Neurodegenerative disease therapies Flashcards
What are the goals of therapy for parkinsons?
- enhance inhibitory effect of dopamine
- increase amt of DA
- drug therapy that mimics DA
- decrease excitatory effect of acetylcholine
- treatment is palliative- does not stop progression of disease
How does Levodopa?
- precursor to DA but it crosses the BBB (DA does not)
- converted to DA once it crosses
- administered with peripheral decarboxylase inhibitor
Levodopa side effects
- N/V
- CV
- stimulation of a & b
- Increased BP, tachycardia
- orthostatic hypotension
- PAC’s, PVC’s
- abnormal involuntary movements- tics, grimacing
- develops after 1-4 months of therapy in 50% of patients
- psychiatric disturbances
What is levodopa dosed with and why?
- Carbidopa (decarboxylase inhibitor)
- entacapone (COMT inhibitor)
- added when the effectiveness of Levo/carbidopa wanes
- so that the same amount of levodopa that is administered makes it to the brain, otherwise a large dose would have to be administered just for a little bit to make it
- If levodopa is given by itself, only 5% makes it to the brain
what lab measurements would might you expect for a pt on levodopa?
- urinary metabolites can cause false positive tests for ketoacidosis
- transient increase in BUN
- increase in liver enzymes
What drugs interact with Levodopa?
- Butyrophenones and phenothiazines
- antagonize the effect of DA
- metaclopramide- worsense effects of disease
- Droperidol- skeletal muscle rigidity and pulmonary edema from sudden antagonism of DA
- MAOIs- interfere with inactivation of catecholes including DA
- anticholinergics- act synergistically with levodopa to improve tremor
How do the decarboxylase inhibitors decrease the incidence of N/V and cardic dysrhythmias?
What are two of these drugs?
- they prevent the dopamine from having a systemic effect.
- DA in the periphery can cause N/V and affect cardiac function?
- Carbidopa (Sinemet)- levodopa and carbidopa
- Benserazide (Madopar)- Levodopa and benserazide
How do COMT inhibitors affect levodopa?
What are two of these drugs?
- COMT is responsible for peripheral breakdown of levodopa
- by blocking it, the elimination of levodopa is slowed
- Tolcapone (tasmar)
- Entacapone (comtan)
How do synthetic dopamine agonists work?
What are three of these drugs?
- Act directly on post synaptic dopamine receptors
- no enzyme reaction required
- longer 1/2 life than levodopa
- drugs:
- Bromocriptine (parlodel)
- ergot derivative
- Pramipexole (mirapex)
- non ergot
- Ropinirole (requip)
- non ergot
*
- non ergot
- Bromocriptine (parlodel)
What are the side effects of the synthetic dopamine agonists?
Which are more preferred?
Why?
- Side effects:
- sedation, vivid dreams, hallucinations
- non ergots preferred
- less nausea and orthostatic hypotension
What are the anticholinergics that are used to treat Parkinsons?
What do they do?
side effects?
- Trihexyphenidyl (artane) and Benztropine (cognetin)
- Blunt effects of excitatory neurotransmitter ACh, correcting the balance between DA and ACh
- side effects:
- confusion, hallucination, confusion
- urinary retention
What is Amantadine? How does it work?
- Enhances DA release into the synapse and delays reuptake
- improves parkinsons symptoms
What is Selegiline?
- highly selective irreversible inhibitor of MAO B
- used as an adjunct to carbidopa-levodopa
- increases the intrasynaptic half time of DA
What are the symptoms of Alzheimers?
problems with…
- memory
- language
- judgment and thinking
- personality
- perception
Who gets alzheimer’s disease?
- 5% at 65 years old
- >90% at 95 years old
- Early onset: when symptoms appear before age 60
- genetic factors
- late onset: symptoms after 60 years
