CNS 2: neurodegeneration Flashcards
Parkinson’s disease major symtopms
Resting tremor Bradykinesia, akinesia Muscular rigidity postural instability Dementia TRAP- Tremor, Rigidity, Akinesia, Postural
Structures in the brain responsible for parkinsons
neostriatum and Extrapyramidal motor system (EPS)
Damage depresses:
1. the ability to initiate movement
2. causes involuntary movements
COMT in Dopamine degradation
Degrades LDOPA Dopamine DOPAC Post synaptic neuronal and interneuronal membranes
MAO-B
Degrades DDompamine into DOPAC in the brain
Aromatic AA Decarboxylase (AAD)
Converts LDOPA to Dopamine
Tyrosine Hydroxylase
Converts Tyrosine to LDOPA
Dopamine beta Hydroxylase
Converts dopamine to norepinephrine
D1 receptors
increase inhibitory output from the neostriatum to the basal ganglia which allows excitatory inputs into the neocortex
D2 receptors
an indirect pathway that ultimately leads to the excitation of the motor cortex
Dopamine precursor therapy
Levo DOPA- Dompamine precursor
Carbidopa- inhibits peripheral AAD so L-DOPA can get into the brain
limitations of treatment
1. wears off after 2-5 years
2. Dyskinesias develop after 5-8 years
3. On-Off phenomenon- dyskinesias one day then off (no relief of symptoms)
Dopamine receptor agonists- Ergots
bromocryptine
pergolide
Side effects:
Compulsive behavioe- sex,alcoholism, eating, porn
Dopamine Receptor agonists- non ergots
Pramipexole Ropinorole Rotigotine Apomorphine Side effects: Compulsive behavioe- sex,alcoholism, eating, porn
Bromocryptine
D2 agonist, D1 antagonist Treats: hyperProlactinemia Side effects: must be titrated slowly due to acute hypotension pleural effusion, cough, shortness of breathe, pulmonary fibrosis not as effective against motor symptoms nausea fatigue hallucinations gi disturbances
Apomorphine
non ergot DAR agonist
therapy for sudden off phase
can cause psychosis drowsiness and hypersexuality
emesis , hypotension
COMT Inhibition
Entacapone
Talcapone- alot of diarrrhea (more than usual)
both cause urine discoloration
