BB Flashcards
Genes Associated with Parkinson’s Disease
SNCA - Lewy Bodies
LRRK2 - most common (type of kinase)
Dopaminergic Pathways
o Mesocortical.
o Nigostriatal.
o Mesolimbic.
Dopaminergic Agonists:
Rotigotine: agonists which can be used as transdermal patch
Apomorphine: can be used as an infusion
MAOb Inhibitors
Rasagiline
Selegiline
Anticholinergic Compounds
Orphenadrine
Procyclidine
Amantadine
inhibits dopamine reuptake, increases dopamine release.
COMT Inhibitors
entacapone
tolcapone
Huntington’s Disease
Autosomal dominant disease
Changes in gene coding protein huntingtin on chromosome 4
Major loss of GABA-ergic striatal neurons and cortical atrophy
Parkinson’s Disease pathology
Loss of Dopaminergic cells in substantia nigra
Huntington’s Disease Treatment
Tetrabenazine: inhibitor of vesicular amine transporter (delete presynaptic dopamine -> less chorea)
Haloperidol, Olanzapine: antidopaminergic/antipsychotic drugs
Imipramine, Amitriptyline: antidepressant drugs.
Lenticulostriate arteries
Proximal part of MCA blood supply to the basal ganglia
Clasp-Knife Reflex
Resistance to arm extension until sudden stoppage of resistance
Particularly characteristic of chronic cerebral motor lesions.
Medulloblastoma
Most common malignant CNS tumour in children (tumour in 4th ventricle).
Nociceptors receptor proteins
TRPV1/2 open at high temperatures
TRPM8 open at very low temperatures.
ASIC3 is particularly present in skeletal and cardiac muscle: acid sensing- detect pH change with ischaemia.
Anterior vs Lateral spinothalamic tract in pain
AST moves arm.
LST causes response (i.e. to say “that hurts!”).
Anterior spinothalamic tract
These decussate to travel into the AST.
Innervate
a. Ventral posterior lateral, medial nuclei (VPL, VPM) of the thalamus –> Project to the primary somatosensory cortex (SI)
a) Localisation and physical intensity of the stimulus.
b. Ventral posterior inferior nuclei of the thalamus.
c. Central lateral (CL) of the thalamus –> Project to the anterior cingulate cortex.
a) Emotion/motivation)
CL –> Project to the prefrontal cortex and striatum.
a) Sites for cognitive function/strategy.
d. Somatosensory thalamus –> Project to the secondary somatosensory cortex.
Lateral spinothalamic tract
Mainly C fibres but also some alpha delta fibres innervate projection neurons in lamina I
- These decussate to travel into the LST.
- The innervate more posterior/medial parts of the thalamus.
a. Mediodorsal Nucleus (ventrocaudal) i.e. MDvc –> Project to the anterior cingulate cortex (ACC)
b. Posterior Thalamus (Posterior Nucleus and Ventral Medial Nucleus) –> Project to the anterior or rostral insula - Emotion, quality (i.e. pain), autonomic integration)
Prostaglandin synthesis
Phospholipase A2 releases Arachidonic Acid (AA) from cell membranes (due to inflammatory mediators)
COX1 and COX 2 use AA as a substrate for PG synthesis
COX-1 is normally present, COX-2 induced during inflammation
Circuitry of Cognitive and Emotional Control of Pain
Intensity: superior parietal lobe –> insula –> amygdala path (attention control) –> PAG.
Unpleasantness: ACC –> PCC –> PAG
Morphine Mechanism
Decreased excitability and decreased release of neurotransmitters.
o Due to activation of K+ conductance and decreased Ca2+ conductance.
NSAIDs (COX-2 inhibition)
Aspirin:
COX-1 and COX-2 inhibitor (also anti-inflammatory)
Ibuprofen, diclofenac, ketoprofen:
COX1/COX2 and additional mechanisms
Rofecoxib: selective COX-2 inhibitors.
Anticonvulsant Drugs (non-opioid)
Carbamazepine (acts on sodium channels)
Sodium Valproate (acts on sodium channels).
Pregabalin (acts on alpha2delta subunit)
Tricyclic Antidepressants (non-opioid)
Amitriptyline (inhibit reuptake of amines, block Na+ and Ca2+ channels).
Calcium channel ligands
gabapentin
pregabalin
verapamil
Opioid agonists
Tramadol
Medication that blocks sodium channels
lignocaine
prilocaine
Chandelier cells
Special population of interneurons which are GABAergic cells
o Control the activity of cortical pyramidal cells by synapsing on the axonal initial segment.
The loss of inhibitory CC increases the risk of abnormal excitatory activity
Phenytoin
stabilises the inactivated state of channels
DO NOT USE IN ABSENCE SEIZURES.
Carbamazepine
stabilises the inactivated state of channels.
DO NOT USE IN ABSENCE SEIZURES.
Sodium Valproate
Used in all types of seizures
Lamotrigine
presynaptic inhibition of glutamate release
Topiramate
increases GABA transmission and inhibits glutamate (/AMPA which mimics glutamate).
Lacrosamide
binds to inactivated state of channels.
Benzodiazepines (GABAa Receptor)
Clonazepam:
sedation
Barbiturates (GABAa Receptor)
Phenobarbitone
Calcium Channels
Zonisamide:
blocks calcium channels
Ethosuximide: used in absence seizures
• Blocks T-type calcium channels.
Gabapentin (Pregabalin): blocks alpha2delta2 subunit of calcium channels.
• Pregabalin also increases GABA levels
Neurotransmitter Release
Levetiracetam:
bonds to synaptic protein SV2a
Neurotransmitter Uptake
Tiagabine:
Inhibits GAT-1 transporter for GABA
Neurotransmitter Synthesis
Vigabatrin:
inhibition of GABA transaminase, therefore protection of GABA
Neurotransmitter Receptors.
Perampanel:
selective non-competitive antagonist of AMPA receptors
Felbamata:
NDMA receptors.
