Drug Therapy - Parkinson's & MS Flashcards
Which hormone/neurotransmitter is depleted in Parkinson’s Disease?
Dopamine
Diagnosis of Parkinson’s Disease
- Bradykinesia + 2 or more of the following:
- limb muscle rigidity
- resting tremor (attenuated by movement)
- postural instability
- micrographia
- Lack of other neurologic impairment
- Responsiveness to L-dopa
- Rule out drug-induced
What are the treatment goals of Parkinson’s Disease?
- Maintain patient independence, ADLs, and QOL
- Alleviate symptoms
- Minimize development of response fluctuations
- Limit medication-related adverse effects
Name the three classes of drugs used in pharmacologic therapy of PD.
- Dopamine Enhancers
- Dopamine Agoninsts
- Anticholinergics
Name the four sub-classes of Dopamine Enhancers.
- Levodopa/Carbidopa
- Amantadine
- MAO-B Inhibitors
- Selegiline & Rasagiline
- Catechol-o-methyltransferase (COMT) inhibitors
- Entacapone & Tolcapone
What is the most effective treatment of PD?
Levodopa/Carbidopa
What is the MOA for Levodopa/Carbidopa?
- Increases dopamine (DA) in the CNS
- Levadopa is the immediate precursor to DA, crosses the BBB (DA does not)
- Carbidopa inhibits peripheral conversion of levodopa to DA
Why do you titrate Levodopa/Carbidopa doses slowly?
To avoid peripheral adverse effects - nausea, vomiting, hypotension
What is the MOA for Amantadine?
NMDA receptor antagonist, blocks glutatmate transmission, promotes DA release, and blocks Ach
What is the concern with abrupt discontinuation of Amantadine?
Rebound Parkinson’s Disease
Name the MAO-B Inhibitors
- Selegiline
- Rassagiline
What is the MOA for MAO-B inhibitors?
- Prevent breakdown of DA via MAO-B
Which PD medication may be neuroprotective and neurorestorative?
Rasagiline
Why do you avoid MOA-B use with TCA, SSRI, SNRI, and meperidine?
- CNS toxicity
- autonomic instability
- HTN
- increased temp
- death
What is the MOA of COMT inhibitors?
Inhibit breakdown of levodopa
Name the COMT inhibitors
- Entacapone
- Tolcapone
What doe COMT inhibitors do to levodopa?
Increase the half life by 50% –> more continuous stimulation of dopamine receptors
What is the trade name of Levodopa/Carbidopa?
Sinemet
What is the trade name for Rasagiline?
Azilect
What is the trade name for Entacapone?
Comtan
What are the adverse effects of dopamine enhancers?
- agitation
- confusion
- insomnia
- psychosis
- headache
- dizziness
- orthostasis
- dyskinesias
- nausea
- vomiting
What is the benefit to dopamine agonists?
- May delay need for use of levodopa in early disease or decrease the dose of levodopa in advanced disease
What is the trade name of Pramipexole?
Mirapex
What are the adverse effects of dopamine agonists?
- confusion, dizziness, hallucinations, orthostasis, nausea, asthenia, syncope, peripheral edema
What happens when there is excess dopamine?
- CNS Effects
- confusion, hallucinations
- Systemic Effects
- GI complains, orthostatic hypotension
What is the MOA of anticholinergics in PD?
decreased cholinergic activity leads to improvement in tremor
What is often used as adjuvant therapy in early PD?
Anticholinergics - Benztropine (Cogentin)
What are the adverse effects of anticholinergics?
- confusion
- memory loss
- anti-SLUD
- sedation
- depression
- orthostasis
- drowsiness
What is the trade name of Benztropine?
Cogentin
What are some common motor complications of PD treatment?
- End-of-dose “wearing off”
- “Delayed on” or “no on” response
- Start hesitation (freezing)
- Peak-dose dyskinesia
What are possible treatments for end-of-dose wearing off?
- Decrease levodopa dosing interval by 30-60 min
- Add COMT inhibitor if on levodopa (may require levodopa dose decrease)
- Add dopamine agonist to levodopa or vice versa
- Add MAO-B inhibitor to levodopa
What are possible treatments for “delayed on” or “no on” response?
- Give levodopa on empty stomach
- Use levodopa ODT
- Avoid levodopa CR
- Use apomorphine subcutaneous
What are possible treatments for start hesitation or “freezing”
- Increase levodopa dose
- Add a dopamine agonist or MOA-B inhibitor
- Utilize physical therapy along with assistive walking devices or sensory cues (e.g rhythmic commands, stepping over objects)
What are some possible treatments to Peak-dose dyskinesia?
