Pharmacology and Therapeutics - Jones Flashcards
What is an interictal?
The state between seziures
Some (abnormal spike) activity can be recorded in the brain
What is Epilepsy?
A sudden, excessive high frequency neuronal discharge (of millions at the same time) that is highly synchronous in the cerebral cortex
What % of epileptics are drug-refractory?
30%
What are the 2 ways that we can record the activity of the brain?
And what are the other 3 imaging techniques that can be used?
EEG and MEG
Imaging: PET, MRI and fMRI (done with an EEG)
What’s the difference between tonic-clonic, partial , simple and focal seziures?
Tonic Clonic –> Last for minutes
Partial –> Last for seconds
Simple –> No loss of consiousness
Focal –> Only part of the brain is involved, and often presents with a pre-aura
Which parts of this recording is the tonic part and which is the clonic?
Tonic = 2
Clonic = 3
What is the basic reason for seziures occuring?
And what are the 2 levels of this?
An imbalance between excitation and inhibition in the cortex
Intrinsic –> Ion channels
Ca2+/Na+ are depolarising (excitatory) whilst Cl- and K+ are hyperpolarising (inhibitory)
Network –> Synaptic Transmission
Which type of glutamate receptor starts seziures off?
AMPA
Name 4 ways in which seziures can be stopped naturally
K+ channel activation
Na+ channel inactivation
Glutamate receptor desensitisation
Glutamate depletion
How do Na+ channel blocking drugs (like phenytoin) work in the treatment of epilepsy?
Block the Na+ channel in its inactivated form, allowing occasional APs to form, but preventing consistant activation
How does Phenytoin(?) and ethosuximide function as anticonvulsants?
Block calcium channels directly
What is Levetiracetams mechanism of action?
Reduce vesicle fusion, reducing glutamate levels
What are the 3 ways of increasing GABA levels to prevent seziures?
Inhibit GABA transaminase
Block GABA reuptake
Enhance postsynaptic response by prolonging the channel open time
What are the 3 levels of motor control in the brain?
High –> Planning and strategy
Middle –> Tactics, preperation and direction
Low –> Execution
Explain the key structures that are involved in motor pathways in the brain
Brain Stem –> Processes sensory information from the cerebral cortex, basal ganglia and cerebellum. This information is then sent to the spinal cord
Cerebellum –> Takes information regarding motor co-ordination and correction from the cerebral cortex. Then sends this information to the brain stem
Thalamus –> Gets information from the spinal cord, cerebellum and basal ganglia. Then feeds this information to the cerebral cortex
What does the Cortico-Spinal Tract do?
Sends information from the motor cortex to the spinal cord (a lateral pathway)
Used in the voluntary control of movement
The vestobulospinal tract, tectrospinal tract and reticulospinal tract are all examples of what?
Ventro-medial motor pathways
What is key role of the basal ganglia?
And what is its main output?
Decision making, planning and execution
The Thalamus
Explain the direct and indirect pathways through the basal ganglia, as well as the role of the SNc
Direct –> The cortex stimulates the caudate and putamen, which inhibits GPi/SNr. The reduces the inhibition of the thalamus, meaning the cortex is stimulated more, and so there is more stimulation of the cortico-spinal tract
Indirect –> The cortex stimulates trhe caudate and putamen, which inhibits GPe. This reduces the inhibition of STN, increasing the stimulation of GPi/SNr. The increases the inhibition of the thalamus, and so reduces the stimulation of the cortex
SNc Modulation –> Part of the nigro-striatal pathway
D1 receptor activation (direct) will increase cortex stimulation
D2 receptor activation (indirect) will inhibit the cortex
What are the main symptoms of Parkinsons?
Akinseia (reduction/slowness of movements)
Rigidity
Tremor
Speech problems
Poor balance
Mental health problems –> due to the debilitating condition
What is the primary pathology for why parkinsons occurs?
And what is the outcome of this?
Loss of dopaminergic neurones from the SNc
Also degeneration of the nigro-striatal pathway
Loss of the SNc causes greater inhibition of GPe, reducing the stimulation of STN……increasing the stimulation of the GPI/SNr. The increases the inhibition of the thalamus, which reduces the stimulation of the cortex, and the cortico-spinal pathway…..reducing movement!!
What are the pharmacological ways of treating parkinsons?
Main aim is to improve the dopamine levels
COMT inhibitors (entacopone) and MAO inhibitors (selegiline) which both slow down the degredation of dopamine
L-Dopa (with peripheral DOPA-decarboxylase inhibitors like carbidopa) to increase dopamine levels in the brain by being converted to dopamine by DOPA-decarboxylase, but not in the periphery
In huntingtons disease, what declines first….cognition or motor programs?
And what are the key symptoms?
Cognition
Involunatary jerking (chorea)
Grimacing
Gait and balance problems
Swallowing and speech problems
Death around 10-20 years after diagnosis
What is the key pathology in huntingtons disease?
And what effect does this have?
Cell death in the caudate and putamen, with a preserved nigro-striatal pathway
Also a large genetic factor, with mutant huntigntin protein being key
There is no inhibition of GPe, so there is strong inhibiton of the STN, which reduces the amount of stimulation to the GPi/SNr. This reduces the inhibiton of the thalamus, causing a large stimulation of the cortex and so cortico-spinal pathway…which increase movement!!
Name 3 ways in which we can treat the symptoms of huntingtons disease pharmacologically?
Anti-spasmodics –> Baclofen
D2 antagonists –> Chlorpromazine
Caspase Inhibitors –> To prevent apoptosis (prevent rate of degeneration)
What is Cerebellar Dysfunction?
Degenetration of most cerebral pathways
This causes voluntary movement problems, as well as fine motor control, gait and co-ordination problems
What does the SNc do?
Activates D1 receptors
Inhibits D2 Receptors
Does this via the nigro-striatal pathway
Why does tourettes occur?
How what is often used to treat it?
Increased activity in the nigro-striatal pathway causing rapid motor responses
Treated with D2 receptor antagonists
How can we reduce ‘off-time’ in parkinsons medications?
Add in a MOA-B (selegiline) or COMT inhibitor (entacapone)
