CNS Disorders 1: PD and MS Flashcards
What is the primary pathological mechanism associated with PD?
*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.
What are the clinical symptoms of PD?
*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)
What disorder is associated with loss of ACH and glutamate?
Alzheimer’s disease
What disorder is associated with a loss of GABA?
Huntingtons
What disorder is associated with an imbalance of norepinephrine?
mood disorders like mania or depression
what disorders are associated with an imbalance of serotonin?
depression, suicide, aggression
Describe combination therapy for PD
*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)
what are side effects of levodopa?
GI irritation, Nausea, Anorexia, Hypotension, Psychotropic effects, Dyskinesias, decreased response to medication therapy > 4-5years
(Delayed administration decreases disease progression)
What is the goal of a drug holiday for PD patients?
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
Describe dopamine agonists MOA and AE
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
Describe Dopamine precursor and related agents MOA and AE
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.
Describe monoamine oxidase (MAO) inhibitors MOA and AE
Selegiline, Rasagiline, Safinamide
*MOA: MAO-b inhibition
*AE: serotonin syndrome
Describe Catechol-O-Methyl-Transferase (COMT) Inhibitors MOA and AE
Entecapone, Tolcapone
*MOA: COMT inhibition
*AE: levodopa toxicity nausea, dyskinesias, and confusion. Most importantly can cause acute liver failure.
Describe Amantadine MOA and AE
*MOA: Potentiate dopamine actions/antagonize
glutamate NMDA receptors
*AE: toxicity like nausea, insomnia, dizziness, lightheadedness, hallucinations
What are key pathological hallmarks of MS
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
What is the most common clinical form of MS?
*Relapsing remitting (RRMS): 55%
*Clearly defined flare-ups & remissions; inflammatory lesions
developing constantly
*Early 20s & 30
What is the second most common clinical form of MS?
Secondary progressive (SPMS): 35%
*Relapse frequency
decreases but disability
increases
*Less remyelination &
more plaques, resulting in steadily progressive disability with less recovery
What are the two least common forms of MS?
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
What drugs are used for the treatment of acute MS relapse?
*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
What are disease modifying therapies for MS?
*Injectable: Avonex, Betaseron, Copaxone
*Oral injection: Gilenya, Tecfidera
*Infused: Novantrone, Ocrevus, Tysabri
What is the FDA approved medication for primary progressive MS
Ocrelizumab
What drug is indicated for improved walking speeds in MS patients?
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
List various drugs used for the symptomatic management of MS associated symptoms
*Fatigue: amantadine, methylphenidate
*Spasticity: baclofen, dantrolene, tizanidine
*Bladder symptoms: oxybutynin, prazosin
*Sensory symptoms: gabapentin, pregabalin
What are the common side effects of MS drugs that PTs should be aware of?
muscle weakness, fatigue, dizziness, or heat sensitivity
- What medication is used for acute MS exacerbations
- what is used for the frequency of relapses?
- Corticosteroids
- disease modifying therapies (DMTs)
