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Pharmacology > Week 10 > Flashcards

Week 10 Flashcards

1
Q

What are the characteristic features of Parkinson Disease?

A

tremor
rigidity
bradykinesia
postural instability

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2
Q

What occurs from complications in Parkinson’s?

A

death

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3
Q

What is the pathophysiology of Parkinson’s disease?

A

loss of dopaminergic neurons in the extrapyramidal system, mainly substantia nigra

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4
Q

What percentage of patients on levodopa greater than 5 years will develop motor complications or Parkinson’s?

A

50-90%

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5
Q

What are the two most common motor complications of Parkinson’s?

A

wearing off

on-off effect

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6
Q

How is “wearing off” treated in Parkinson’s?

A

initially treat by dosing more often (shorten dose interval)

later on, add a dopamine agonist

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7
Q

How is “on-off” effect treated in Parkinson’s?

A

treat with rescue apomorphine, or adjust dose/frequency of levodopa

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8
Q

IN Parkinson’s the physical disability is ____ and ____.

A

progressive; unavoidable

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9
Q

initiation of therapy and dosing is _____ ____.

A

highly individualized

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10
Q

What is the mainstay of treatment since 1960s and most effective agent for Parkinson’s?

A

Levodopa (L-dopa)

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11
Q

Does dopamine cross the BBB?

A

NO

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12
Q

Does L-dopa cross the BBB?

A

Yes

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13
Q

What are the significant peripheral adverse effects of Parkinson’s?

A 
dyskinesias
N&V, anorexia
Postural Hypotension
Mental disturbances
Cardiac arrhythmia
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14
Q

What should levodopa (Ldopa) always be administered with?

A

peripheral DDC inhibitor (Carbidopa)

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15
Q

How can GI upset be minimized and help absorption of Levodopa in Parkinson’s?

A

LOW protein meals

Competes for absorption with other amino acids

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16
Q

What is the peripheral dopa decarboxylase (DDC) inhibitor?

A

Carbidopa (Lodosyn)

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17
Q

What are the COMT- Inhibitors? (2)

A

Entacapone (Comtan)

Tolcapone (Tasmar)

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18
Q

What are the MAO-B Inhibitors? (2)

A

Selegiline (Eldepryl, Zelapar)

Rasagiline (Azilect)

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19
Q

What are the 2 ways Carbidopa (Lodosyn) is available?

A

alone-Lodosyn

combo with Levodopa (Sinemet)

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20
Q

What is the dose of carbidopa needed to inhibit peripheral DDC?

A

75-100mg Carbidopa/ daily

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21
Q

How do you usually start treatment with Carbidopa?

A

IR product of 25/100mg (carbidopa/levodopa-Sinemet) TID

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22
Q

What dosage of Levodopa do most patients respond to?

A

750-1,000mg

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23
Q

When can you switch to 25/250mg tab TID of sinemet?

A

After 8 tabs daily of 25/100mg

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24
Q

What is the benefit of Carbidopa (Lodosyn) alone for Parkinson’s?

A

allows greater individualization for patients with advanced Parkinson’s

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25
Q

COMT inhibits are widely distributed…..

A

peripheral and central

26
Q

What are the COMT Inhibitors that precent conversion of Levodopa to 3-O-methyl dopa?

A

Entacapone (Comtan)

Tolcapine (Tasmar)

27
Q

How is Entacapone available?

A

200mg tablet OR Combo with Sinemet (Stalevo)

28
Q

What COMT Inhibitor is dosed as a single drug TID and associated with fatal cases of acute liver failure

A

Talcapone (Tasmar)

29
Q

What COMT inhibitor has limited clinical use?

A

Talcapone (Tasmar)

30
Q

What is the MOA of MAO-B Inhibitors?

A

selective MAO-B inhibition prolongs dopamine effects by inhibiting dopamine metabolism in the brain

31
Q

When are MAO-B Inhibitors used?

A

usually as adjunctive(add-on) therapy in advanced cases of Parkinson’s

32
Q

What is important to remember when using MAO-B Inhibitors?

