Neurodegenerative disorders 2 Flashcards
(38 cards)
what neurotransmitters are affected in HD?
decrease in GABA and GAD
decrease in ACh and acetyltransferase
dopamine remains unchanged or slightly increases
what are the general facts about huntingtons disease ?
gradual onset
progressive development
main symptoms= chorea and dementia
selective cell loss in cerebral cortex, corpus straitum
it is a mirror image of parkinsons disease but it does have some similarities
what pathways are lost in HD?
loss of GABAergic pathways
- pathway from globus pallidus & substantia nigra pars reticulata to the thalamus
- pathway from globus pallidus external segment to the subthalamic nucleus
what is the treatment for HD ?
no cure- death is inevitable
no symptomatic relief - drugs to increase GABA and ACh you would expect to work but it doesnt because GABA is the ubiquitous inhibitory neurotransmitter so increasing it would cause worse effects
what can be used to control the movement disorders in HD?
dopamine-2 antagonists such as haloperidol and chlorpromazine- important to get dose right to prevent PD symptoms occurring
dopamine depletion such as reserpine and tetrabenzine
what are the adverse effects of dopamine antagonists and dopamine depletion ?
dopamine 2 antagonists- parkinsonism and restlessness
da depletion- hypotension, depression, sedation and GI disturbances
what are some general characteristics of progressive supranuclear palsy ?
idiopathic
affects subcortical grey matter
progressive dementia
motor symptoms= opthalmoplegia (inhibits eye movements, first vertically then horizontally), balance/posture impaired, pseudobulbar palsy, exaggerated, bradykinesia/rigidity
what neurotransmitters are affected in progressive supranuclear palsy ?
decrease in dopamine in the caudate nucleus and cerebellum
what are the treatments for PSP?
dopaminergic preps for rigidity/bradykinesia e,g,L-DOPA
anticholinergics for gait, speech, pathologic laughing/crying- help to treat inappropriate emotional responses
methysergide for dysphagia
dementia is untreatable
ONLY TREATMENT FOR SYMPTOMATIC RELIEF - treatment depends on what patients respond to
what are the general facts about CBGD?
rare bradykinesia/rigidity like in PD apraxia and clumsiness postural instability myoclonus - chronic contraction of skeletal muscle atrophy of frontal and parietal cortex
what are the treatments for CBGD?
NO TREATMENT
PD treatments are ineffective - no symptomatic treatments
what are the general facts about amyotrophic lateral sclerosis?
starts at about 30-60 years
degeneration of the anterior horn cells
muscle denervation- loss of lower motor neurons
90-95% is sporadic and 5-10% is due to familial mutations in SOD
what could the sporadic form of ALS be due to ?
glutamate excitotoxicity - too much activity at NMDA and AMPA and kainate receptors
- causes too much calcium in cells and this can lead to apoptosis and necrosis when the concentrations are too high
what are the treatments for motor neurones disease ?
anticholinergics - atropine and aytriptyline- for drooling because it decreases salivary secretions
RILUZOLE
- inhibits glutamate release
- increases glutamate uptake into glial cells and neurons
- prolongs survival by about 3 months
- may slow progression- prolong time before patient has to have mechanical ventilation which makes you completely house bound
- no attenuation of motor effects - still have muscle paralysis
what are the adverse effects of treatment for motor neurons disease ?
fatigue dizziness GI disorders reduced pulmonary function increases liver enzymes- need to be careful if patient is taking other drugs
what are the general facts about picks disease ?
frontotemporal dementia
2-3% of all dementia
20-25% of all frontotemporal dementias
no known genetic factor but 45% of patients have a first degree relative with frontotemporal dementia
- personality changes, emotional changes, speech - it is typified by the personality changes
what neurotransmitters change in picks disease ?
decreases in serotonin receptors and serotonin levels
ChAT is unchanged
CSF and brain dopamine is unchanged
CSF and brain somatostatin decreased
what are the treatments for Picks disease ?
NONE
acetylcholineesterase inhibitorss are largely ineffective
what are the general facts about Alzheimer’s disease ?
most common causes of dementia
senile dementia (>65yrs) and presenile dementia (60 years
death is normally within 5-10 years
what are generally the causes of death from AD?
infection
inanition- inability to eat
stroke- amyloid beta protein has adverse effects on cerebrovasculature leading to haemorrhagic stroke
what is the seriously worrying fact about AD?
the number of sufferers will double in the next 20 years
- this is a serious problem with our ageing population
what is the link between nictonic receptors and AD?
there is an age related decrease in nicotinic receptors however this reduction is much larger in AD patients
- younger AD patients have much less nicotinic receptors, it is even less than the age related decrease
what is the most common treatment in AD ?
AChE inhibitors
- tacrine and donepezil
- inhibit AChE reversibly
- increases acetylcholine levels
- may slow progression but only by about 6 months
- may improve cognition in some individuals
DONT WORK IN EVERYONE
when was tacrine first used ?
used in america in 1996 but it was hepatotoxic
