Parkinson's - Block 1

Question 1

What is the problem with PD?

Answer 1

Low dopamine from low producing neurons

-> less instructions to the brain -> motor symptoms

Question 2

What is the mechanism of dopamine?

Answer 2

1. Produced by neurons in the substantia nigra
2. Activation of DR signals the motor cortex
3. Smooth, coordinated function of body muscles and movement

*Dopamine gives the brain instructions to move

Question 3

What are the sx of PD?

Answer 3

Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability

Question 4

What is the most common sx of PD? Most common type?

Answer 4

Tremor; pill rolling

Occurs at rest

Question 5

How occurs during rigidity?

Answer 5

Stiffness and pain with alterations of motion

Question 6

What is Akinesia/Bradykinesia?

Answer 6

Absence or slowness of movement and difficulty to move
* Decreased dexteritity

Question 7

What is postural instability?

Answer 7

1. Shuffling walk
2. Stooped posture
3. Unable to recover balance
4. Risk of falling

Question 8

Other motor sx of PD?

Answer 8

Falls
Freezing
Dysphagia
Micrographia
Slurred speech
Drooling
Reduced voice volume
Dystonia
Difficulty rising from a seated position

Question 9

Non motor sx of PD?

Answer 9

Hypotension
Bladder dysfunction
Sexual dysfunction
Sleep disturbances
Depression
Anxiety
Psychosis/hallucinations
Cognitive impairment
Decreased sense of smell

Question 10

How do we diagnose PD?

Answer 10

1. Presence of bradykinesia and at least 1 other TRAP symptom
2. Other conditions have been ruled out
3. Presence of 3 supportive findings:
   * Asymmetry of motor features
   * Unilateral onset
   * Resting tremor
   * Progressive disorder
   * Responsive to dopaminergic therapy

Question 11

What does it feel like for a PD patient?

Answer 11

Put yourself in the patient’s shoes.

Question 12

What can we do about PD?

Answer 12

Replace dopamine

Question 13

How do we replace dopamine? Tx for PD

Answer 13

Give dopamine (precursor): Sinemet
Give something to preserve dopamine: COMT Inhibitors, MAO-B Inhibitors
Give something that acts like dopamine: Dopamine Agonists
Give drugs to treat specific symptoms: Anticholinergics, Amantadine, Adenosine A2A Antagonists

Question 14

What are the first line agents for PD?

Answer 14

1. MAO-B Inhibitors
2. Dopamine Agonists
3. Sinemet

Question 15

Sinemet

Generic, Indication, ADR, CI, Counseling

Answer 15

Carbidopa-Levodopa
Indication: Bradykinesia and rigidity are predominant, patient is elderly or has cognitive impairment
* prevents peripheral conversion of levodopa

ADR: GI, orthostasis, dz, psych, dark body fluids, dyskinesias, wearing off phenomenon
CI: MAOI use within 14 days, narrow angle glaucoma
Counseling: Do not DC abruptly
* Best absorbed on an empty stomach (avoid iron and high protein foods)
* Don’t crush or chew
* Dry powder levodopa inhaler may be used for breakthrough symptoms

Question 16

What is the on/off phenomenon?

Answer 16

Fluctuations in movement sx:
* On: good movement
* Off: poor movement

Wearing off is the worsening sx prior to the next dose of med
* Short half-life of levodopa and decline in the ability of the brain to store dopamine

Question 17

What are the tx for wearing off sx?

Answer 17

• Give Sinemet more frequently (reduce dosing interval)
• Give IR formulation on empty stomach (consistent absorption)
• Add COMT inhibitor, MAO-B inhibitor, or DA to extend action of Sinemet
• Add ER formulation

Question 18

What is peak dose dyskinesias?

Answer 18

1. Involuntary movements that occur in patients taking levodopa
2. Associated with peak dose of dopamine
3. Tardive dyskinesia

Question 19

What is the tx for peal dose dyskinesias?

Answer 19

Lowering levodopa dose -> suboptimal control of PD

Question 20

What are your dopamine agonsits?

Answer 20

Ropinirole (Requip)
Pramipexole (Mirapex)
Rotigotine (Neupro)
Apomorphine (Apokyn)
Bromocriptine (Parlodel)

Question 21

Dopamine Agonists

Indication, ADR, CI, COunseling

Answer 21

Indication: initial, add on therapy
* Younger patients
* May be added to Sinemet to help with wearing off
* RLS
* Pramipexole may also improve depression
* Less risk of motor complications compared to Sinemet

ADR: GI, psych, orthostasis, drowsiness, obsessive behaviors
CI: Bromocriptine – avoid if allergic to ergots
* Neupro – avoid if sensitive to sulfites
* Apomorphine: Do not use with SHT3 antagonists (ondansetron, etc.) due to severe hypotension, Do not use if patient develops orthostatic hypotension with test dose

Couseling: Don’t stop abruptly
* Titrate slowly (weekly) due to side effects
* Patch: QD, do not use application site for 14 days, remove before MRI

Question 21

What are you COMT inhibitors?

