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Flashcards in Neurodegenerative disease therapies Deck (20)
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1
Q

What are the goals of therapy for parkinsons?

A
  • 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
2
Q

How does Levodopa?

A
  • precursor to DA but it crosses the BBB (DA does not)
    • converted to DA once it crosses
  • administered with peripheral decarboxylase inhibitor
3
Q

Levodopa side effects

A
  • 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
4
Q

What is levodopa dosed with and why?

A
  • 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
5
Q

what lab measurements would might you expect for a pt on levodopa?

A
  • urinary metabolites can cause false positive tests for ketoacidosis
  • transient increase in BUN
  • increase in liver enzymes
6
Q

What drugs interact with Levodopa?

A
  • 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
7
Q

How do the decarboxylase inhibitors decrease the incidence of N/V and cardic dysrhythmias?

What are two of these drugs?

A
  • 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
8
Q

How do COMT inhibitors affect levodopa?

What are two of these drugs?

A
  • COMT is responsible for peripheral breakdown of levodopa
  • by blocking it, the elimination of levodopa is slowed
  • Tolcapone (tasmar)
  • Entacapone (comtan)
9
Q

How do synthetic dopamine agonists work?

What are three of these drugs?

A
  • 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
        *
10
Q

What are the side effects of the synthetic dopamine agonists?

Which are more preferred?

Why?

A
  • Side effects:
    • sedation, vivid dreams, hallucinations
  • non ergots preferred
    • less nausea and orthostatic hypotension
11
Q

What are the anticholinergics that are used to treat Parkinsons?

What do they do?

side effects?

A
  • 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
12
Q

What is Amantadine? How does it work?

A
  • Enhances DA release into the synapse and delays reuptake
  • improves parkinsons symptoms
13
Q

What is Selegiline?

A
  • highly selective irreversible inhibitor of MAO B
  • used as an adjunct to carbidopa-levodopa
  • increases the intrasynaptic half time of DA
14
Q

What are the symptoms of Alzheimers?

problems with…

A
  • memory
  • language
  • judgment and thinking
  • personality
  • perception
15
Q

Who gets alzheimer’s disease?

A
  • 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
16
Q

What is the pathology of alzheimers?

A
  • Deficits in cholinergic signaling
  • neuron loss in hippocampus (memory and learning) and frontal cortex (executive function)
  • Causes decreases in:
    • choline acetyltransferase activity
    • acetylcholine amount
    • acetylcholinesterases
    • choline transport
    • nicotinic acetylcholine receptor expression
  • also have Anymoid placques and neurofibrillary tangles on the neurons
    • interferes with message transmission and cell death
17
Q

What are the two major treatments of alzheimers?

A

Cholinesterase inhibitors

NMDA receptor antagonist

18
Q

What are the three cholinesterase inhibitors?

MOA?

A
  • Donepezil (Aricept)
  • Rivastigmine (exelon)
  • Galantamine (Razadyne)
  • MOA
    • prevents action of acetylcholinesterase, thereby increasing concentration of ACh
19
Q

What is the NMDA receptor antagonist?

what is it indicated for?

A
  • Memantine (namenda)
  • indicated for moderate to severe AD
  • very modest benefits
20
Q

How does Memantine work?

A
  • Blocking “leaky channels to reduce calcium induced excitotoxicity
    • helps reduce the background noise, making the signals relatively stronger