Neurodegenerative Disorders Flashcards
When neurons die can they be replaced?
No when neurons die they cannot be replaced
Name two neurodegenerative disease that causes death of neurons
-Alzheimer’s disease
-Parkinson’s disease
Which neurodegenerative diseases are responsible for protein folding
-Alzheimer’s disease
-Parkinson’s disease
Which protein is folded in Parkinson’s disease
a(Alpha )synuclein (mutations)
Which protein is misfolded in Alzheimer’s disease
-Beta-amyloid protiens(AB)
-Tau proteins
Describe mechanism of protein misfolding and how it causes pathology
-first genetic mutation leads to misfolding of proteins which can form and insoluble aggregate which gets deposited intracellular and extra cellular
-leading to neurotoxicity which is demonstrated by excitotoxicity ,oxidative stress and apoptosis and necrosis
What are the chief symptoms of Parkinson’s disease
-Bradykinesia
-muscle rigidity and when movement starts it cannot stop as well as initiate
-Tremor at rest
-cognitive impairment
What is the pathogenesis of Parkinson’s disease
Gradual loss of dopamine when the striatal dopamine content has fallen 20-40 % of normal
Parkinson’s disease is associated with what conditions
-dementia
-depression
-autonomic dysfunction
What are the mechanisms of action of Parkinson’s drug treatment
-you reduce the release of acetylcholine in striatum by increasing dopaminergic effects
-you block the NMDA receptors to inhibit release of acetylcholine
-Lastly you reduce acetylcholine by Muscarinic receptor antagonism
So in essence the drugs for Parkinson’s is classified into
*Dopaminomimetics
-NDMA receptor antagonist
-central Muscarinic cholinergic antagonists
List drugs for treatment of Parkinson’s disease
-levodopa with combination of carbidopa and as well as entacapone
Parkinson’s drugs mention 2 drugs that are dopamine agonists
-Bromocriptine
-Ropinirole
Pkd drugs- mention 2 Monamine oxidase B(MAO-B) inhibitors
-Selegiline
-resagiline
Cathechol-o-methyl transferase inhibitors
Entacapone
NMDA receptor blockers is ?
Amantadine
Muscarinic Acetylcholine receptor antagonists
Orphenadrine
Procyclidine
Pharmacokinetics of levodopa
*95% of levodopa is converted into dopamine in the intestine and can cause side effects only 5% gets into the brain
Side effects of levodopa
-Dyskinesia (involuntary movement)
-Hypotension
-schizophrenic like syndrome like hallucinations,night mares ,insomnia
-nausea and anorexia
Short notes on bromocriptide and why it was stopped
Bromocriptine, and cabergoline are dopamine agonists that are stopped due to side effects of fibrotic reactions in lungs , retroperitoneum and pericardium
Side effects of dopamine angonists ropinirole include
-over eating
-gambling and excessive sexual behavior
-hallucinations and somnolence
Good sides of dopamine agonists
-can improve mood
-have neurological protective activity
-D2/3 selective and better tolerated and do not show the fluctuations in efficacy
Unwanted side effects of muscarinic antagonists
-dry mouth
-constipation
-urinary retention
-Mydiarisis
-Tachycardia
Treatment of Parkinson’s disease and management which drug is contraindicated and what age?
-Patients age 65 we should not give muscarinic antagonist
Patient with age 50-70 with moderate motor disorders which drugs can we start with
Agonist of dopamine plus inhibitor of MOA)B amantadine, or muscarinic antagonists for patients less than 65
Age of patient 50-70 years with expressed motor and Cognitive Impairment which drugs should we administer
-start with levodopa
-if not improved add agonists of dopamine or inhibitor of MAO B or amantadine
Describe pathogenesis Alzheimer’s disease
Brain shrinkage and loss of focal cholinergic neurons in basal forebrain and hippocampus
Give 2 microscopic features of Alzheimer’s disease
-Amyloid plaques extra cellular deposits of Beta amyloid
-Intraneuronal neurofibrillary tangles (tau protein)
Give 3 drugs for treatment of Alzheimer’s disease
1-choline alfascerate(precursor of acetylcholine)400 mg
2-Cholinesterase inhibitors: Rivastigmine
Donepezil
Galantamine
3 antiexitotoxic agent: Memantine
