Neuro: Schriefer Multiple Sclerosis, Als, And Alzheimer's

Front 1

What is Multiple Sclerosis (MS)

Back 1

a disease of the central nervous system in which neurons become demylinated resulting in motor, sensory, and other problems.

Front 2

General disease characteristics of MS

Back 2

Multiple areas of CNS are affected leading to multiple deficits (many symptoms)

Sclerosis refers to plaque (scar) formation leading to disability

Chronic: life-long disease

Progressive: usually increases in severity over time

Front 3

What are the different types of MS?

Back 3

Benign

Relapsing-remitting: fluctuating course of exacerbations (attacks) and remissions

Secondary progressive

Primary progressive

Front 4

What is important for nl nerve transmission?

Back 4

myelin

myelin is lost

autoimmune

Front 5

In what age group does MS occur commonly?

Back 5

people in 20s and 30s

Front 6

MS Picture

Back 6

Plaques at many sites – the diagnostic hallmark of multiple sclerosis – are illustrated here in paraventricular regions of the frontal lobe and in the central nervous system. The protective myelin sheath, produced by oliqodendrocytes and schwann cells, is destroyed and plaque forms, in part as a result of abnormal immune system activity. An inflammatory response causes edema and decreased nerve conduction. Astrocytes, lymphocytes, and macrophages may further disrupt demyelinated axons.

Front 7

What cells make Myelin?

Back 7

Schwann cells and oligodendrocytes

Front 8

What are the causes of MS?

Back 8

Cause of MS:

Autoimmune disease – there is a cell mediated autoimmune attack against myelin

Viral agent

Genetic predisposition

Front 9

What are the MOTOR symptoms of MS?

Back 9

Motor (movement) symptoms

Ataxia: trouble moving and loss of coordination, i.e., walking

Loss of balance: increased risk of falling

Paralysis: inability to move

spasticity: muscle cramps or spasms

Tremor: shaking of extremities, especially upper limb

Front 10

What nerves are affected with MS:

central or peripheral?

Back 10

ONLY CENTRAL

Front 11

What are Sensory Symptoms of MS?

Back 11

Sensory symptoms

Visual deficits (blurred, reduced, or double vision): usually first symptom to occur

Loss of sensation in limbs

Parethesias: tingling in extremities

Pain

Vertigo

Front 12

What is most common symptom of MS?

Back 12

Fatigue or weakness: most common symptoms

Front 13

What is the Tx of MS?

Back 13

Specific and Nonspecific
Tx

Specific target pathogenesis of Dz

Nonspecific - attack only symptoms

Front 14

Drug Treatment of MS
Specific treatment of disease process

Back 14

Interferons – Two versions of interferon beta-1b (Betaseron & Extavia) and two versions of interferon beta-1a (Avonex & Rebif)

Front 15

What was the MOA for Interferons?

Back 15

uncertain but beneficial effects may be due to immunomodulatory actions. One thought is that INFs decrease antigen presentation in the CNS, which appears to limit immune attack on myelin

Front 16

What interferons work in MS?

Back 16

Beta 1b
and
Beta 1a

EXAM names

Front 17

What is the the major difference between the two interferons are pharmacokinetic (due to slight structural differences).

Back 17

Betaseron (beta-1b) and Rebif (beta-1a) are given by alternate day sc. injections

Avonex (beta-1a) is given by weekly im. injection.

Front 18

how do the interferons have to be given?

Back 18

By injection they are proteins and can be degraded

Front 19

What are adverse Rxn of Interferons?

Back 19

Adverse reactions:

flu-like symptoms (muscle ache, fever, chills, asthenia)

Injection site reactions

Antibody formation (can limit effectiveness of drug)

Depression

Front 20

What is the Clinical use of Interferons?

