CNS Disorders 1: PD and MS

Question 1

What is the primary pathological mechanism associated with PD?

Answer 1

*Dopamine loss underlies the motor symptoms of PD
*presence of lewy bodies in the substantia nigra
*Reduced activation of dopamine 1 and 3 receptors results in greater inhibition of the thalamus
*Decrease in dopamine concentration in the brain causes a relative overactivity of ACH.

Question 2

What are the clinical symptoms of PD?

Answer 2

*Bradykinesia, rigidity, tremor at rest and postural instability directly related to loss of striatal dopamine
*TRAP= Motor symptoms
*SOAP=NON motor symptoms (Sleep disturbance, Other miscellaneus, Autonomic symptoms like drooling and conspitation, Psychological symptoms)

Question 3

What disorder is associated with loss of ACH and glutamate?

Answer 3

Alzheimer’s disease

Question 4

What disorder is associated with a loss of GABA?

Answer 4

Huntingtons

Question 5

What disorder is associated with an imbalance of norepinephrine?

Answer 5

mood disorders like mania or depression

Question 6

what disorders are associated with an imbalance of serotonin?

Answer 6

depression, suicide, aggression

Question 7

Describe combination therapy for PD

Answer 7

*Dopamine does not cross the BBB but the precursor to dopamine, L-DOPA, does cross the BBB.
*Following absorption in the GI tract, L-DOPA is rapidly converted to dopamine by dopa decarboxylase (before reaching brain)
*Carbidopa is used to inhibit dopa decarboxylase enzyme to prevent premature conversion of L-DOPA in the periphery
*Carbidopa works by preventing levodopa from being broken down before it reaches the brain. This allows for a lower dose of levodopa, which causes less nausea and vomiting (GI irritation)
*L-dopa and carbidopa often contained in the same pill (sinemet)

Question 8

what are side effects of levodopa?

Answer 8

GI irritation, Nausea, Anorexia, Hypotension, Psychotropic effects, Dyskinesias, decreased response to medication therapy > 4-5years
(Delayed administration decreases disease progression)

Question 9

What is the goal of a drug holiday for PD patients?

Answer 9

Allow the body to recover from toxicity or tolerance; Maintain patient mobility as much as possible
Levodopa to be resumed at lower dose with better results

Question 10

Describe dopamine agonists MOA and AE

Answer 10

Pramipexole
*MOA: dopamine D3 agonist
Ropinirole
*MOA: Dopamine D2 agonist
Rotigotone
*MOA: Dopamine D2 agonist
*AE for all: sedation, hallucinations, confusion, nausea, orthostatic hypotension, or dyskinesias

Question 11

Describe Dopamine precursor and related agents MOA and AE

Answer 11

Levodopa (L-dopa)
*MOA: dopamine precursor
Levodopa+Carbidopa
*MOA: dopamine precursor
Carbidopa
*MOA: DDC inhibitor
*AE for all: Can cause toxicity such as upset GI tract, arrythmias, dyskinesias, on and off cycles, and behavioral disturbances.

Question 12

Describe monoamine oxidase (MAO) inhibitors MOA and AE

Answer 12

Selegiline, Rasagiline, Safinamide
*MOA: MAO-b inhibition
*AE: serotonin syndrome

Question 13

Describe Catechol-O-Methyl-Transferase (COMT) Inhibitors MOA and AE

Answer 13

Entecapone, Tolcapone
*MOA: COMT inhibition
*AE: levodopa toxicity nausea, dyskinesias, and confusion. Most importantly can cause acute liver failure.

Question 14

Describe Amantadine MOA and AE

Answer 14

*MOA: Potentiate dopamine actions/antagonize
glutamate NMDA receptors
*AE: toxicity like nausea, insomnia, dizziness, lightheadedness, hallucinations

Question 15

What are key pathological hallmarks of MS

Answer 15

Chronically activated pro- inflammatory T lymphocytes and antibodies produced by B- Cells attack myelin sheath in brain & spinal cord, causing demyelination and axonal damage leading to permanent loss of function

Question 16

What is the most common clinical form of MS?

Answer 16

*Relapsing remitting (RRMS): 55%
*Clearly defined flare-ups & remissions; inflammatory lesions
developing constantly
*Early 20s & 30

Question 17

What is the second most common clinical form of MS?

Answer 17

Secondary progressive (SPMS): 35%
*Relapse frequency
decreases but disability
increases
*Less remyelination &
more plaques, resulting in steadily progressive disability with less recovery

Question 18

What are the two least common forms of MS?

Answer 18

Primary progressive (PPMS): 9%
*At onset, steady worsening
without relapses or remissions
*Variations in rates of
progression; occasional
plateaus or temporary minor improvements
Progressive relapsing (PRMS): 1%
*From onset steadily
worsening disease with
clear acute relapses with or without recovery
*Unlike RRMS, remission periods contain clinically
observable continuing
disease progression

Question 19

What drugs are used for the treatment of acute MS relapse?

Answer 19

*When functional ability is affected, the standard intervention is an IV injection of high-dose corticosteroids such as methylprednisolone or oral Prednisone *Adrenocorticotropic hormone (ACTH) is the only FDA-approved agent for MS exacerbation treatment

Question 20

What are disease modifying therapies for MS?

Answer 20

*Injectable: Avonex, Betaseron, Copaxone
*Oral injection: Gilenya, Tecfidera
*Infused: Novantrone, Ocrevus, Tysabri

Question 21

What is the FDA approved medication for primary progressive MS

Answer 21

Ocrelizumab

Question 22

What drug is indicated for improved walking speeds in MS patients?

Answer 22

Dalfampridine
*MOA: Potassium Channel Blocker, prolongs action potentials, improving conduction in
demyelinated neurons
*AE: Urinary tract infections, insomnia, dizziness,
headache, nausea, asthenia, back pain, and balance disorder
*Seizures are rare but serious adverse effect; therefore, patients with seizure disorders should not receive dalfampridine

Question 23

List various drugs used for the symptomatic management of MS associated symptoms

Answer 23

*Fatigue: amantadine, methylphenidate
*Spasticity: baclofen, dantrolene, tizanidine
*Bladder symptoms: oxybutynin, prazosin
*Sensory symptoms: gabapentin, pregabalin

Question 24

What are the common side effects of MS drugs that PTs should be aware of?

Answer 24

muscle weakness, fatigue, dizziness, or heat sensitivity

Question 25

1. What medication is used for acute MS exacerbations
2. what is used for the frequency of relapses?

Answer 25

1. Corticosteroids
2. disease modifying therapies (DMTs)