- decrease levodopa dose and add/increase DA agonist
- Add amantadine
- If COMT inhibitor recently added, consider levodopa decrease
Which PD medication can be used to treat hypomobility?
Apomorphine (Apokyn)
What can be used to treat PD associated hallucinations and psychosis?
- Quetiapine (Seroquel) is recommended
- Clozapine can also be considered but requires frequent lab monitoring
What can be used to treat PD associated dementia?
- donepezil or rivastigmine
Which MS Classification is most common?
Relapsing Remitting
What are the treatment goals of MS?
- Decrease severity, intensity, and duration of exacerbations
- Enhance exacerbation recovery
- Prevent relapse and onset of progressive disease
- Stop or reverse progressive MS
- Provide spymptomatic relief from MS complications
What is the MOA of corticosteroids in MS?
- Unclear
- May help preseve myelin and maintain BBB integrity
Name the corticosteroids used in MS
- Methylprednisolone
- Prednisone
What is the dose of Methylprednisolone in MS?
500-1000 mg/day IV x 3-5 days (rarely up to 10 days)
What is the dose of Prednisone in MS?
PO 1250mg qoday x 5 doses
When do you use corticosteroids in MS?
Reserved for exacerbations with functional consequence
What are corticosteroid adverse effects?
- GI upset
- insomnia
- mood swings
When do you treat MS with plasma exchange?
- Used for patients with very severe attacks (hemiplegia, paraplegia, quadriplegia) that do not respond to aggressive corticosteroid treatment
Name the Disease Modifying Therapies for MS
- Interferons
- Glatiramier (Copaxone)
- Fingolimod (Gilenya)
- Teriflunomide (Aubagio)
- Dimethyl fumarate (Tecfidera)
- Mitoxantrone (Novantrone)
- Natalizumab (Tysabri)
What are the trade names for Interferon B-1a?
- Avonex
- Rebif
What are the trade names for Interferone B-1b?
- Betaseron
- Extavia
What is the MOA of Interferons in MS?
- alter the expression and response to surface antigens, can augment cell function, suppress T-cell proliferation, may decrease BBB permeability
Why are Interferons used in MS?
Decrease frequency of exacerbations and delay disability
Considered 1st line treatment
What do you need to monitor for Interferon therapy?
- EDSS (expanded disability status scale)
- Baseline CBC, plt
- LFTs @ 1 month, then q3 months x 1 year, then q6 months thereafter
What is the MOA of Glatiramer in MS?
may suppress T-lymphocytes specific for myelin antigen
What type of MS is Glatiramer indicated for?
Relapsing Remitting
What is the efficacy of Glatiramer?
- Decreases relapses by 28% each year compared to placebo; also postpones relapses
- First line DMT based on tolerability and efficacy
What are the adverse effects of Glatiramer?
- vasodilation
- arthralgia
- chest pain
- injection site reaction
What is the dose of Glatiramer?
20 mg SQ qd
40 mg 3x/week
What is the MOA for Fingolimod in MS?
prevents some WBCs from migrating to CNS and subsequent damage
What type(s) of MS is Fingolimod indicated for?
- Relapsing remitting
- Progressive relapsing
What is the efficacy of Fingolimod?
- modestly better than Avonex at preventing relapses
What are the adverse effects of Fingolimod?
- HA
- increased LFTs
- decreased HR
- heart block (1st dose monitoring with EKG)
- macular edema
- bronchitis
- pneumonia
- Avoid in patients with recent MI, angina, stroke, TIA, or severe HF
What is the MOA of Teriflunomide in MS?
- may involve a reduction in the number of activated lymphocytes in the CNS
Which types of MS is Teriflunomide indicated for?
- The relapsing forms (RR, PR)
What are the adverse effects of Teriflunomide?
- nausea
- diarrhea
- hair loss
- hepatotoxicity (black box warning)
- increased infection risk
- Teratogenic: reliable contraception is needed for women of child bearing potential
What needs to be monitored when patients are taking Teriflunomide?
- LFTs - baseline, qmonth x 6 months, then periodically
Which DMT is often used in conjunction with Interferons?
Mitoxantrone (Novantrone)
What is Natalizumab indicated for?
- monotherapy for relapsing forms of MS to delay physical disability and decrease relapses in patients who have documented inadequent responses or intolerance to traditional MS therapies
What are the adverse effects of Natalizumab?
- rare PML (progressive multifocal leukoencephalopathy)
Which MS medication may increase walking speed?
Dalfampridine (Ampyra)