Back 20

Used to decrease the frequency and severity of exacerbations in patients with relapsing forms of MS. Uncertain whether they actually slow the progression of the disease

used in chronic forms of MS also

Front 21

Another specific Tx for MS

Back 21

Glatiramer

Front 22

What is Glatiramer

Back 22

a synthetic compound which resembles a component of myelin

Front 23

What is the MOA of Glatiramer?

Back 23

Since drug resembles a component of myelin, it’s thought that it may protect myelin by acting as a “decoy” attracting immune cells away from myelin

Front 24

How must Glatiramer be given?

Back 24

Must be given by sc. Injection, once daily

Front 25

What are adverse rxns of Glatiramer

Back 25

Generally well tolerated. The most common side effects are:

Injection site reactions

Flushing, chest tightness or pain, shortness of breath (within 15 min)

Joint pain

Muscle stiffness

Front 26

What is the clinical use of Glatiramer

Back 26

Approved for the treatment of relapsing-remitting MS. Has been shown to decrease the rate of relapse

Front 27

Next specific tx drug for MS

Back 27

Mitoxantrone

Front 28

What does Mitoxantrone do?

Back 28

a cancer chemotherapeutic agent recently approved to treat advanced MS

Acts by suppressing immune attack on myelin

Front 29

What are side effects of Mitoxantrone

Back 29

Common side effects include nausea, bladder infections, mouth sores, and loss of menstrual cycle.

Patients should only receive the drug for 2-3 years due to a cumulative effect on cardiac conduction*****

Front 30

What is the another specific tx for MS?

Back 30

Natalizumab

Front 31

What is Natalizumab

Back 31

A recombinant humanized MAB

Binds to a specific site on an adhesion molecule on activated lymphocytes and monocytes.

This blocks adhesion and prevents leukocyte entry into CNS, therby decreasing immune attack on myelin.

Front 32

What are adverse effects of Natalizumab?

Back 32

Minor – headache, fatigue etc.

Allergic reactions and antibody formation may limit usefulness

Progressive multifocal leukoencephalopathy****EXAM

Front 33

What is the clinical use of Natalizumab?

Back 33

Monotherapy in pts who don’t respond to other drugs. Due to risk of PML, only available in special centers to registered pts.

Front 34

What is the last Specific MS drug?

Back 34

Fingolimod

Front 35

What is Fingolimod?

Back 35

The first oral specific therapy for MS

Mechanism – inhibits migration of T cells out of lymph nodes via action on sphingosine-1-phosphatase receptor.

Pharmacokinetics – slow but complete absorption; highly bound; halflife 4-9 days.

Adverse effects – bradycardia and increased infections

Use – prevent relapse and progression

Front 36

What are the specific tx?

Back 36

1. Interferons beta-1b and beta-1a
2. Glatiramer
3. Mitoxantrone
4. Natalizumab
5. Fingolimod

Front 37

Non-specific Drug Treatment:

Symptomatic treatment

Back 37

Anti-inflammatory steroids – used for management of acute symptoms because they close damaged blood brain barrier and reduce inflammation in the CNS

Front 38

What are your anti-inflammatory steroids?

Back 38

methylprednisolone,
dexamthasone,
prednisone,
betamethasone,
prednisolone

Front 39

Symptomatic treatment (cont.)
for MS

Back 39

Anti-depressants – both SSRIs (e.g., fluoxetine [Prozac]) and tricyclics (e.g., amitriptyline [Elavil]) are used to treat depression associated with MS.

Amitriptyline (and carbamazepine [Tegretol]) are used to treat neuralgia associated with damaged nerves.

Imipramine used to treat urinary incontinence.

Front 40

Symptomatic treatment (cont.)
for MS

Back 40

Anti-spasmodics – a variety of drugs are used to relieve spasms, cramping, and muscle tightness caused by spasticity in MS, including benzodiazepines such as clonazepam (Klonopin) and dizaepam (Valium), baclofen (Lioresal; central GABAB agonist), tizanidine (Zanaflex; central α2 agonist) and dantrolene (Dantrium).

