Applied neuro-pharmacology Flashcards
What is the limited range if neuro transmitters in the body
Acetylcholine
Monoamines
- Noradrenaline - Dopamine - Serotonin (5-HT)
Amino acids
- Glutamate - GABA - Glycine
Purines
- ATP - Adenosine
Neuropeptides
- Endorphins - CCK - Substance P
NO
How is Acetylcholine an exception of a neurotransmitter
Is inactivated by enzymatic breakdown in the synaptic cleft while most other transmitters are inactivated by high affinity uptake into neurones and glia
What three things does each neurotransmitter have
its own anatomical distribution
Its own range of receptors it acts on
Its own range of functions in different regions (some separated by the blood brain barrier)
What is the anatomical distribution of dopamine
Brain stem
Brain ganglia
Limbic system
Frontal cortex
What are the physical function affected by dopamine
Vomiting
Voluntary movements
Emotions/reward
What is the synthesis process of dopamine
Glycine –> alanine –> phenylalanine –> Tyrosine –> Levodopa–> Dopamine
What enzyme catalyses tyrosine to levodopa
tyrosine hydroxylase
What enzyme catalyses levodopa to dopamine
Aromatic aa decarboxylase
How in the periphery can dopamine production be stopped
Via pharmacologically
affecting the Aromatic aa decarboxylase enzyme
How in the brain can dopamine be stopped
Lost through degeneration affecting the tyrosine hydroxylase enzyme
What kind of receptors are dopamine receptors
Metabotropic (G protein coupled) receptors
What is the name of the the 5 subtype dopamine receptors
D1 - active adenylate cyclase
D2- inhibit adenylate cyclase
D3 - Inhibit adenylate cyclase
D4 - Inhibit adenylate cyclase
D5 - active adenylate cyclase
What are the key enzymes in dopamine metabolic breakdown
Monoamine oxidase B (MAO-B)
Catechol-O-methyltransferase (COMT)
What does dopamine metabolic breakdown to form
Homovanillic acid
What is the two cause of Parkinson’s
Degeneration of dopamine-secreting cells in substantia nigra
Dopamine secreting cell deficiency in basal ganglia
What is the presentation go Parkinson’s
Stiffness
Slow movements
Change in posture
Tremor
What are two categories of dopaminergic drugs
DA precursor
DA agonist
What is the DA precursor drug
Levodopa
What is different types of Dopamine agonists
Ergots:
- Bromocriptine
- Pergolide
- Cabergoline
Non-ergots
- Ropinirole
- Pramipexole
- Rotigotine
Apomorphine
What are enzyme inhibitor drugs used in the treatment of parkinson
Peripheral AAAD inhibitors
- Carbridopa
- Benserazide
COMT inhibitors
- Entacapone
- Tolocapone
MAO-B inhibitors
- Selegiline
- Rasagiline
- Safinamide
How does peripheral AAD inhibitors work in the treatment of parkinson
Decreases peripheral side effects of levodopa and allows greater proportion of the oral dose to reach the CNS
How does COMT and MAO-B inhibitors work in the treatment of Parkinsons
Decrease the metabolism of dopamine and so increase the effectiveness of levodopa
What features of Parkinson’s does dopaminergic drugs improve
Limb rigidity
Bradykinesia,
Tremor
What is the side effects of dopaminergic drugs (due to worsening or causing)
Nausea
Vomiting
Psychosis
Impulsivity / abnormal behaviours
Dyskinesias - abnormal involuntary movements (to much movement)
Dopaminergic drugs fail to help what features of Parkinson’s
Midline features:
Dysarthria
Balance
Cognition
What is the benefical affect of dopamine antagonist
Improve symptoms of nausea, vomiting, psychosis
Why cant most Dopamine antagonist be used as an antiemetics
As even though area postrema (vomiting centres) in the medulla is functionally outside the blood brain barrier, DA antagonist will still cross blood brain barrier and worsen or cause parkinsons disease
What dopamine antagonist doesn’t cross the blood brain barrier therefore can be used an an antiemetic
Domperidone
- relatively safe to use in parkinson
- no antipsychotic properties
What does domperidone permit therapeutic use of
Apomorphine
What is the affect of long term antagonist use
Antipsychotics / anti-dizziness
Often cause parkinsonism
Sometimes cause tardive dyskinesias (abnormal involuntary movements)
How does DA antagonist cause parkisonism
Receptor blockade in basal ganglia
Define tardive dyskinesias
A disorder that results in involuntary, repetitive body movements.
This may include grimacing, sticking out the tongue or smacking of the lips. Additionally there may be rapid jerking movements or slow writhing movements
How can long term DA antagonist sometimes cause dyskinesias
upregulation or increased sensitivity of certain DA receptor D2
How do tricyclic drugs and MAO inhibitors work as antidepressants.
By acting as a noradrenaline Reuptake inhibitors so noradrenaline remains longer in the system
What examples of drugs that affect serotonin 5-HT neurotransmitter
-Selective serotonin reuptake inhibitors (SSRIs) work as antidepressants.
Triptans selective 5HT agonists used for the treatment of migraine
What is the function of GABA neurotransmitters drugs
GABA agonists are anti-epilepsy drugs and they also have anti-anxiety properties.