A

minimize tyramine intake

avoid concomitant use of SSRIs (potential for serotonin syndrome)

33
Q

What medication may delay levodopa therapy by 9 months?

A

early of Selegiline (Eldepryl, Zelapar)

34
Q

Selegiline (Eldepryl, Zelapar) is effective in improving ______ effect by 50-70% but is less effective in improving ______ effects.

A

“wearing off”

“on-off”

35
Q

What medication is more potent inhibition of MAO-B than selegiline?

A

Rasagiline (Azilect)

36
Q

What medication is used as adjunctive to sinemet and useful for treatment of “off” episodes?

A

Safinamide (Xadago)

37
Q

What are the adverse effects of Safinamide (Xadago)?

A

severe htn (at greater than >100mg once daily, greater than recommended dosage)
Hypersexual behavior
Retinal degeneration

38
Q

What medications cross the BBB and stimulate the dopamine (D2) receptor?

A

Dopamine agonists

39
Q

How are dopamine agonists used?

A 
mono therapy (early)
adjunctive (late therapy)
40
Q

What is the improvement of ADLs with dopamine agonists vs levodopa?

A

improve 30% on dopamine agonists vs 40-50% on levodopa

41
Q

When is mono therapy with dopamine agonists more effective?

A

in younger patients (<65 years)

early use may postpone use of levodopa

42
Q

What is the dopamine agonist that is an Ergot derivative?

A

Bromocriptine (Parlodel)

43
Q

What are the dopamine agonist that are a non-ergot derivative?

A

Pramipexole (Mirapex)
Ropinirole (Requip)
Apomorphine (Apokyn)
Rotigotine (Neupro) transdermal

44
Q

What are the increased risk major adverse effects of Bromocriptine (Parlodel)?

A

pericardial fibrosis
cardiac valve fibrosis

rarely used now

45
Q

Pts on pramipexole (Mirapex) AND levodopa showed what outcomes? (3)

A

fewer dyskinesias
fewer “wearing off” effects
fewer motor complications

46
Q

What is the only renally eliminated dopamine agonist?

A

pramipexole (Mirapex)

adjust for CrCl <50

47
Q

Is there a recommended taper for pramipexole (Mirapex)?

A

No

48
Q

How is Ropinirole (Requip) metabolized?

A

hepatically metabolized therefore no dose adjustment for renal dysfunction

49
Q

How is Ropinirole (Requip) discontinued?

A

taper over 7 days

50
Q

What is an injectable dopamine agonist?

A

Apomorphine (Apokyn)

51
Q

What is Apomorphine (Apokyn) FDA approved for?

A

rescue therapy for hypomobility and “off” episodes

52
Q

What is a side effect of Apomorphine (Apokyn)?

A

may cause severe emesis; take with antiemetic

53
Q

What is contraindicated with Apomorphine (Apokyn) and why?

A

Serotonin RAs (ondansetron-Zofran), together can cause severe hypotension & syncope

54
Q

What is the dosage of Apomorphine (Apokyn)?

A

2-6mg SUBCUTANEOUS 3-5x daily PRN

NOT IV!!!

55
Q

What is the only dopamine agonist transdermal patch?

A

Rotigotine (Neupro)

$$$$

56
Q

What was the mainstay treatment for Parkinson’s until the late 1960s?

A

Anticholinergics

57
Q

What are anticholinergics used for Parkinson’s?

A

reserved for resting tremor in early disease, especially if less than 65 years old

58
Q

What are the side effects of anticholinergics?

A 
consitpation
dry mouth
blurred vision
confusion
urinary retention
59
Q

What are the anticholinergics used for Parkinson’s?

A

Benztropin (Cogentin)

Triphenidyl (Artane)

60
Q

What medication is primarily an antiviral agent, found to have anti Parkinson’s activity?

A

Amantadine (Symmetrel)

61
Q

What medication was previously used as early mono therapy but now used as an on add for levodopa induced dyskinesias?

A

Amantadine (Symmetrel)

Pharmacology (17 decks)

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