Answer 21

Entacapone (Comtan)
Tolcapone (Tasmar)

Question 22

COMT Inhibitors

Indication, ADR, Counseling

Answer 22

Indication: Preserve levodopa (adjuct only, may need to reduce Sinemet)
ADR: dyskinesias, discolor urine, delayed onset diarrhea (entacapone), hepatotoxicity (tolcapone)
Counseling Do NOT stop abruptly

Question 23

Types of Selective MAO-B Inhibitors?

Answer 23

Selegiline (Eldepryl, Zelapar)

Rasagiline (Azilect)

Safinamide (Xadago)

Question 24

Selective MAO-B Inhibitors | Indications, ADR, CI

Answer 24

**Indication:** Block the breakdown of dopamine, mild motor sx **ADR:** Gi, psych, HA, DZ, HTN, Drowsiness, Insomnia (selegiline) **CI:** Do NOT use with other MAOIs * Tyramine interaction potential -> hypertensive crisis (loss of selectivity at higher doses) * Serotonin syndrome potential: Avoid other serotonergic drugs

Question 25

What are the anticholinerigcs for PD?

Answer 25

Benztropine (Cogentin) Trihexyphenidyl (Artane)

Question 26

Anticholinergics | Indications, ADR, CI, Counseling

Answer 26

**Indication:** Tremors, improve dystonia, taper to avoid rebound PD sx **ADR:** dry mouth, constipation, urinary retention, blurred vision, somnolence, confusion/CNS changes **CI:** elderly, BPH, closed angle glaucoma, dementia, tardive dyskinesia, amantadne may cause additive effects **Counseling:** Taper to avoid rebound PD symptoms

Question 27

Amantadine | Brand, Indication, Caution, ADR

Answer 27

Symmetrel **Indication:** treating Sinemet-induced EPS (dyskinesias) **Caution:** elderly and hx of seizures **ADR:** Anticholinergic effects, Reversible skin reaction (Livedo reticularis – reddish purple mottling of the skin)

Question 28

Types of Adenosine A2A Antagonists?

Answer 28

Istradefylline (Nourianz)

Question 29

Adenosine A2A Antagonists ## Footnote Indication, ADR, Caution,

Answer 29

**Indication:** adjunct treatment with Sinemet to reduce “off” episodes **ADR:** GI, hallucinations, psychosis, insomnia, dyskinesias **Caution:** dose adjustment for smokers and CYP3A4 inhibitors * dyskinesias or psychotic disorders

Question 30

What are the drugs that induce PD?

Answer 30

**Metoclopramide:** Used to treat gastroparesis, nausea/vomiting **Antipsychotics:** First generation – most likely to cause EPS (Haloperidol, prochlorperazine) * Some second generation – risperidone, paliperidone * Quetiapine, clozapine – least likely

Question 31

What are frequent comorbidities of PD? Drugs that induce them?

Answer 31

1. Depression (Choose treatment based on side effects and drug interactions) 2. Psychosis (Pimavanserin, quetiapine, clozapine) 3. Dementia (Rivastigmine)

Question 32

What is an essential tremor?

Answer 32

A neurological disorder characterized by rhythmic, involuntary shaking mainly in the upper extremities * bilateral and symmetric

Question 33

What are the sx associated with ET?

Answer 33

1. head, voice, tongue, face/jaw, or lower limbs movement 2. worsened by stress, fatigue, caffeine, or extreme temperatures 3. Can interfere with daily tasks 4.>70 YO

Question 34

Compare PD vs ET?

Answer 34

Question 35

How is ET diagnosed?

Answer 35

1. Bilateral postural and/or kinetic tremor, involving the hands and arms, that is visible and persistent 2. Duration >5 years 3. Rule out other causes 4. ET does NOT respond to levodopa treatment.

Question 36

What are the tx for ET?

Answer 36

**Beta blockers:** Propranolol, atenolol, nadolol **Anticonvulsants:** Primidone, gabapentin, topiramate, pregabalin **Benzodiazepines:** Alprazolam, clonazepam **Botulinum Toxin Type A (Botox)** **Surgery**

Question 37

What is the first line for ET?

Answer 37

1. Propranolol 2. Primidone

Question 38

What is RLS?

Answer 38

Paresthesia felt deep in the calf muscle (or arms/thighs) resulting in the urge to keep limps in motion

Question 39

What are the RF of RLS?

Answer 39

1. CKD 2. Iron def 3. Pregnancy 4. Caffeine 5. Stress 6. Alcohol 7. Fatigue

Question 41

How do you diagnose RLS?

Answer 41

1. Urge to move limbs usually associated with discomfort 1. Symptoms begin/worsen during rest or inactivity 1. Symptoms exclusively present or worse in the evening or at night 1. Symptoms are temporarily relieved by movement 1. Symptoms are not accounted for by other medical conditions 1. Discomfort returns when the person tries to sleep -> insomnia

Question 42

What are the tx for RLS?

Answer 42

**DA:** monitor for compulsive behaviors **Sinemet:** monitor for more symptoms **Gabapentin/Pregabalin:** monitor for dizziness/falls **Opiods:** monitor for tolerance, RLS symptoms and response to therapy **Sedative hypnotics:** monitor for sedation **Iron:** if def, but montior for constipation