Parkinson's Disease
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what is Parkinson's disease characterised by?
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what is Parkinson's disease caused by?
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what does pharmacological treatment aim to do for Parkinson's?
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insidious onset, with slowing of voluntary movement, muscular rigidity, postural abnormality & tremors
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the striatal deficiency of dopamine following neuronal degeneration within the substantia nigra
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restore dopamine levels in basal ganglia
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reduce the excitatory effect of acetylcholine
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what drugs do we use to treat Parkinson's?
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what are examples of each?
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what is the mechanism of action of each?
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dopamine precursors
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levodopa
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metabolic precursor of dopamine, that is converted to dopamine by aromatic L-amino acid decarboxylase (AADC)
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inhibitors of dopamine metabolism
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carbidopa
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inhibits AADC in peripheral tissues to increase availability of levodopa in the CNS by allowing more to cross the BBB before being converted to dopamine
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dopamine receptor agonists
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bromocriptine, pramipexole, etc
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agonists at dopamine D2 receptors, working to restore dopamine signalling in the striatum
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antimuscarinic drugs
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benzatropine
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selectively blocks activity at the M1 muscarinic acetylcholine receptor, reducing cholinergic activity in the basal ganglia and restoring the ‘balance’ of acetylcholine and dopamine
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amantadine
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-
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unknown, but thought to weakly inhibit the NMDA and nicotine receptors, as well as activate dopamine receptors
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Alzheimer's Disease
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what are the 3 distinguishing features of Alzheimer's disease?
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accumulation of senile plaques (b-amyloid accumulations)
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formation of numerous neurofibrillary tangles
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loss of cortical neurons (especially cholinergic neurons)
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what are the drugs used to treat Alzheimer's disease?
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what is an example of each?
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what is the mechanism of action of each?
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acetylcholinesterase inhibitors
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donepezil, rivastigmine, etc
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preferentially inhibits acetylcholinesterase (AchE) in the CNS over peripheral enzymes
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NMDA receptor antagonists
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memantine
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uncompetitive antagonists at glutamatergic NMDA receptors
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Motor Neuron Disease
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what is motor neuron disease?
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a group of related neurodegenerative diseases that affect motor neurons and therefore voluntary muscle control
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what is an example of a motor neuron disease?
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amyotrophic lateral sclerosis (ALS) etc
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what are the physical effects of motor neuron disease?
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loss of motor neurons and muscle control until the patient can no longer eat, speak, move or breathe, with respiratory failure being the usual cause of death
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what are the drugs indicated specifically for motor neuron disease?
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riluzole, baclofen, edaravone, tizanidine
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what are the mechanisms of action of the first drug thought to be?
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binding to glutamate receptors to reduce the release of glutamate
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preferentially blocking TTX-sensitive sodium channels, which are linked to neuronal damage
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allosterically binding to GABAA receptors on post- synaptic neurons
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