Parkinson's Treatment Flashcards
Understand the pathophysiology of Parkinson's disease and how to treat the disease. The drugs MOA, clinical uses, and toxicities.
How do typical antipsychoitics work?
Typical antipsychoitics work by inhibiting 70-80% of D2 receptors (mesolimbic/mesocortical. Atypicals are used mainly to treat positive symptoms such as dellusions, hallucinations, etc. They also can inhbit the Dopaminergic neurons of the basal ganglion causing motor side effects like Parkinson’s DIsease.
haloperidol
butyrophenones: high potency, high incidence of motor effects. Little anticholinergic, antiadrenergic effects.
l-Dopa (MOA and Use)
l-dopa crosses the BBB and in the brain is converted into Dopamine. This is used to treat PArkinson symptoms, but des not slow down the disease process (still nigrostriatal Dopaminergic degradation).
What is the disease pathophysioloy of Parkinson’s disease?
In Parkinson’s disease, the Dopaminergic neurons of the substantia nigra are lost. This causes the intrastriatal ACh neurons to fire uncontrollably (lost inhbition).
What histology is seen in Parkinson’s disease?
Lewy body aggragation (alpha-synuclein).
l-dopa Toxicities
Dopamine concentration increases peripherally leading to orthostatic hypertension and cardiac arrhythmias. Vomiting is stimulated by DA hitting the area postrema in the medulla. Dry mouth, abdominal pain, burning tongue. Phyciotic side effects (dellusions, confusion, from DA activation of meso cortical/meso-limbic tract.
What drug is always given with l-dopa and how effective is l-dopa treatment (long-term)?
Always give carbidopa with l-dopa because l-dopa is broken down peripherally (AAAD and COMT). It has a short half life, so give extended release. Also, it is not a very effective long term treatment. There is a toerance/weaning off seen ater 5-6 years (time and dose dependent). Start with low doses and then build.
Carbidopa
INhibits AAAD in periphery; dose not cross BBB. AAAD usualy converts l-dopa into DA. Carbidopa does not cross BBB, so wont affect l-dopa degradation centrally.
Entacapone
Inhibits COMT (degrades l-dopa into 3-methyldopa) in the periphery. Give with l-dopa especially when there is wearing off an on-off effect.
Selegiline
At therapeutic dose Inhibit MAO-B (usually degrades DA into DOPAC at the nerve synapse. - therefore DA concentation levels rise centrally. At high doses, it inhibits MAO-A (NE and 5-HT).
When would you use selegiline? And what toxicities dose this drug have? What two syndromes are associated with selegilines use?
When l-dope is insufficient or intolerable. Vomiting (area postrema), orthostatic hypotension (DA in periphery), tyramine reaction (tyramine causes DA to be released from nerve terminals results in hypertensive crisis). Also serotonin syndrome may result if given with fluoxetine or meperidine (SSRIs).
What are the 4 drugs that act as DA receptor agonists?
Ergot derivative: 1) bromocriptine and 2)apomorphine, and the non-ergot dervatives: 3) ropinirole and 4) pramipexole
Apomorphine
injection for immobility (D2 and D3 agonists)
Roprinirole, MOA and Toxicities
D2 and D3 agonists (non-ergot derivative DA agonist). Can precipitate psychoitic behavior and HYPOPROLACTEMIA. Used early in disease with l-dopa, but at low doses. Last stage effort when l-dopa fails.
How is roprinirole metabolized?
CYP1A2 system. Do not give with ciprofloxacin or fluoxamine.
