Drugs for MS, ALS, & Alzhiemer's

WVSOM Neuro: Schriefer 3/15/11

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Drugs for MS, ALS, & Alzhiemer's by Mind Map: Drugs for MS, ALS, & Alzhiemer's

1. MS

1.1. Interferons

1.1.1. Interferone beta-1b Betaseron Extavia

1.1.2. Interferon beta-1a Avonex Rebif

1.1.3. MOA Immunomodulatory actions Decreases Ag presentation in the CNS Limits immune attack on myelin

1.1.4. PK Major difference btwn the two interferon types is kinetic All are proteins, so much be given via injection B & R are given alternate days SQ injection Avonex is weekly IM injection

1.1.5. SE Flu-like Sx Ab formation (can limit drug effectiveness Depression

1.2. Glatiramer

1.2.1. MOA Synthetic compound that resembles a component of myelin Protects myelin by acting as a "decoy," attracting immune cells away from myelin

1.2.2. Use Relapsing-remitting MS Decreases rate of relapse

1.2.3. Admin Given SQ, QID

1.2.4. SE Generally well tolerated Flushing, chest tightness, SOB Feels like an MI, but it's not! Joint and muscle pain/stiffness

1.3. Mitoxantrone

1.3.1. MOA chemotherapeutic agent suppresses immune attack on myelin

1.3.2. SE N, bladder infxn, mouth sores, amenorrhea Cumulative effect on cardiac conduction Only use for 2-3 years

1.4. Natalizumab

1.4.1. MOA Recombinant MAB Binds adhesion molecule on activated lympho- and monocytes Blocks adhesion and prevents leukocyte entry into CNS

1.4.2. SE Minor Headache, fatigue Allergic rxns and Ab formation The Big Bad one: progressive multifocal leukoencephalopathy (PML) Caused by JC virus

1.5. Fingolimod

1.5.1. MOA Inhibits migration of T cells out of lymph nodes

1.5.2. Use Prevents relapse and progression of Sx

1.5.3. PK Slow but complete absorption Long 1/2 life (4-9 days) Highly protein bound 1st oral specific Tx

1.5.4. SE Bradycardia Increased infxns

2. Symptomatic Tx of MS

2.1. Anti-inflammatory steroids

2.1.1. Methylprednisolone, dexamethasone, prednisone, betamethasone, prednisolone

2.1.2. MOA Close damaged BBB Reduce inflammation in the CNS

2.2. Anti-depressants

2.2.1. Both SSRIs and tricyclics

2.2.2. Use Depression associated w/ MS

2.3. Amitriptyline, Carbamazepine, & phenytoin

2.3.1. Tx for neuralgia

2.4. Imipramine

2.4.1. Use Urinary incontinence

2.4.2. MOA Strong antimuscarinic effect

2.5. Anti-spasmodics (diazepam, clonazepam, dantrolene, etc)

2.6. Amantadine - tremors/fatigue

2.7. Meclizine - vertigo

2.8. Oxybutanin - urinary incontinence

3. Amyotrophic Lateral Sclerosis (ALS)

3.1. Riluzole

3.1.1. The only drug apprvoed for specific Tx of ALS

3.1.2. MOA Voltage-gated Na-channel blocker Inhibits glutamate release Slows progression of Dz

3.1.3. PK Highly plasma bound

3.1.4. SE asthenia, dizziness, vertigo, NVD Circumoral perathesias SGPT elevation Monitor liver chemistry! Tx-limiting

3.2. Non-specific Tx

3.2.1. Baclofen: Tx spacicity

3.2.2. Gabapentin: slows decline in M strength

4. Alzheimer's Dz

4.1. Specific Tx

4.1.1. Acetylcholinesterase inhibitors Donepezil Galantamine Tacrine Revistigmine MOA Pts w/ AD have decreased cholinergic activity in cortex and hippocampus But doesn't really work

4.1.2. Memantine MOA "use-dependent" NMDA receptor antagonist Use Slows progression of Dz Often used as adjunct to cholinesterase inhibitors May be used in other neurodegenerative Dzes (ALS, PD, epilepsy) AE Generally well tolerated Dizziness, headache, constipation, confusion

4.2. Non-specific Tx

4.2.1. SSRIs & atypical antipsychotics Typical antipsychotics increases risk of stroke!

4.2.2. Gingko Modest improvement in memory

4.2.3. Caprylidene MOA AD may be d/t impaired glucose metab. So we're giving them ketones instead Experimental Tx PK "medical food" that is metabolized to ketones. Provide energy to brain