CNS II- Neurodegenerative Disorders/ Parkinson's Disease Flashcards Preview

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Flashcards in CNS II- Neurodegenerative Disorders/ Parkinson's Disease Deck (35)
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1
Q

What is neurodegeneration?

A

Progressive loss of neuronal function, typified by neuronal cell death (apoptosis or necrosis) and protein aggregates (inclusion bodies)

2
Q

What are the 4 main neurodegenerative disorders to know?

A
  1. Alzheimer’s (most common)
  2. Parkinson’s
  3. Huntington’s
  4. Amyotrophic Lateral Sclerosis (ALS)
3
Q

What kind of inclusion bodies are associated with Parkinson’s disease?

A

Lewy bodies

4
Q

What are the major symptoms of Parkinson’s disease?

A

Major Symptoms of Parkinson’s disease:

  • Resting tremor (abates during voluntary movement)
  • Bradykinesia, akinesia (slowness, lack of movement)
  • Muscular rigidity
  • Postural instability (disturbances of gait, falling {PD+})
  • Dementia

“TRAP”–> tremor, rigidity, akinesia, postural

5
Q

Which neurons are destroyed in Parkison’s disease?

A

The dopaminergic neurons that project to the neostriatum from the substantia nigra pars compacta are selectively and progressively destroyed.

6
Q

What forms the extrapyramidal motor system (EPS)?

A

The neostriatum (basal ganglia)

7
Q

What happens when the EPS is damaged?

A
  • Depression in the ability to initiate voluntary movements

- Causes involuntary movements (ie/ resting tremor, huntington’s)

8
Q

What are the risk factors for developing Parkinson’s?

A
  • Genetic (10-15% familial)
  • Age
    - illness (CNS infection, perhaps viral)
  • Environment toxins (herbicides, rotenone, MPTP)
  • Oxidative stress
    - mitochondrial dysfunction
    - nitric oxide production
    - loss of reduced glutathione
  • Glutamate excitotoxicity
  • Protein misfolding and impaired degradation
    - Mutations, e.g. Parkin, polygenetic origins
9
Q

What is the net result of the direct DA pathway?

A

Produces excitatory input to the motor cortex

10
Q

What is the net result of the indirect DA pathway?

A

Produces inhibitory input to the motor cortex. HOWEVER–> D2 inhibits the indirect pathway, which ultimately produces excitatory input to motor cortex

11
Q

What is the major goal of pharmacological treatment in PD?

A

Major goal of pharmacological treatment of PD is to improve DA neurotransmission from the SNpc to the neostriatum.

This is accomplished by attempting to elevate DA levels in the SNpc

12
Q

Why don’t we use dopamine to treat PD?

A

Because it does not cross the BBB

13
Q

What are the dopamine precursors?

A

Levodopa
Carbidopa- inhibits peripheral conversion of L-DOPA to dopamine (inhibits AAD)
Levodopa/Carbidopa (#1 initial therapy for PD)

14
Q

What are the dopamine receptor agonists?

A
Pergolide (PERMAX) (taken off the market--> side effect of cardiac valve regurgitation)	 
Bromocriptine (PARLODEL) 
Ropinirole (REQUIP)	 
Pramipexole (MIRAPEX) 
Rotigotine (NEUPRO) (recalled in 2008)
Apomorphine (APOKYN)
15
Q

What are the COMT inhibitors?

A

Entacapone (COMTAN)
Tolcapone (TASMAR)
Levodopa\carbidopa\entacapone (STALEVO)

16
Q

What are the MAO-B inhibitors?

A

Selegiline (ELDEPRYL, ZELAPAR)

Rasagiline (AZILECT)

17
Q

Name the anticholinergic drugs associated with treating PD

A
Trihexyphenidyl (ARTANE)
Benztropine (COGENTIN)
Procyclidine (KEMADRIN)
Ethopropazine (PARSITAN)
Biperiden (AKINETON)
18
Q

What is the primary reason we give Amantadine?

A

It reduces dyskinesias associated with long-term levodopa therapy.

It’s an influenza A antiviral drug- it has dopaminergic, anticholinergic, and anti-NMDA activities, but it’s effective mechanism of action is unknown still.

19
Q

What is the only surgical treatment that has been approved?

A

Deep brain stimulation–> it is the last line of therapy

20
Q

What is the main drug used as a rescue therapy for “off” symptoms? (“off”-no relief of motor symptoms)

A

Amorphine; fast onset–> use “as needed”

21
Q

What is the net effect of the gain of function mutation in Huntington’s disease?

A

The net effect is the opposite of that in Parkinson’s disease–> decreased GABAergic inhibitory drive from the SNpr and medial globus pallidus onto the ventroanterior and ventrolateral thalamic nuclei (VA/VL).

The end result is increased excitatory input to the motor cortex.

22
Q

Is there any treatment to halt disease progression in Huntingon’s?

A

No- current treatments are targeted to controlling symptoms of depression, anxiety, irritability, paranoia, psychosis

23
Q

What is the only approved therapy for ALS?

A

Riluzole, but it only improves median duration of survival by 60 days

24
Q

What symptoms of Parkinsons are the anticholinergics used to treat and what are their side effects?

A

symptoms-tremor and drooling
side effects-Confusion, impaired memory, hallucinations, typical anticholinergic sx (dry mouth)
Not for use in demented

25
Q

What are some of the side effects of L-DOPA and carvidopa?

A
  • hallucinations
  • dyskinesias
  • on-off phenomenon
  • neuroleptic malignant syndrome (NMS)
  • psychosis possible with chronic use
  • nausea
  • hypotension
  • dizziness
26
Q

Which of the Dopamine agonists must be titrated slowly because of hypotension? What are some other side effects of these drugs?

A
  • the ergot alkaloids; bromocriptine and pergolide
  • pleural effusions, cough, SOB, pulmonary fibrosis
  • cardiac valve regurgitation w/ pergolide
27
Q

Which of the Dopamine agonists can cause compulsive behavior? daytime sleep attacks?

A
  • pramipexole- compulsive behavior

- ropinorole- sleep attacks

28
Q

What are the common side effects of the non-ergot D2 agonists? Ropinirole, Pramipexole, Rotigotine

A

psychosis, nausea, edema

less effective with the motor symptoms of parkinsons

29
Q

Which type of parkinsons drug has side effects of diarrhea, increase in dyskinesias, and urine discoloration?

A
COMT inhibitors (Entacapone, Tolcapone)
**only last 2 hours**
30
Q

Which of the parkinsons drugs has a side effect of fatal hepatotoxicity?

A

Tolcapone only used if entacapone fails

31
Q

What stage of parkinsons are the MAO-B inhibitors (selegiline and rasagiline) used to treat and what are their side effects?

A

treat-mild early parkinsons

side effects-hypotension, GI distress, dyskinesia, and psychosis

32
Q

What other medications can the MAO-B inhibitors (selegiline and rasagiline) not be combined with?

A
  • decongestants
  • dextromethorphan
  • St. John’s wort
  • analgesics
  • methadone
  • tramadol
  • propoxyphene
  • caution with SSRIs, MAO-A inhibitors
33
Q

What is riluzole used to treat and what is its mechanism of action? side effects?

A

-glutamate receptor antagonist
-used to treat ALS
side effects-hepatotoxicity (rare), nausea and diarrhea

34
Q

What is Baclofen used to treat and what is its mechanism of action?

A
  • GABAb receptor agonist-causes loss of spinal motor nerve inputs from the cortex
  • Treats-spasticity
35
Q

What is Tizanidine used to treat and what is its mechanism of action?

A
  • alpha-2 receptor agonist

- Treats- spasticity