Applied neuropharmacology Flashcards
Describe synaptic transmission
- neurotransmitter usually packed into vesicles at the presynaptic terminal
- Sodium action potential reaches the termina
- voltage gated calcium channels open
- Triggers calcium dependant exocytosis of the packaged vesicles into the synaptic cleft
- The neurotransmitter diffuses across the cleft and binds to the receptors of the post-synaptic terminal to produce a response
- Presynaptic autoreceptors inhibit further release of neurotransmitter by binding to the calcium channels and blocking them
- The neurotransmitter is usually inactivated by being reuptaken into glia or neurons
What is an ionotropic receptor
Has an integral ion channel
What is a metabotropic receptor
Coupled to a G protein
How does a competitive antagonist work
It binds to the same receptor as the neurotransmitter - it has a high affinity for the receptor - but it has a low efficacy and doesn’t produce an effect but just acts as a blocker
How does a non-competitive antagonist work
Binds to another site so has low affinity and efficacy - but it changes the shape of the receptor site for the neurotransmitter so reduces binding
What drug can block the reuptake of a transmitter
SSRI
Why is nitrous oxide an unorthodox neurotransmitter
It is not packaged into vesicles but instead, freely diffuses out of cells
What happens in Parkinsons disease
Degeneration of dopaminergenic cells in the substantia nigra
How does low dopamine occur in the brain
- Tyrosine converts into DOPA which gets converted into dopamine
- Tyrosine cannot cross the blood brain barrier but DOPA can
- When the enzyme which causes Tyrosine to DOPA degenerates, dopamine cannot be produced in the brain
What are the key enzymes in the breakdown of dopamine
MAO-B and COMT
What are the classical signs seen in parkinsons disease
- Stiffness
- Slow movements
- Change in posture
- Tremor
What are examples of Dopamine agonists
Ergots - bromocrriptine, pergolide and cabergoline
Non-ergots = ropinirole, pramipexole and rotigotine
Apomorphine
What is an example of a dopamine precursor
Levodopa
What drugs improve symptoms in Parkinsons disease
DA precursor
Levodopa
DA agonists
Ergots:
Bromocriptine, pergolide, cabergoline
Non-ergots
ropinirole, pramipexole, rotigotine
Apomorphine
What drugs increase effect of levodpa and increase dopamine
MAOB inhibitors: selegiline and rasagiline
COMT inhibitors - entacapone and opicapone
What are the side effects of dopaminergic drugs
- Nausea
- vomiting
- psychosis
- impulsivity and abnormal behaviours
What type of antiemetics should be avoided in patients with parkinsons disease
Dopamine antagonist antiemetics that can cross the blood brain barrier
What is an example of a dopamine antagonist that doesnt cross the blood brain barrier and is therefore fine to be used as an antiemetic in parkinsons patients
Domperiodne
