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Pharm Test 2 > Parkinson's > Flashcards

Parkinson's Flashcards

1
Q

Parkison’s

S/S

A
  • Bradykinesia/akinesia
  • Tremor (pill-rolling)
  • Rigidity (cogwheel)
  • Impairment of postural balance

*mask face, shuffling gait, autonomic, weight-loss, anorexia, depression

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2
Q

Parkinson’s

Pathology

A
  • Dop neuron degeneration
  • > 65 years
  • more cells lost - worse disease
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3
Q

Parkinson’s

CNS pathway

A

Nigrostriatal projection DEGENERATE

*substantia nigra –> Striatum

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4
Q

Parkison’s

problem with replacing dopamine

A

Mesocorticolimbic = Ventral tegmental –> nucleus accumbens

Too much = psychosis

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5
Q

Parkison’s

Smoking

A

Neuroprotective

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6
Q

GABA pathway

A

Nigrostriatal = Dopamine (D2) inhibit GABA DIES

Cholinergic = Ach (M) excitatory

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7
Q

MPTP

A

Goes to MPP+, selectively destroys Substantia Nigra neurons

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8
Q

Selegiline

A

Stops development of parkinson in monkeys

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9
Q

Suspected source of parkinson’s?

A

Pesticides, chemical in (country?)

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10
Q

Pharm target =

A

Imbalance between striatal cholinergic + dopaminergic activity

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11
Q

Pharm strategies

A
  • Dopa replacement
  • Enzyme inhibition
  • MAO-B inhibition
  • Up Dopa release, block reuptake
  • stim dopa receptor
  • anticholinergic (m)
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12
Q

Dopamine replacement

A
  • L-DOPA levodopa (dopa precursor)
  • Use Aromatic amino acid transporter
  • 95% lost in periphery

Dopa can’t cross

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13
Q

Peripheral Dopa Toxicity

A
  • Nausea (CTZ)
  • Cardiac palpitations + arrythmia (b-agonist)
  • Postural HypoTN (vascular DA receptor)
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14
Q

DOPA

CNA toxicity

A
  • Psychotic (accumbens, limbic system)
  • Dyskinesias (striatum)
  • On-off phenomenon (variable CNS metabolism)
    • -Off = dystonia
    • -ON = good but dyskenesia
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15
Q

Control on -off phenomenon

A

Enzyme inhibition =
COMT
MAO-B

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16
Q

L-DOPA

Contraindications

A
  • Psychosis
  • Melanoma
  • Narrow angle glaucoma

look at slides for info

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17
Q

L-Dopa

Rx interaction

A
  • Non-selective MAO inhibitors - gets MAO-A (selective for MAO-B ok)
  • Vitamin B6 (up peripheral metab=More S.E.)
  • anti-psycs (work against each other)
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18
Q

B6 effect on L-DOPA

A

Ups levodopa conversion to DA peripheral

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19
Q

L- DOPA

Clinical problems

A
  • Tolerance
  • Gradually degenerating CNS nerves = can’t convert L-Dopa
  • Limited effectiveness (1/3)
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20
Q

L-DOPA best helps with these symptoms

A

Bradykinesia

Akinesia

21
Q

Use L-Dopa in beginning?

A

Physicians prefer to start later (tolerance)

22
Q

Cardidopa

Mech

A

Inhibits l-aad enzyme which converts L-dopa to peripheral Dopa = more goes in CNS

*COMT up (shunt) = inhibit too

23
Q

Inhibiting COMT

A
  • Tolcapone - ALSO IN CNS (helps w/ ON OFF SYNDROME )

* Entacapone

24
Q 
Enzyme inhibitors 
(cardidopa, -capone)

Advantages

A
  • reduce L-dopa dose
  • peripheral side effects reduces
  • on-off reduced
25
Q 
Enzyme inhibitors
(cardidopa, -capone)

Disadvantages

A

CNS toxicity of L-dopa

26
Q 
Enzyme inhibitors
(cardidopa, -capone)

SIde effects

A

Due to up DA

27
Q

Rx preparations

A
  • L-DOPA
  • Carbidopa
  • Sinemet (cardidopa + L-DOpA)

COMT inhibitor

  • entacapone (no in CNS
  • tolcapone (liver toxicity)
28
Q

Nausea caused by

A

Peripheral Dopa ????

29
Q

How to inhibit MAO-B

A

Selegine

Rasagiline

30
Q

Inhibiting MAO

Mech

A

MAO-B predominate form in striatum

MAO-A = don’t touch - need to handle catecholamines (avoid HTN)

31
Q

Selegiline

A

May reduce neurotoxic metabolite

*Eldepryl

32
Q

Nicotine

A

Neuroprotective + releases DA

33
Q

MAO-B

S.E.

A
  • UP CNS dopa effects
  • Oral selegiline causes amphetamine metabolism
  • no w/ non-selective MAO inhibitor
34
Q

Direct D2 stimulators

A

No dopamine releasing neuron

  • Ropinirole
  • Pramipexole
  • Bromocriptine
35
Q

Direct D2 stimulator

On-off

A

NO ON-OFF

Skipping neuron

36
Q

D2 ags

Use

A
  • L-dopa dose reduced
  • No on off
  • Refractory L-dopa patient
  • Used before L-dopa
37
Q

D2 agonist

Contraindications

A
  • Psychosis
  • recent MI, PV dz
  • peptic ulcer (N/V)
38
Q

Enhance DA release + inhibit reuptake

A

*Amantadine

Need to have neurons to release dopa

39
Q

Amantadine

Uses

A
  • initial therapy
  • LESS bradykinesia, rigidity, tremor
  • L-dopa/cardidopa fluctuations/dyskinesias
  • NMDA receptors - improve cognition
40
Q

Amantadine

S.E.

A

Mild

OD = toxic psychosis

41
Q

Antimuscarinics

Rx

A

Benztropine

Trihexyphenidyl

42
Q

Antimuscarinic

Uses

A
  • combo w/ L-dopa
  • mild parkison’s (tremor only)
  • better on tremor and rigidty than bradyinesia
43
Q

Antimuscarinics

contraindications

A
  • Prostatic hypertrophy
  • Obstructive GI disease
  • Narrow angle glaucoma
44
Q

Early non-pharm treatment

A

Lifestyle / exercise

45
Q

For Mild symptoms Tx/ initial tx

A
  • MAO-B inhibtors
  • Amantadine
  • Anticholinergics

Younger = D2 agonist

46
Q

for Moderate symptoms

A

Levodopa

D2 agonist

47
Q

Antimuscarinic

S.E.

A

Peripheral = dry mouth, blurred vision, Blurred vision, mydriasis, urinary retention, nausea

Central = Drowsiness, mental slowness, Inattention, Restlessness

48
Q

D2 agonist

S.E

A

Peripheral = nausea (CTZ), hypoTN

CNS =
Dyskinesia (less than L-DOPA)
Psychosis (more than L-DOPA)

Pharm Test 2 (13 decks)

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