Parkinson's & Huntington's Disease

Front 1

• What neurons die in Parkinson's? What neurotransmitter to they release?
• What neurons die in Huntington's disease? What neurotransmitter do they release?

Back 1

• Substantia Nigra neurons • Dopamne
• Striatal neurons • GABA

Front 2

Symptoms of : unilateral blank face, afected arm in a semi-flexed position w/ tremor, leans to unaffected side are what stage of Parkinson's disease?

Back 2

• Stage 1 of Parkinson's disease.

Front 3

Symptoms of: Bilateral dysfunction, postural changes & shuffling gait is what stage of Parkinson's disease?

Back 3

• Stage 2 of Parkinson's disease.

Front 4

Symptoms of: Pronounced gait disturbance, moderate generalized disability, postural instability, and tendency to fall is what stage of Parkinson's disease?

Back 4

• Stage 3 of Parkinson's disease.

Front 5

Symptoms of: significant disability, limited ambulation w/ assistance is what stage of Parkinson's disease?

Back 5

• Stage 4 of Parkinson's disease.

Front 6

Symptoms of complete invalidism; confined to a bed of chair, cannot walk or stand even w/ assistance is what stage of Parkinson's disease?

Back 6

• Stage 5 of Parkinson's disease.

Front 7

What role does dopamine play in the striatal GABAergic neurons?
What other nerve endings may be lost?

Back 7

• Dopamine released by the substantia nigra counterbalances the excitatory ACh that is also released onto striatal neurons.
• NE nerve endings may also be lost.

Front 8

What drugs can cause Parkinson's like symptoms?

Back 8

• Reserpine & tetrabenazine: deplete biogenic monoamines from their stores
• Haloperidol & phenothiazines block dopamine receptors
• MPTP destroys dopaminergic neurons.

Front 9

What drug is a precursor of dopamine? What enzyme metabolizes it into dopamine? How much is able to enter the brain?

Back 9

• Levodopa (L-dopa)
• Dopa decarboxylase
**Only 1-3% enters the brain across the BBB unaltered**

Front 10

What enzyme catalyzes the rxn: L-dopa --> dopamine?

Back 10

Dopa decarboxylase

Front 11

What are the metabolites of L-dopa?

Back 11

• Homovanillic acid (HVA) & dihydroxyphenylacetic acid (DOPAC)

Front 12

What is an issue with long term L-dopa use?
What is a possible L-dopa toxicity w/ long term use?

Back 12

• ↓ response over time
• Toxicity = supersensitivity ➝ dyskinesia

Front 13

How does Carbidopa work?
Where does it act?
What is the combination L-dopa + Carbidopa drug called?

Back 13

• Carbidopa ⊣ dopa decarboxylase (converts L-dopa ➝ dopamine in the periphery). By preventing this, more L-dopa can cross the BBB
• Carbidopa acts in the periphery
• Sinemet = carbidopa + L-dopa

Front 14

What are the side effects of Levodopa?
What drugs are counterindicated?

Back 14

GI: anorexia, vomiting, & nausea in 80% of pts (*Avoidant antiemetics like phenothiazines because they are dopamine antagonists & can cause EPS)
CV: tachy, ventricular extrasystoles, a-fib (rare), postural hypotension.
• HTN if in the presence of non-specific MAO-I or sympathomimetics.
Behavioral: Depression, anxiety/agitation, insomnia/somnolence, confusion/delusions/hallucinations

Front 15

When is there a risk of HTN when using Levodopa?

Back 15

Levodopa + non-sepcifc MAO-I (or sympathomimetics) can cause HTN

Front 16

Long-term L-dopa therapy causes what side effect in 80% of pts?
How does it commonly manifest?

Back 16

• Dyskinesias
• Choreoathetosis of the face and extremities is the most common presentation.

Front 17

How are drug holidays (from Levodopa) helpful? What are the risks?

Back 17

•  Allows the receptors to upregulate again, ↓ side effects (particularly severe EPS)
• Falling out of favor because of the risk of depression, venous thrombosis, and PE

Front 18

What can the extracerebral metabolism of L-dopa?

Back 18

• Pyridoxine (B6)

Front 19

When is L-dopa contraindicated?

