Parkinson / Alzheimers Flashcards by Brianna Spahn

Classes of Parkinson’s drugs

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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Levodopa vs Dopamine

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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How much levodopa actually enters the brain? Why

1-3%

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

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How can extra cerebral metabolism of Levodopa be reduced?

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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Levodopa MOA, 3 mechanisms

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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Benefits of Carbidopa

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

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Contraindications for Levodopa

Nonselective MAO-I (discontinue use at least 2 weeks before)
H/O malignant melanoma
Narrow angle glaucoma

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

Non selective MAO I

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Levodopa Long Term ADRs

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

By adding a Dopamine Receptor Agonist

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Levodopa Acute ADRs

Nausea
Anorexia
Hypotension

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

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How is levodopa-induced anorexia treated?

Caused by increased concentrations of dopamine.

Treated with peripherally-acting dopamine antagonist (Domperidone)

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

Dopamine Receptor Agonists

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Dopamine Receptor Agonists - Ergot

Both Selectiev D2 receptor agonists

Bromocriptine

Cabergoline

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

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Downside of using Cabergoline for Parkinson’s?

At Parkinson’s dosing level, associated with

Cardiac Valvulopathy

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Dopamine Receptor Agonists - NON Ergot

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

Pramipexole

Dopamine receptor agonist

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

Ropinirole

Dopamine Receptor Agonist

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

Rotigotine

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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

Apomorphine

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

Sudden somnolence - advise not to drive!

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

Restess leg syndrome

ADRs associated with Apomorphine

Dyskinesias
Sweating
Drowsiness
Hypotension

Which MAO (Monoamine Oxidase) primarily metabolizes dopamine

MAO B

MAO B Inhibitors

Selegiline Rasagiline **Selective, irreversible inhibitors of MAO B**

Tyramine and MAO-I's

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.

Dangerous hypertensive combinations for MAO-I's

Decongestants (Phenylephrine, Pseudoephedrine) Stimulants (Amphetamines) Antidepressants with NE Reuptake inhibition (Tricyclic antidepressants) Tramadol

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

Antidepressants (SSRIs, tricyclic) Carbamazapine Tramadol Methadone Antihistamines (Chorpheniramine, Brompheniramine)

Selegiline / Rasagiline Indications

MAO-B I Monotherapy for early Parkinson's Combo w Levodopa - allows reduction of Levo dose - smooths "on-off" fluctuations

Selegiline ADRs

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)

Rasagiline specific drug interactions

** Dose adjust w hepatic impairment** ``` Mepiridine (narcotic) St John's Wort Ciprofloxacin Cyclobenzaprine (muscle relaxant) Dextromethorphan (Robitussin) ```

Catechol - O - Methyltransferase Inhibitors - INDICATIONS

Adjunct therapy for Levodopa | - inhibits metabolism of catecholamines (NE, Dopamine)

COMT Inhibitors

Tolcapone Entacapone

Tolcapone / Entacapone (COMT) ADRs

Related to increased plasma concentrations of Levodopa - Nausea - Anorexia - Hypotension Other ADRs - Orange Urine **Tolcapone - potentially HEPATOTOXIC** AVOID NONSELECTIVE MAO I'S

WHA DA FA IS STALEVO?

Levodopa + Carbidopa + Entacapone

Antiviral drug with Anti Parkinson properties?

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

Amantadine ADRs

Depression Insomnia Agitation Confusion Hallucinations Seizures

Amantadine WARNING

1g dose can be FATAL OD = toxic psychosis **Adjust dose for RENAL insufficiency**

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

Renal insufficiency

Anticholinergics for Parkinsons

Artane (trihexyphenidyl) Cogentin (benztropine)

Artane / Cogentin (anticholinergics) MOA

Improve muscle rigidity and tremor Little effect on bradykinesia

Artane / Cogentin (anticholinergic) ADRs

typical anticholinergic adrs: - dry mouth - urinary retention - constipation - drowsiness - confusion

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

Pimavanserin Selective serotonin inverse agonist

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

Safinamide CI in cirrhosis

American Academy of Neurology - Recommended tx for Parkinson

1. Levodopa or Dopamine Agonist | 2. Selegiline for initial tx of MILD PD

Classes of treatment for Alzheimers

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

Cholinergic Hypothesis

Acetylcholine deficiency contributes to cognitive decline in AD May worsen behavioral issues - Agitation - Apathy - Disinhibition Inhibiting acetycholinesterase = more/longer available acetylcholine

Cholinesterase Inhibitors (ChE-I)

Donepezil - P450 (3A, 2D6) Rivastigmine - associated w weight loss / anorexia Galantamine - also modulates nicotinic receptors

Cholinesterase Inhibitors ADRs

All 3 >> N/V/D Donepezil > muscle cramps, drug interactions (P450) Rivastigmine > Headache, dizziness Galantamine > Sleep disturbances, agitation

NMDA Receptor Antagonist

Memantine ** not clinically relevant** ADRs - diarrhea - dizzines - headache

Antidepressants you could use to help w AD associated depression

Trazodone Sertraline Citalopram