COMT inhibitors [2]
entacapone
tolcapone
Pharmacological management of Parkinson’s disease
Why are anticholinergic (antimuscarininc) compounds used to treat PD? [1]
Dopamine loss leads to hyperactivity of cholinergic cells
Pharmacological management of Parkinson’s disease
Name three anticholinergic compounds [3]
Which symtpom are they particularly good for treating? [1]
orphenadrine, procyclidine, trihexyphenidyl
Block tremors (as block muscarinic receptors on muscles) but also cause dry mouth and constipation
Pharmacological management of Parkinson’s disease
What is the MoA of Amantadine? [3]
inhibits dopamine reuptake, increases dopamine release, also weak antagonist at NMDA glutamate receptors
Pharmacological management of PD:
Other treatment approaches
Name two cell based approaches that can use to treat PD [2]
- Striatal graft of embryonic mesencephalic cells: intrastriatal transplant of foetal nigral cells
- Systemic administration of mesenchymal stem cells: Improvement following repeated intravenous injection of adipose tissue-derived cells
Surgical approaches in Parkinson’s disease
Describe the surgical approaches to PD treatment [4]
Electrode stimulation of the subthalamic nucleus
Thalamotomy
Pallidotomy
deep brain stimulation for people with advanced Parkinson’s disease whose symptoms are not adequately controlled by optimised pharmacological therapy
Name the gene that has associated changes causing Huntingdons disease [1]
What do codon / repeat sequence occurs due to this abnormal gene? [1]
Huntingtin gene
Repeats of glutamine (CAG)
Name the mechanisms underlying neurodegeneration of HD [7]
- Excitotoxicity
- Loss of neurotrophic factors
- Accumulation of aggregates of mutant huntingtin protein
- Dysregulation of gene transcription
- Increased oxidative stress
- Abnormalities in axonal transport
- Synaptic abnormalities
Pharmacological management of Huntington’s disease
Name two classes of drugs used to treat HD [2]
Vesicular amine transporter inhibitor (Decreases levels of dopamine in dopaminergic terminals)
Antidopaminergic (antipsychotic) drugs
Pharmacological management of Huntington’s disease
Name drugs for that used to treat HD that use following mechanisms:
- Vesicular amine transporter inhibitor [1]
- Antidopaminergic (antipsychotic) drugs [2]
- Vesicular amine transporter inhibitor: tetrabenazine
- Antidopaminergic (antipsychotic) drugs: haloperidol, olanzapine
Pharmacological management of Huntington’s disease
Name three antidepressant drugs used in the management of HD [3]
Antidepressant drugs: citalopram, fluoxetine, sertraline
Name an experimental non-pharmacological approach for treatment of HD [1]
Striatal fetal grafts
Motor control:
Motor control is a distributed process.
What are the two levels involved in motor control?
- Central representation of goals and planning of the more abstract components of the movement (what am i going to do / how am i going to do this?)
- Production of goal orientated movements (patterns of muscular activation)
The main brain areas involved in motor control:
Name the main areas of the brain involved in:
Decision making & movement planning [2]
Organisation of movement [2]
Movement execution [1]
Decision making & movement planning [2]
* Posterior parietal cortex
* Frontopolar cortex
Organisation of movement [2]
* Supplementory motor cortex
* Premotor cortex
Movement execution [1]
* Primary motor cortex
Brain areas involved decision making & movement planning:
Which area of the brain is where conscious intentions are formed and we become aware of motor movement? [1]
Name another key function of this area? [1]
The posterior parietal cortex
Also provides a representation of the body and how it is situated in space
Broadmann areas 39 & 40
What is the function of the pre-frontal cortex? [2]
Pre-front cortex controls executive function (allows us to use perceptions, knowledge & to bias / choose the from the selection of actions and thoughts from multiple possibilites)
This allows you to overide habitual responses
Pre-frontal cortex:
For successful completion of goal-oriented behaviour, we need to do completee three steps? [3]
- Develop a plan of action
- Monitor our actions
- Inhibit habitual response to obtain a goal (e.g. go for a run if trying to get fit instead of sofa)
Prefrontal cortex:
Dorsolateral prefrontal cortex
What is this region of the pre-frontal cortex involved with? [3]
Planning of goal-directed behaviours AND simulating the consequences of plans
Initiating, inhibiting and swtiching executive behaviour: input to the basal ganglia about stop / start
Involved with:
Problem-solving
Goal-driven attention
Planning
Decision making
Working memory
dorsolateral prefrontal cortex:
Lesions in Brodmann area 46 affects which functions? [1]
Attention and working memory: affects ability to inhibit a response to a stimulus
What is the role of the medial prefrontal cortex ?
