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Neuro II Drugs > Movement Disorders > Flashcards

Movement Disorders Flashcards

1
Q

Levodopa (D2) - PD

A
  • enter via LAT (note: dopamine can’t cross BBB)
  • decarboxylated to dopamine; 1-3% enters brain unaltered
  • rapidly absorbed from SI (peaks at 1-2 hrs; half life 1-3 hrs)
  • “wearing off” phenomenon - long term treatment
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2
Q

Levodopa + Carbidopa (dopa decarboxylase inhibitor)

A
  • decrease peripheral metabolism
  • increase plasma levels
  • increase half life
  • increase levodopa availability to enter brain
  • reduced daily requirement for levodopa by 75%
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3
Q

Adverse effects - Levodopa

A

GI - anorexia, nausea, vomiting (chemo receptor trigger zone in brain stem activated) in 80%
CV - postural hypotension, get HTN with LARGE DOSES (or in combo with MAO inhibitor)
rare - cardiac arrhythmias (inc peripheral catecholamine)
Dyskinesis - choreoathetosis of face + extremities in 80%
Behavior - depression, anxiety, hallucinations, confusion etc.

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4
Q 
Antipsychotic drugs 
(due to adverse effects of levodopa)
A
  1. Clozapine
  2. Olanzepine
  3. Quetiapine
  4. Risperidone
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5
Q

“On-off phenomenon” - levodopa

A

Fluctuation due to:
1. Timing of day (WEARING OFF phenomenon)
2. Unrelated to dose timing (ON-OFF phenomenon)
Severe OFF periods –> APOMORPHINE

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6
Q

Apomorphine

A
  • D2 agonist Rc in caudate/putamen
  • give subcutaneously (only one that’s injectable)
  • quick/temp relief when experiencing “off” periods
    Adverse effect - nausea, sweating, hypotension, drowsiness
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7
Q

If giving Apomorphine, what anti-memetic should you pretreat patient with?

A

Trimethobenzamide (helps with the adverse effects experienced by Apomorphine)

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8
Q

Levodopa contraindications

A
  1. If given with MAO-A inhibitor –> HTN crisis

2. Psychosis, closed-angle glaucoma (OK with open-angle tho), melanoma, peptic ulcer/GI bleed

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9
Q

Bromocriptine

A
  • D2 Rc agonist; alkaloid
  • used for endocrine disorders too
  • high 1st pass metabolism - CYP 3A4
  • 28% bioavailability
    Adverse effect - digital vasospasm, peripheral edema, heart arrhythmia; Retroperitoneal fibrosis
    Contraindications - peripheral vascular disease
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10
Q

Pramipexole

A
  • D3 Rc agonist
  • treats RLS
  • 90% excreted unchanged
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11
Q

Ropinirole

A
  • D2 Rc agonist
  • treats RLS
  • metabolized by CYP 1A2 in liver
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12
Q

Dopamine agonists - Adverse effects/contraindications

A

GI - constipation, dyspepsia, vomiting, nausea
CV - postural hypotension,
Dyskinesis - similar to levodopa
Mental - hallucinations, confusion, MORE SEVERE than levodopa
Misc. - headache, nasal congestion, pulmonary infiltration, inc arousal
Contraindications - psychosis, MI, peptic ulcer

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13
Q

MAO types

A
  1. MAO-A = metabolizes NE + serotonin
  2. MAO-B = metabolizes phenylethylamine + benzylamine
  3. MAO-A + MAO-B = dopamine + tryptamine
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14
Q

MAO inhibitors

A
  1. Selegiline

2. Rasagiline

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15
Q

Selegiline (deprenyl)

A
  • IRREVERSIBLE
  • MAO-B inhibition (MAO-A inhibition at HIGH doses)
  • slows dopamine breakdown
    Contraindications - meperidine, tricyclic depressants, serotonin reuptake inhibitors (can get serotonin syndrome!!)
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16
Q

Rasagiline

A
  • IRREVERSIBLE
  • MAO-B inhibition (more potent)
  • neuroprotective
  • early trt of PD
  • BUT combined levodopa and nonselective MAO inhibitor can lead to HTN crisis!!
17
Q

COMT inhibitors

A

metabolizes levodopa –> 3-O methyldopa
1. Tolcapone (CENTRAL + PERIPHERAL effects) - increase in liver enzyme levels causing hepatotoxicity
2. Entacapone (PERIPHERAL effects only)
Side effects of both- orange discoloration of urine, diarrhea, abdominal pain, sleep disturbances

18
Q

Amantadine

A
  • MOA unknown
  • short lived benefits
  • used in PD
  • livedo reticularis - vascular condition: purplish mottled discoloration of skin (legs usually)
  • can cause hallucinations, restlessness, confusion, GI/heart failure
19
Q

mAcH Rc antagonists

A

Improve tremor/rigidity but little effect on bradykinesia

  1. Benztropine
  2. Biperden
  3. Orphenadrine
  4. Procyclidine
  5. Trihexyphenidyl
20
Q

Other disorders - Tremor

A
  • Metoprolol, Propranolol: b1
  • Primidone: anti-epileptic drug
  • Topirimate: serotonin Rc agonist (Broad spectrum drugs)
  • Alprazolam: benzodiazepines
  • Botulinum toxin A: intramuscular injection
21
Q

Other disorders - Huntington

A
  • GABA, GAD, choline acetyltransferase decreased in basal ganglia
    1. Reserpine - IRRVERSIBLE - block vesicular monoamine transporter/deplete dopa
    2. Tetrabenazine - REVERSIBLE (shorter duration) - block VMT/deplete dopa
    3. Olanzapine
    4. Perphenazine - Phenothiazines
    5. Haloperidol - Butyrophenones
    6. Fluoxetine - depression + irritability
    7. Carbamazepine - depression (generalized onset + partial onset)
22
Q

Other disorders - Tics

A
  1. Antipsychotics - Tetrabenzaine, Haloperidol, Pimozide (cause extrapyramidal syndrome, weight gain)
  2. Alpha adrenergic - Clonidine, guanfacine
  3. Injection of botulinum toxin A
23
Q

Other disorders: RLS

A
  1. 1st line trt - Pramipexole, Ropinirole

2. Dopamine agonists - correction of coexisting iron deficiency anemia corrects this too

24
Q

Other disorders - ALS

A

Riluzole - inhibits glutamate, blocks NMDA and kainite-type glut Rc and inhibits VG Na channels

25
Q

Other disorders - Wilson disease

A

Copper metabolism disorder - dec ceruloplasmin, inc Cu in brain and viscera, hepatic/neurological dysfunction
1. Penicillamine - (chelating) forms complex with Cu –> excreted
Adverse effects - nausea, vomiting, nephrotic syndrome, optic neuropathy, blood disorders, myasthenia
2. Potassium disulfide - decrease absorption of Cu (give with 1.)
3. Others - Trientine (chelating), Zinc acetate (fecal excretion of Cu), Zinc sulfate (fecal excretion of Cu)

Neuro II Drugs (7 decks)

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