Front 41

Symptomatic treatment (cont.)
for tremors and fatigue

Back 41

Amantadine

Front 42

Symptomatic treatment (cont.)
for vertigo

Back 42

Meclizine

Front 43

Symptomatic treatment (cont.)
for urinary incontinence

Back 43

Oxybutanin

Front 44

Symptomatic treatment (cont.)
for neuralgia

Back 44

Carbamazepine and phenytoin

Front 45

What is Amyotrophic Lateral Sclerosis (ALS)

Back 45

A progressive degenerative disease of motor neurons. Glutamate “excitotoxicity” may be responsible for the disease

Front 46

Drug treatment of ALS

Riluzole

Back 46

is the first (and, so far, only) drug approved for the specific treatment of ALS

Front 47

What is the MOA of Riluzole?

Back 47

Pharmacology
Riluzole is a voltage-gated sodium channel blocker which is thought to act by inhibiting glutamate release

Front 48

Riluzole
Pharmacokinetics

Back 48

Orally effective

Half-life ~ 12 hours

Highly bound to plasma proteins

Hepatic metabolism (some metabolites active) and renal excretion

Front 49

Riluzole
Adverse reactions

Back 49

Asthenia, dizziness, vertigo

Nausea, diarrhea, vomiting

Circumoral parethesias

SGPT elevation (monitor liver chemistry – may require DC)

Front 50

Riluzole

Therapeutic use

Back 50

Has been shown to increase survival in ALS patients but not increase strength or neurological function

Front 51

Drug treatment of ALS

NON-specific Tx

Back 51

consist of baclofen** for spasticity and gabapentin** to slow decline in muscle strength

Front 52

What is Alzheimer’s Disease

Back 52

A progressive, neurodegenerative disease, occurring later in life. It is the most common type of senile dementia, characterized by cognitive deficits, behavioral disorders, and mood changes

Front 53

What is the Drug treatment Alzheimer’s Disease

Back 53

Acetylcholinesterase inhibitors

Front 54

What are the Acetylcholinesterase inhibitors

Back 54

Donepezil
Galantamine
Tacrine
Rivastigmine

Front 55

Acetylcholinesterase inhibitors
MOA

Back 55

the cognitive deficits of the disease are thought to be related, in part, to degeneration of cholinergic neurons in the cortex and hippocampus resulting in deficient cholinergic neurotransmission.

Acetylcholinesterase inhibitors increase cholinergic activity by decreasing metabolism of Ach. Benefit is modest (< 10% improve) and short-lived.

Front 56

Drug treatment Alzheimer’s Disease

Memantine

Back 56

MOA – memantine is a “use-dependent” NMDA receptor antagonist. The theory behind its action in Alzheimer’s is that it blocks glutaminergic overstimulation of NMDA receptors, which can be toxic to neurons which are important in learning and memory, but allows low levels of receptor activation.

Front 57

Memantine
Adverse effects

Back 57

Dizziness, headache, constipation, and confusion. Is generally well tolerated.

Front 58

Memantine

Therapeutic use

Back 58

Provides modest benefit by appearing to slow progression of the disease. Can be used with cholinesterase inhibitors to improve their effectiveness. May also be useful in the treatment of neurodegeneration associated with ALS, Parkinson’s disease, and epilepsy.

Front 59

Drug treatment of Alzheimer’s Disease
SSRI’s and atypical antipsychotics

Back 59

useful for depression and agitation.

Front 60

Drug treatment of Alzheimer’s Disease
Gingko

Back 60

shown to modestly improve memory in some Alzheimer’s patients.

Front 61

Drug treatment of Alzheimer’s Disease
Estrogen

Back 61

Estrogen may increase risk

not good!

Front 62

Drug treatment of Alzheimer’s Disease
Caprylidene

Back 62

a “medical food” metabolized to ketones to provide energy to brain (may be decreased glucose uptake)