Guide and monitor actions that are internally guided according to preferences and goals:
I.e. it modulates the degrees of cognitive control need to keep in behaviour in line with the goal
Prefrontal cortex
What is the role of the orbitofrontal cortex? [1]
Representation of value for rewards and punishers (what is good for you / bad for you)
Name the secondary motor areas involved in motor movement [2]
- The supplementary motor area (SMA)
- The premotor cortex
label A-C
A: primary motor cortex
B: supplementary motor area
C: premotor cortex
supplementory motor area:
Location:
Broadmann area? [1]
Lobe? [1]
Role? [2]
Location:
medial part of BA 6; frontal cortex
Role:
* Orgnaises actions that are internally guide according to preferences and goals: choosing objects
* Determines response threshold to initiate movement - the urgency of movement
* Response to start or stop a movement (interconnects to basal ganglia)
e.g which object to choose (in alignment with goals)
plan sequence of learned actions - e.g. playing piano
Premotor cortex:
What is the role of the premotor cortex? [1]
Where is the premotor cortex located? [1]
Lateral of area 6
Organises externally sensory guided actions (catching a ball)
Label the orange, purple, green and grey barts of the brain
Purple: premotor
orange: dorsolateral prefrontal
green: orbitofrontal
grey: FEF
Which region of the brain is responsible for this image? [1]
pre-motor cortex
How is the the somatosensory cortex involved in motor control?
40% of corticospinal and corticobulbar tract axons arise from somatosensory cortex; can modulate somatosensory input (e.g. supress nocicpetive pain)
Where does the corticospinal tract cross decussate in the body? [1]
On the way to the brainstem, which structure does the cortiospinal tract pass through? [1]
Decussates in upper spinal cord: C1-C5
Goes through the internal capsule on way to brainstem
Extrapyramidal tracts:
Desribe the path of the medial and lateral reticulospinal tracts [2]
Medial Reticulospinal Tract (Pontine): Descends ipsilaterally
Lateral Reticulospinal tracts (Medullary): Descends bilaterally
Extrapyramidal tracts:
Desribe the path of the medial and lateral reticulospinal tracts [2]
Medial Reticulospinal Tract (Pontine): Descends ipsilaterally
Lateral Reticulospinal tracts (Medullary): Descends bilaterally
Extrapyramidal tracts:
Describe the course of the lateral vestibulospinal tract [1]
Which type of muscles does it synapse onto? [1]
Fibres descend ipsilaterally though the anterior funiculus of the same side of the spinal cord, synapsing on the extensor antigravity motor neurons: help maintain upright and balanced posture.
Describe the function and path of the rubrospinal tract [2]
Function: Controls muscle tone in flexor muscle groups; Inhibits extensor tone
Path:
- Arises from the red nucleus in the brainstem
- crosses at medulla
- terminates primarily in the cervical and thoracic portions of the spinal cord
Path and function of tectospinal tract? [2]
Coordinates voluntary head and eye movements
Involved in both auditory and visual cues, it is primarily understood to orient our eyes and head towards both auditory and visual stimuli. For example, if you were sitting in a quiet room and all of a sudden heard a noise to your right, you would subconsciously turn your head in that direction and orient your eyes towards the direction of the sound, attempting to find the source.
Path:
Originates in the superior colliculus
Projects to the contralateral cervical spinal cord to terminate in Rexed laminae VI, VII, and VIII