Back 19

• Psychotic patients
• Pts w angle closure glaucoma
• Pts w/ active peptic ulcers
• Pts w/ a history of melanoma

Front 20

What are the advantages of using dopamine agonists over Ldopa?

Back 20

• No enzymatic conversion required, cross BBB w/o competing for transporters
• No potentially toxic metabolites

Front 21

Bromocriptine is what type of drug? MOA?
What is it indicated for?

Back 21

• Bromocriptine is a dopamine agonist (ergot derviative)
• Binds to D2 receptor, is a partial D1 agonist
• 1st line for Parkinsons, also used to tx hyperprolactinemia

Front 22

Pergolide is what type of drug? MOA?
What is it indicated for?

Back 22

• Pergolide is a dopamine agonist (ergot derivative)
• D1 and D2 receptor agonist.
Used for Parkinson's disease, helps pts deal w/ fluctuations when on L-dopa.

Front 23

What two drugs are dopamine agonists and ergot derivatives?

Back 23

• Bromocriptine
• Pergolide

Front 24

What are the GI side affects with dopamine agonists (ergot derivatives)?

Back 24

Bromocriptine & Pergolide (ergot derivatives)
GI: anorexia, vomiting, nausea, constipation, dyspepsia, peptic ulcers, & GERD

Front 25

What are the CV side effects associated w/ Bromocriptine & Pergolide?

Back 25

Bromocriptine & Pergolide (ergot derivatives)
CV: Postural hypotension, arrhythmias

Front 26

What are the misc. side effects associated w/ dopamine agonists (ergot derivatives)?

Back 26

Bromocriptine & Pergolide (ergot derivatives)
Dyskinesias, headache, nasal congestion, ↑ arousal, pulmonary infiltrates, erythromyalgia, vasospasm, & pleural/peritoneal fibrosis

Front 27

What are the psych side-effects associated w/ Bromocriptine & Pergolide?

Back 27

Bromocriptine & Pergolide (ergot derivatives)
Psych: Confusion, hallucinations, delusions
Misc:

Front 28

**What are the contraindications of ergot derivatives?****

Back 28

Bromocriptine & Pergolide (ergot derivatives)
**** Psychotic illness, MI history, PVD, Peptic ulcers ****

Front 29

What is the only pure D2 agonist?

Back 29

Ropinerole

Front 30

Pramiprexole is what type of drug? MOA?
What is it indicated for?

Back 30

Pramiprexole is a dopamine agonist (synthetic, non-ergot derivative)
• Preferential affinity for D3 receptors
• Used as monotherapy for mild Parkinson's, used as combo therapy for severe pts. ↓ L-dopa dose and smooths fluctuations. Some neuroprotective effects.

Front 31

Ropinerole is what type of drug? MOA?
What is it indicated for?

Back 31

Ropinerole is a dopamine agonist (synthetic, non-ergot derivative)
• Pure D2 agonist
• Used as monotherapy for mild Parkinson's, used as combo therapy for severe pts. ↓ L-dopa dose and smooths fluctuations.

Front 32

What are the side effects of the synthetic dopamine agonists?

Back 32

Ropinerole & Pramiprexole are synthetic (non-ergot derivatives) dopamine agonists
• Side effects: Postural hypotension, fatigue, somnolence, peripheral edema, nausea, constipation, dyskinesias & confusion

Front 33

What dopamine agonist must be administered subcutaneously? Why?

Back 33

Apomorphine
• Rapid onset ~ 10 mins, short duration ~ 2hrs.

Front 34

Apomorphine is what type of drug?
What is it indicated for?
What are the side effects?

Back 34

• Dopamine agonist
• Indicated for relief of off-period akinesia
• Side effects: dyskinesias, drowsiness, sweating, hypotension

Front 35

MAO-A metabolizes? MAO-B metabolizes?

Back 35

• MAO-A metabolizes Serotonin & Norepinephrine (*think *A - adrenaline)
• MAO-B metabolizes dopamine (*think* b looks like d)

Front 36

What drugs are selective MAO-B inhibitors?

Back 36

Selegine & Rasagiline

Front 37

Selegine is what type of drug? MOA?
What is it indicated for?

