Applied Neuro-Pharmacology Flashcards
What approaches ca be used to reduce synaptic transmission?
Blocking the voltage gated sodium channels
Blocking the voltage gated calcium channels
Inhibiting the packagaing mechanism
Blocking the release machinery
Blocking the postsynaptic receptors
Activating presynaptic inhibitory receptors
How do local anaesthetics manipulate synaptic transmission
Reduce transmission by blocking the voltage gated sodium channels and thereby blocking any sodium from entering the neuron post AP, therefore blocking all release
How do substances such as spider toxins manipulate synaptic transmission?
Reduce it by blocking voltage gated calcium channels, thereby blocking all transmitter release
How does Botox manipulate synaptic transmission?
Reducing it by blocking the presynaptic release machinery
How do receptor antagonists manipulate synaptic transmission?
They reduce it by blocking the postsynaptic receptors
What approaches can be used to increase synaptic transmission?
Increasing synthesis by flooding the cells with appropriate precursor
Blocking breakdown of the transmitter
Blocking uptake of the transmitter
Activating the postsynaptic receptors
How do benzodiazepines and barbituates acting on GABA receptors manipulate synaptic transmission?
THey increase it by activating the postsynaptic receptor whilst potentiating the effects of the endogenous transmitter
How do anticholinesterases acting on ACh manipulate synaptic transmission?
Increase it by blocking breakdown of the transmitter
Name the monoamine class of neurotransmitter
Noradrenaline
Dopamine
Serotonin (5-HT)
Name the amino acid class of neurotransmitter
Glutamate
GABA
Glycine
Name the purine class of neurotransmitter
ATP
Adenosine
Name the neuropeptide class of neurotransmitter
Endorphins
CCK
Substance P
Name the two neurotransmitter which do not belong to a class or group
Acetylcholine
NO
Does each neurotransmitter have only one specific function?
No, each have multiple different functions in different areas
What separates the brain from the peripheral nervous system?
BBB
Where is dopamine distributed in the brain?
Brain stem
Basal ganglia
Limbic system/frontal cortex
What physiological functions are affected by dopamine?
Vomiting
Voluntary movements
Emotions
What happens to DA in Parkinson’s disease?
Degeneration of DA cells in the SN (nigrostriatal pathway)
Leads to DA deficiency in the basal ganglia. Leads to stiffness, slow movements, change in posture, tremor
Can in theory both selective agonists and selective antagonists produce a beneficial effect with respect to dopamine?
Yes in theory either could
What are the key enzymes in dopamine breakdown?
MAO-B
COMT
Give a dopaminergic DA precursor drug
Levodopa
Give some dopaminergic DA agonist drugs
Bromocriptine, pergolide
Ropinirole
Pramipexole
Apomorphine
What are some enzyme inhibitors used in the treatment of Parkinson’s?
Peripheral AAAD inhibitors - carbidopa, benserazide. Reduce peripheral side-effects of levodopa to allow a greater proportion of the dose to reach the CNS
MAOB inhibitors - selegiline. Reduce the metabolism of dopamine so increase the effectiveness of levodopa.
COMT inhibitors - entacapone. Same effect as MAOB inhibitors
What are the pros and cons of dopaminergic drugs?
Pros - Parkinson’s e.g. rigidity and bradykinesia in the limbs
Cons - nausea, vomiting, psychosis
Cannot help - ‘midline’ features such as dysathria, balance, cognition
Describe the relationship between the BBB and vomiting
DA antagonist aniemetics will generally worsen PD and should therefore be avoided in patients with PD. This only applies because the antiemtic will cross the BBB. This is not necessary in theory, however, as the area postrema/vomiting centre us functionally outside the BBB in the medulla. For this reason domperidone is used, - a DA antagonist antiemtic which does not cross the BBB
What are the features of domperidone?
DA antagonist Anti-emtic Does not cross BBB No antipsychotic properties Relatively safe for use in PD Has permitted the therapeutic use of apomorphine (powerful antiemetic)
What are dyskinesias?
Abnormal involuntary movements
Should anti-emetic DA antagonists be used long term?
No, long term vomiting doesn’t happen
Should anytipsychotic DA antagonists be used long term?
Yes, there is often no alternative
What is the major side effect of long term DA use?
Often cause parkinsonism
