Applied neuropharmacology Flashcards
Which neurotransmitter is unusually inactivated by extracellular breakdown? What is the other usual method to inactivate neurotransmitters?
acetylcholine
inactivated by uptake into glial neurons
3 places of anatomical distribution of dopamine in the brain
brainstem
basal ganglia
limbic system and frontal cortex
3 physiological functions affected by dopamine
reward system
vomiting
voluntary movements
What causes Parkinson’s?
degeneration of DA cells in substantia nigra and DA deficiency in basal ganglia
symptoms of parkinson’s
stiffness, slow, movements, tremor, change in posture
Precursor of dopamine
L-Dopa, tyrosine
Can dopamine cross the blood brain barrier?
No
What type of receptors are dopaminergic and how many are there?
metabotropic
D1-5
Consequence of no ionotropic dopamine receptors
cannot evoke fast IPSP/EPSP
2 key enzymes in dopamine breakdown
MOA-B
COMT
Examples of dopaminergic drugs
precursor eg levodopa
DA agonist eg ergots, non-ergots, apomorphine
What do dopaminergic drugs do to PD symptoms?
improve them
3 types of enzyme inhibitors used in PD
peripheral AAD inhibitor
COMT inhibitor
MOA-B inhibitor
Peripheral AAD inhibitors effect on levodopa
reduce peripheral side effects
increase oral does reaching CNS
COMT inhibitors effect on levodopa
decrease DA metabolism and so increase levodopa effectiveness
Do enzyme inhibitors have an effect on synthetic dopaminergic agonists?
no
3 motor features of PD dopaminergic drugs improve
tremor
limb rigidity
bradykinesia
What can dopaminergic drugs worsen or cause?
nausea, vomiting, psychosis, impulsiveness
What do dopaminergic drugs fail to help?
midline features eg balance, cognition, dysarthria
What do dopamine antagonists improve and worsen?
improve - vomiting, nausea, psychosis
cause - PD
What anti-emetics should not be used in people with PD?
DA antagonist
Is the vomiting centre in medulla functionally inside or outside the blood brain barrier?
outside
What DA antagonist does not cross blood brain barrier?
Domperidone
What Is domperidone?
DA antagonist, does not cross BBB, anti-emetic, safe in PD, no antipsychotic properties, has permitted therapeutic use of apomorphine
What drug has domperidone allowed use of? what class of drug is this?
apomorphine
dopaminergic agonist - strong emetic
What may dopaminergic drugs cause? dyskinesia or parkinsonism?
dyskinesia
What may DA antagonist cause? parkinsonism or dyskinesia?
Parkinsonism
Long term DA antagonists used for? what do they cause and why?
anti-psychotics, anti dizziness
Parkinsonism - block receptor in basal ganglia
