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PHARM II, QUIZ 4 > Parkinson / Alzheimers > Flashcards

Parkinson / Alzheimers Flashcards

1
Q

Classes of Parkinson’s drugs

A

Levo / Carbi dopa

Dopamine Receptor Agonists

Monoamine Oxidase Inhibitors (MAO-I)

Catechol O Methyltransferase Inhibitors (COMT)

Muscarinic Cholinergic Receptor Agonist

Amantadine

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2
Q

Levodopa vs Dopamine

A

Levodopa is an immediate PRECURSOR of Dopamine

Levo crosses the BBB, but Dopamine does not

If Levo is metabolized to Dopamine, it will not cross BBB

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3
Q

How much levodopa actually enters the brain? Why

A

1-3%

Extracerebral metabolism from Levodopa to Dopamine (which can’t cross bbb)

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4
Q

How can extra cerebral metabolism of Levodopa be reduced?

A

By administering Carbidopa along with Levodopa.

Carbidopa is a peripheral decarboxylase inhibitor - so it inhibits the metabolism of levodopa to dopamine

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5
Q

Levodopa MOA, 3 mechanisms

A

Restores synaptic concentrations of dopamine

Activates post-synaptic D2 receptors
(which promotes voluntary movement via indirect pathway)

Activates post-synaptic D1 receptors
(which promotes voluntary movement via direct pathway)

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6
Q

Benefits of Carbidopa

A
  1. Increases bioavailability / allows more BBB cross of Levodopa by inhibiting metabolism into dopamine (decarboxylase inhibitor)
  2. Limits peripheral side effects of Levodopa bc allows for lower dose
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7
Q

Contraindications for Levodopa

A
  1. Nonselective MAO-I (discontinue use at least 2 weeks before)
  2. H/O malignant melanoma
  3. Narrow angle glaucoma
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8
Q

Which parkinson’s drug must be discontinued at least 2 weeks before starting Levodopa?

A

Non selective MAO I

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9
Q

Levodopa Long Term ADRs

A

Dyskinesias

  • 80% occurrence in long term levo therapy
  • higher dose = increased risk
  • more frequent in younger pts

“On-Off” effect

  • fluctuations in plasma concentration
  • off = marked akinesia
  • on = improved mobility but marked dyskinesia
  • improved w adding a dopamine agonist*
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10
Q

How can On-Off fluctuations of Levodopa effect be smoothed out?

A

By adding a Dopamine Receptor Agonist

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11
Q

Levodopa Acute ADRs

A

Nausea
Anorexia
Hypotension

Neuro stuff:
Confusion
Insomnia
Nightmares
Schizo-like syndrome, delusions and hallucinations
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12
Q

How is levodopa-induced anorexia treated?

A

Caused by increased concentrations of dopamine.

Treated with peripherally-acting dopamine antagonist (Domperidone)

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13
Q

Class of Parkinson’s drugs which can have a lower incidence of response fluctuation and dyskinesia than levodopa

A

Dopamine Receptor Agonists

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14
Q

Dopamine Receptor Agonists - Ergot

A

Both Selectiev D2 receptor agonists

Bromocriptine

Cabergoline

  • longer acting than Bromo
  • At Parkinson’s dosing, associated w cardiac valvulopathy
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15
Q

Downside of using Cabergoline for Parkinson’s?

A

At Parkinson’s dosing level, associated with

Cardiac Valvulopathy

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16
Q

Dopamine Receptor Agonists - NON Ergot

A

Pramipexole
- D3 receptor, advanced Parkinsons, restless leg

Ropinirole
- D2 receptor, mono therapy mild Parkinsons, restless leg

Rotigotine
- Transdermal patch, sudden somnolence

Apomorphine
- D1/D2 receptor, SubQ injection for “off” periods

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17
Q

Which Parkinson’s treatment is a D3 receptor agonist and used to treat advanced disease?

A

Pramipexole

Dopamine receptor agonist

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18
Q

Which Parkinson’s treatment is a D2 receptor agonist and used as a mono therapy for mild disease?

A

Ropinirole

Dopamine Receptor Agonist

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19
Q

Which Parkinson’s treatment is a transdermal patch and associated with sudden somnolence?

A

Rotigotine

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20
Q

Which Parkinson’s treatment is a D1/D2 receptor agonist, very potent but short period of effectiveness / used to smooth out “off” periods of akinesia

A

Apomorphine

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21
Q

What would you need to warn a patient about when prescribing Rotigotine?

A

Sudden somnolence - advise not to drive!

22
Q

What other neuro problem can Pramipexole and Ropinirole be used to treat?

A

Restess leg syndrome

23
Q

ADRs associated with Apomorphine

A

Dyskinesias
Sweating
Drowsiness
Hypotension

24
Q

Which MAO (Monoamine Oxidase) primarily metabolizes dopamine

A

MAO B

25
Q

MAO B Inhibitors

A

Selegiline

Rasagiline

Selective, irreversible inhibitors of MAO B

26
Q

Tyramine and MAO-I’s

A

At high doses, MAO-B Inhibitors taken with tyramine foods (wine, cheese, sausage etc) can cause a hypertensive crises - because MAO’s are responsible for breaking down excess NE released by tyramine.

