Applied Neuropharmacology Flashcards
Mesocortical pathway
cognition – deficient in schizophrenia causing negative effects
Mesolimbic pathway
reward pathways in the brain, area of addiction, upregulated in schizophrenia causing hallucination.
Nigrostriatal
involved in the voluntary control of movement – issue with Parkinson’s.
Tuberoinfundibular pathway
regulates the secretion of prolactin from the anterior pituitary gland. Some antipsychotic drugs block dopamine in the tuberoinfundibular pathway, which can cause an increase in blood prolactin levels (hyperprolactinemia). This can cause abnormal lactation (even in men), disruptions to the menstrual cycle in women, visual problems, headache and sexual dysfunction.
Dopaminergic drugs
DA precursor
-Levodopa
DA agonists
- Non-ergots
- ropinirole, pramipexole, rotigotine
Apomorphine - SC infusion
Enzyme inhibitors
Peripheral AAAD inhibitors eg carbidopa, benserazide
- MAOB inhibitors eg selegiline, rasagiline, safinamide
- COMT inhibitors eg entacapone, tolcapone
Results of dopaminergic drugs (ones that result in more dopamine)
Improve
Some motor features of Parkinson’s
e.g. limb rigidity & bradykinesia, tremor
Worsen or cause
- Nausea
- Vomiting
- Psychosis
- Impulsivity / abnormal behaviours
Fail to help
- “Midline” features
- eg dysathria, balance, cognition.
Dopamine antagonists results
Improve
- Nausea
- Vomiting
- Psychosis
Worsen or cause
-Parkinsonism
Vomiting and the BBB
DA antagonist antiemetics will worsen PD and generally should not be used in people with PD.
-Area postrema (vomiting centre) in the medulla is functionally OUTSIDE the BBB
Domperidone
DA antagonist
- Anti-emetic
- Does not cross the BBB
- No antipsychotic properties
- Relatively safe to use in PD
- Has permitted the therapeutic use of apomorphine (which is a powerful emetic).
Long term DA antagonist use
Antipsychotics / anti-dizziness
- Often cause parkinsonism
- e.g. receptor blockade in basal ganglia
-Sometimes cause dyskinesias
-Tardive dyskinesias (orofaciolingual)
Hard to explain: upregulation or increased sensitivity of certain DA receptors
