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Pharm > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

Parkinson’s Disease

  • Reduced dopamine
  • Goals: restore dopamine receptor function; inhibition of muscarinic cholinergic receptor
  • No curative treatment
A

Levodopa
Dopamine receptor agonist
MAOIs
Catechol-O-Methyltransferase (COMT) inhibitors
Muscarinic cholinergic receptor antagonist
Amantadine

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2
Q

Levodopa

- First line for Parkinson’s

A
  • Prodrug (immediate metabolic precursor of dopamine, Levodopa crosses BBB while dopamine can’t)
  • MOA: restoration of synaptic concentration of dopamine; activation of post-synaptic D2 receptors (indirect pathway) and D1 receptors (direct pathway)
  • ADR: Dyskinesias (80% of long term use, Choreiform movements, dose related, more in young pt); “ON (improved mobility, marked dyskinesia)- OFF (marked akinesia)” effect (fluctuation in clinical response to levodopa, fixed when taken with dopamine receptor agonist)
  • ACUTE ADR (related to increased peripheral [dopamine]: NAUSEA/anorexia (treat with peripherally acting dopamine antagonist)/hypotension
  • OTHER ADR: confusion, insomina, nightmares, schizophrenic-like syndrome (delusions and hallucinations)
  • CONTRAINDICATIONS: non selective MAOI (d/c >2weeks before starting levodopa); h/o malignant melanoma; narrow angle glaucoma
  • Monitor LFTs
  • Best results obtained in first few yrs of treatment
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3
Q

Carbidopa

A
  • Inhibits dopa decarboxylase
  • Prevents peripheral conversion of levodopa to dopamine (allows levodopa to cross BBB)
  • Increases bioavailability
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4
Q

Dopamine Receptor Agonist

A
  • ADR: anorexia, N/V, hypotension, cardiac arrhythmias, headache, confusion, hallucinations, sedation, pulmonary fibrosis
  • Lower incidence of response fluctuation and dyskinesia than long term levodopa
  • Use before levodopa or w/ low dose of carbidopa/levodopa
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5
Q

Ergot Dopamine Receptor Agnoist

A

Bromocriptine (Parlodel)

Cabergoline (Dostinex)

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6
Q

Bromocriptine (Parlodel)

A
  • MOA: Selective D2 receptor agnoist
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7
Q

Carbergoline (Dostinex)

A
  • MOA: Selective D2 receptor agonist
  • Longer acting than bromocriptine
  • associated with cardiac valvulopathy when used at parkinson’s dosing
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8
Q

NonErgot Dopamine Receptor Agonists

A

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

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9
Q

Pramipexole (Mirapex)

- Advanced Parkinson’s dz

A
  • MOA: D3 receptor (also D2/D4)
  • USE: restless legs syndrome
  • Possibly neuroprotective- scavenges H2O2
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10
Q

Ropinirole (Requip)

A
  • MOA: D2 receptor agnoist
  • effective as monotherapy with mild dz
  • USE: restless legs syndrome
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11
Q

Rotigotine (Neupro)

A
  • Transdermal patch
  • Sudden somnolence (asleep for driving, eating, talking)
  • NO driving!
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12
Q

Apomorphine

A
  • MOA: Potent D1/D2 agnoist
  • SubQ injection
  • USE: temp relief of “off” periods of akinesia
  • ADR: dyskinesias, drowsiness, sweating, hypotension)
  • short period of effectiveness
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13
Q

What happens if you give metoclopramide to Parkinson’s pt?

A

Metoclopramide: dopamine agonist

- increase parkinson’s symptoms

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14
Q

Monoamine Oxidase Inhibitors (MAOIs)

A
  • MAO-A: primarily metabolizes NE and 5-HT

- MAO-B: primarily metabolizes dopamine

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15
Q

MOA-A

A

Tyramine (soy sauce, beens, beer)…

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16
Q

MAO-B

A

Selegiline
Rasagiline
- selective, irreversible inhibitors of MAO-B

17
Q

Selegiline

A
  • MOA: MAO-B inhibitor
  • USE: early Parkinson’s as monotherapy or in combination with levodopa; helps reduction in levodopa dose or may smooth the “on-off” fluctuations
  • ADR: blocks MAO-A at high doses (hypertensive crisis due to peripheral accumulation of NE); fatal hyperthermia (conjunction with meperidine, cocaine, fluoxetine)
18
Q

Rasagiline (Azilect)

A
  • Irreversible MAO-B inhibitor
  • USE: early parkinson’s and adjunct with levodopa
  • Extensive liver metabolism (CYP1A2)
  • DRUG INTERACTIONS: meperidine, dextromethorphan, St. John’s wort, cyclobenzaprine, ciprogloxacin
  • HEPATIC adjust
19
Q

Catechol-O-Methyltransferase (COMT) Inhibitors

A
  • COMT: liver, kidney/ heart, lung, smooth and skeletal muscles
  • Metabolizes catecholamines (dopamine, NE, EPI)
  • Metabolizes Levodopa to 3-OMD in brain and periphery
  • MAO and COMT both metabolize catecholamines: avoid non selective MAOIs with COMT (MAO-BI generally OK)
  • Watch liver
20
Q

Tolcapone (TASMAR) and Entacapone (Comtan)

  • INCREASE availability of Ldopa
  • Adjunctive therapy with Levodpa
A
  • Selective COMT inhibitors: diminish peripheral metabolism of levodopa
  • USE: may reduce “on-off” flunctuations
  • ADR: increase [Levodopa] (dyskinesias, N, confusion); D/abd pain, orthostatic hypotension, sleep disorders, orange urine discoloration
  • Tolcapone ADR: POTENTIALLY HEPATOTOXIC
  • Entacapone: P450 inhibitor at high doses
  • Taper dosing for discontinuation
21
Q

Stalevo (levodopa/carbidopa/entacapone)

A
  • Combination drug
22
Q

Amantadine (Symmetrel)

A
  • Antiviral drug w/ anti-Parkinsonian properties
  • MOA unclear; potentiates dopaminergic function (modifying synthesis, release, or reuptake of dopamine)
  • USE: best in advanced PD w/ dyskinesias
  • Less effective than levodopa/bromocriptine
  • ADR: Primarily CNS (restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, confusion, seizures); HA, edema, postural hypotension, HF, GI disturbances
  • Overdose= acute toxic psychosis
  • RENAL adjust
23
Q

Anticholinergics

- Mediate cholinergic tremor

A
  • Muscarinic receptors (localized to striatal neurons): may cause presynaptic inhibition of dopamine release
  • Dopamine deficiency in the striatum augments the excitatory cholinergic system
  • blockade of this system by anticholinergic helps alleviate motor dysfunction
24
Q

Trihexphenidyl (Artane) and Benztropine (Cogentin)

A
  • USE: for pts taking neuroleptics as anti-dopaminergic properties of these drugs antagonize effects of levodopa, improve muscle rigidity and tremor (little effect on bradykinesia)
  • ADR: Atropine like (dry mouth, inability to sweat, impaired vision, urinary retention, constipation, drowsiness, confusion)
25
Q

Parkinson’s Treatment Recommendations

A
  1. Selegiline for initial mild PD treatment
  2. Levodopa or Dopamine agonist
    - Levodopa improves motor disability (safe, does not accelerate dz progression)
    - Dopamine agonist better to decrease risk of motor complications
  3. Alternative therapies with some evidence: exercise, speech therapy
  • no improvement with Vit E

Pharm (9 decks)

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