27
Q

Dangerous hypertensive combinations for MAO-I’s

A

Decongestants (Phenylephrine, Pseudoephedrine)

Stimulants (Amphetamines)

Antidepressants with NE Reuptake inhibition
(Tricyclic antidepressants)

Tramadol

28
Q

Potentially lethal combinations with MAO-I’s - hyperthermia, serotonin syndrome

A

Antidepressants
(SSRIs, tricyclic)

Carbamazapine

Tramadol
Methadone

Antihistamines
(Chorpheniramine, Brompheniramine)

29
Q

Selegiline / Rasagiline Indications

A

MAO-B I

Monotherapy for early Parkinson’s

Combo w Levodopa

  • allows reduction of Levo dose
  • smooths “on-off” fluctuations
30
Q

Selegiline ADRs

A

MAO-B I, selective for Brain

so unlikely to produce peripheral tyramine problems (hypertension crisis)

Fatal hyperthermia when administered in conjunction with:

  • Cocaine
  • Mepiridine (narcotic)
  • Fluoxetine (SSRI)
31
Q

Rasagiline specific drug interactions

A

** Dose adjust w hepatic impairment**

Mepiridine (narcotic)
St John's Wort
Ciprofloxacin
Cyclobenzaprine (muscle relaxant) 
Dextromethorphan (Robitussin)
32
Q

Catechol - O - Methyltransferase Inhibitors - INDICATIONS

A

Adjunct therapy for Levodopa

- inhibits metabolism of catecholamines (NE, Dopamine)

33
Q

COMT Inhibitors

A

Tolcapone

Entacapone

34
Q

Tolcapone / Entacapone (COMT) ADRs

A

Related to increased plasma concentrations of Levodopa

  • Nausea
  • Anorexia
  • Hypotension

Other ADRs
- Orange Urine

Tolcapone - potentially HEPATOTOXIC

AVOID NONSELECTIVE MAO I’S

35
Q

WHA DA FA IS STALEVO?

A

Levodopa + Carbidopa + Entacapone

36
Q

Antiviral drug with Anti Parkinson properties?

A

Amantadine!

MOA unclear

Less effective than others - best for advanced Parkinsons w dyskinesias (from other drugs)

37
Q

Amantadine ADRs

A

Depression
Insomnia
Agitation

Confusion
Hallucinations
Seizures

38
Q

Amantadine WARNING

A

1g dose can be FATAL

OD = toxic psychosis

Adjust dose for RENAL insufficiency

39
Q

Under what condition would you need to adjust the dose of Amantadine

A

Renal insufficiency

40
Q

Anticholinergics for Parkinsons

A

Artane (trihexyphenidyl)

Cogentin (benztropine)

41
Q

Artane / Cogentin (anticholinergics) MOA

A

Improve muscle rigidity and tremor

Little effect on bradykinesia

42
Q

Artane / Cogentin (anticholinergic) ADRs

A

typical anticholinergic adrs:

  • dry mouth
  • urinary retention
  • constipation
  • drowsiness
  • confusion
43
Q

Drug that can be used to reduce hallucinations/ delusions in patients with PD psychosis

A

Pimavanserin

Selective serotonin inverse agonist

44
Q

NEW drug indicated for patients taking levodopa / carbidopa and having “off” episodes

A

Safinamide

CI in cirrhosis

45
Q

American Academy of Neurology - Recommended tx for Parkinson

A
  1. Levodopa or Dopamine Agonist

2. Selegiline for initial tx of MILD PD

46
Q

Classes of treatment for Alzheimers

A
  1. Cholinergic agents /ACh-esterase Inhibitors
  2. NMDA Receptor Agonists (little effectiveness)
  3. Antidepressents
  4. Non-pharmacologic (behavioral, exercise, recreation),
47
Q

Cholinergic Hypothesis

A

Acetylcholine deficiency contributes to cognitive decline in AD

May worsen behavioral issues

  • Agitation
  • Apathy
  • Disinhibition

Inhibiting acetycholinesterase = more/longer available acetylcholine

48
Q

Cholinesterase Inhibitors (ChE-I)

A

Donepezil - P450 (3A, 2D6)

Rivastigmine - associated w weight loss / anorexia

Galantamine - also modulates nicotinic receptors

49
Q

Cholinesterase Inhibitors ADRs

A

All 3&raquo_space; N/V/D

Donepezil > muscle cramps, drug interactions (P450)

Rivastigmine > Headache, dizziness

Galantamine > Sleep disturbances, agitation

50
Q

NMDA Receptor Antagonist

A

Memantine

** not clinically relevant**

ADRs

  • diarrhea
  • dizzines
  • headache
51
Q

Antidepressants you could use to help w AD associated depression

A

Trazodone

Sertraline

Citalopram

PHARM II, QUIZ 4 (3 decks)

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