Back 37

• MAO-B inhibitor
• Retards the breakdown of dopamine, enhances & prolongs the effects of L-dopa, reduces response fluctuations, ↓ dose of L-dopa
• Used for Parkinson's

Front 38

Rasagiline is what type of drug? MOA?
What is it indicated for?

Back 38

• MAO-B inhibitor
• Retards the breakdown of dopamine, enhances & prolongs the effects of L-dopa, reduces response fluctuations, ↓ dose of L-dopa
• Used for Parkinson's

Front 39

What are the adverse effects associated w/ Selegine & Rasagline?

Back 39

• Insomnia
• ****Should not be taken by pts on meperidine, TCAs, SSRIs or in combinations w/ non-specific MAO-is**** Can cause serotonin syndrome.

Front 40

Selegine & Rasagline can cause serotonin syndrome when given with what drugs?

Back 40

Selegine & Rasagiline can cause serotonin syndrome when given w/ pts on:
Meperidine
TCAs
SSRIs
non-specific MAO-is

Front 41

What enzyme catalyzes the rxn: L-dopa --> 3-O-methyldopa?

Back 41

Catechol-o-methyl transferase (COMT)

Front 42

What drugs are COMT inhibitors?

Back 42

Tolcapone
Entacapone
Stalevo (L-dopa + carbidopa + entacapone)

Front 43

Which COMT inhibitor inhibits the enzyme both peripherally and centrally?
Which COMT inhibitor inhibits COMT only peripherally?

Back 43

• Tolcapone (*Pays the toll to pass the BBB*)
• Entacapone (only peripheral)

Front 44

Which COMT inhibtor has a longer duration?

Back 44

• Tolcapone (*Pays the toll, can pass the BBB, and can stay longer)

Front 45

What are the adverse effects associated w/ COMT inhibitors?

Back 45

• L-dopa toxicity
• Diarrhea, abdominal pain
• Sleep disturbances
• Orthostatic hypotension
• *orange urine*
• ***Tolcapone is hepatotoxic**** (*Pays the toll, can pass the BBB, can stay longer, and takes a toll on the liver*)

Front 46

What Anti-parkinsonian drug requires monitoring of liver fxn?

Back 46

Tolcapone (*Pays the toll, can pass the BBB, can stay longer, and takes a toll on the liver*)

Front 47

How are ACh drugs used for Parkinsons?

Back 47

• May improve tremor & rigidity

Front 48

Benztropine, Biperiden, Orphenadrine, Procyclidine, & Trihexyphenidyl are?

Back 48

Antimuscarinic drugs that are used in Parkinsons

Front 49

What are the contraindications of Benztropine, Biperiden, Orphenadrine, Procyclidine, & Trihexyphenidyl?

Back 49

Contraindicated in:
• Prostatic hyperplasia
• Obstructive GI disease
• Angle closure glaucoma

Front 50

What area is affected and what is the progression of Huntington's disease?

Back 50

Huntington's disease is a neurological disorder involving the striatal & cortical neurons
Progression: • Chorea
• Metabolic abnormalities
• Cognitive impairment
• Psych symptoms

Front 51

What drugs can help relieve the chorea associated w/ Huntington's disease?
What drugs exacerbate chorea?

Back 51

Drugs that ↓ dopaminergic neurotransmission:
• Reserpine, Tetrabenazine (deplete monoamines) • Olanzapine, risperidone, aripiprazole & clozapine (block dopamine receptors
• Phenothiazines & butyrphenones (useful if refractor to 1st generation neruoleptics)

Drugs that exacerbate chorea are dopamine-like. i.e. L-dopa

Front 52

What is the only approved treatment for ALS?

Back 52

Riluzole

Front 53

What is the MOA of Riluzole? What is it used for? Where is it metabolized?

Back 53

• Inhibitory effect on glutamate release, NMDA antagonist, inactivates VG Na+ channels, interferes w/ intracellular events
• Used for ALS
• Metabolized by CYP1A2

Front 54

What are the side effects of Riluzole? What is it used for?

Back 54

• Weakness, dizziness, GI disorders, ↑ liver enzymes
• Used for ALS

Front 55

In what patients should Riluzole be used cautiously?

Back 55

• In pts w/ hepatic insufficiency

Front 56

What is the most effective drug for Tourettes?

Back 56

Haloperidol