Applied Neuro-Pharmacology Flashcards
Sequence of events in synaptic transmission?
- Packaging of neurotransmitter in presynaptic terminals
- Na AP in presynaptic terminal
- AP opens Ca gated channels
- Ca triggers package of neurotransmitter exocytosis
- Transmitter diffuses across cleft, binds receptors
- Transmitter inactivated by uptake or by extracellular breakdown
- Transmitter metabolized
What sort of manipulations to synaptic transmission could reduce synaptic transmission?
- Block AP (local anaesthetics)
- Block Ca channels
- Block transmitter release
- Block postsynaptic receptors (allows for selectivity)
- Increase transmitter breakdown / uptake
- Inhibit transmitter synthesis
What sort of manipulations to synaptic transmission could increase synaptic transmission?
- Use a transmitter agonist
2. Block transmitter break down / uptake
What class of transmitter is dopamine?
Monoamine
- along with noradrenaline & serotonin
What can help separate transmitters in the brain from having adverse actions elsewhere in the body (eg. in the PNS)?
The blood brain barrier
Where is dopamine anatomically distributed in the brain?
- Brain stem
- Basal Ganglia
- Limbic system and Frontal cortex
Which physiological functions are affected by dopamine?
- Voluntary movement
- Emotions / reward
- vomiting
Where does the mesolimbic pathway run between? What brain functions is it involved in?
Consequences of overactivity?
- Ventral Tegmental Area (VTA) of midbrain to Ventral Striatum of the basal ganglia
- Involved in motivation and reward
- Overactivity leads to positive schizophrenia sx and hallucinations in PD
Where does the mesocortical pathway run between? What brain functions is it involved in?
Consequences of impairment?
- Connects VTA of midbrain to prefrontal cortex
- Involved in executive function and cognition
- Impairment causes reduced cognition in PD and effects in schizophrenia
What are the four main dopaminergic pathways of the brain?
- Mesocortical
- Mesolimbic
- Nigrostriatal
- Tubero-infundibular
What is the Tubero-infundibular pathway involved in?
- Inhibition of prolactin
hormone for producing breastmilk
Where does the nigrostriatal pathway extend from?
What is its main function?
- Connects the substantia nigra with the basal ganglia
- Critical in the production of movement as part of the basal ganglia motor loop
What causes the effects of Parkinson’s Disease (PD)?
Degeneration of dopaminergic cells in the substantia nigra (SN)
- Therefore dopamine deficiency in basal ganglia
Precursors during dopamine synthesis?
- Glycine
- Alanine
- Phenylalanine
- Tyrosine
- DOPA (dihydroxyphenylalanine)
- Dopamine
What type of receptor does dopamine act on? How many subtypes of receptor are there for dopamine?
- Metabotropic (G-protein coupled)
- 5 different subtypes of receptor (all either activate or inhibit adenylate cyclase)
What is the consequence of dopamine having multiple different receptors?
- Dopamine can have many effects, and produce different effects in different brain regions depending on which receptors are expressed
What are the key enzymes in dopamine breakdown?
- Monoamine oxidase B (MAO-B)
- Catechol-O-methyltransferase (COMT)
What effects does the loss of dopamine cause in PD?
- Stiffness
- Slow movements
- Change in posture
- Tremor
What are some dopaminergic drugs?
Dopamine Precursor:
- Levodopa
Dopamine Agonists:
- Ergots (bromocriptine, pergolide)
- Non-Ergots (ropinirole, pramipexole)
- Apomorphine
(improve some symptoms of PD)
What enzyme converts DOPA to Dopamine? Where can it be blocked? Effects of blockage?
- AAAD
- Can be blocked in the PNS (carbidopa),
- reduces peripheral side effects of PD and allows more DOPA to reach CNS
What is the effect of MAOB and COMT inhibitors?
Reduce the metabolism of dopamine
- Therefore increase effectiveness of levodopa
What are the positive effects of dopaminergic drugs?
Improve:
- Some motor features of PD, eg: limb rigidity, bradykinesia and tremor
What are the negative effects of dopaminergic drugs?
- Nausea
- Vomiting
- Psychosis
- Impulsivity / abnormal behaviours
What symptoms of Parkinson’s are not helped by dopaminergic drugs?
Midline Features, eg:
- Dysarthria (unclear speech)
- Balance
- Cognition
