Conditions Effecting the Nervous System and PharmacotherapyPart Five: Neurodegenerative DX- Multiple Sclerosis MS Flashcards
Exam 4 (Final)
Multiple Sclerosis: What is it?
Chronic inflammatory autoimmune disorder damages myelin sheath of CNS neurons
Multiple Sclerosis:
What happens in MS?
Immune system (lymphocytes & macrophages) attack myelin sheath (insulation) surrounding nerve fibers
Multiple Sclerosis:
What gets interrupted?
Electrical impulse conduction gets interrupted
Multiple Sclerosis:
What may stimulate an abnormal immune response?
Viruses may stimulate abnormal immune response
Multiple Sclerosis
What does it result in?
Results in inflammation, loss of myelin, scarring producing plaques (sclerosis)
Multiple Sclerosis
What are there periods of?
Initial periods of exacerbation (relapses/flares) & alternating periods of partial/complete recovery (remission) but sometimes unrelenting
Multiple Sclerosis
What happens to symptoms overtime?
Over time sx –> progressive worse – NO CURE!
Multiple Sclerosis:
How is the disease pattern?
Unpredictable disease pattern
Multiple Sclerosis:
What is the etiology?
Etiology unknown
Multiple Sclerosis:
When is onset? Who is it more common in?
Onset between 20-40 yrs of age, more common in women, but men have more progressive course
Multiple Sclerosis:
Where is there a higher prevalence?
Prevalence higher in northern latitudes
Multiple Sclerosis:
What are inconclusive risk factors?
Inconclusive risk factors:
smoking,
vitamin D deficiency,
obesity,
infection,
genetics,
autoimmune reactions,
environmental toxins
Patho of MS
What is the hallmark?
Hallmark is multifocal regions of inflammation & myelin destruction in brain, spinal cord, optic nerve.
Patho of MS:
What is mistaken by immune system?
Immune system mistakes myelin components of the CNS (not PNS) as foreign & attacks!!!
Patho of MS:
What is Oligodendrocytes?
Oligodendrocytes produce myelin, which insulates the axons and allows nerve signals to be transmitted.
Patho of MS:
What triggers release of inflammatory mediators & oligodendrocyte loss?
Autoreactive T & B cells, & macrophages cross BBB, attack myelin, trigger release of inflammatory mediators & oligodendrocyte loss
Patho of MS
What contributes to inflammation and injury?
Resident brain macrophages (glial cells) get activated, contribute to inflammation & injury
Patho of MS
What happens to myelin and oligodendrocytes?
Myelin destroyed and oligodendrocytes injured and die.
Patho of MS cont.
What occurs throughout the whole central nervous system?
Demyelination throughout the central nervous system.
Patho of MS cont.
What happens to destroyed myelin?
The destroyed myelin is replaced by hard lesions from the damage
Patho of MS cont.
What can inflammation do?
Inflammation can damage axons & oligodendrocytes
Patho of MS cont.
What happens as more myelin is destroyed?
As more myelin is destroyed, nerve conduction is slowed, resulting in weakness, coordination difficulties, visual impairment, and speech disturbances.
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: What do attacks lead to?
Attacks lead to damage to the myelin sheaths in the brain and spinal cord.
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: What is not yet impacted?
Nerve fiber is not yet impacted.
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: What is not yet impacted?
Nerve impulses continue to be transmitted but are slowed.
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: How is patient?
Patients become aware of impaired function (weakness).
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: How is the myelin?
Myelin is capable of regenerating, and as it regenerates, the symptoms disappear.
Progression of Multiple Sclerosis
Damage to Myelin
In the initial stages: What do patients experience?
Patients experience remission.
Progression of Multiple Sclerosis
Damage to Myelin
What may eventually form due to myelin loss?
Eventually plaque development from myelin loss:
Progression of Multiple Sclerosis
Damage to Myelin
Eventually plaque development from myelin loss:
How are initial plaques?
Initial plaques are pink and swollen.
Progression of Multiple Sclerosis
Damage to Myelin
Eventually plaque development from myelin loss:
How do they become progressively?
They progressively become gray and firm.
Progression of Multiple Sclerosis
Damage to Myelin
Eventually plaque development from myelin loss:
What size are the plaques? How may they become?
They vary in size.
They may merge into a single patch.
When acute attack is over:
Inflammation subsides
Some degree of recovery at least in the early stages
Recurrent episodes ~ less and less complete recovery/remyelination
When acute attack is over:
Inflammation subsides: What happens to damaged tissue?
Damaged tissue replaced.
Astrocytes contribute to the repair & scarring process
When acute attack is over:
Inflammation subsides: What forms?
Formation of scars ~ scleroses
When acute attack is over:
Some degree of recovery at least in the early stages due to:
Partial remyelination
Axonal compensation ~ redistribution of Na channels
When acute attack is over:
Some degree of recovery at least in the early stages:
Due to what developing?
Development of alternative neuronal circuits, bypassing damage
When acute attack is over:
Recurrent episodes ~ less and less complete recovery/remyelination
What develops? What happens to neurons and oligodendrocytes?
Mounting astrocytic scarring
Irreversible axonal injury
Death of neurons and oligodendrocytes
Progression of Multiple Sclerosis:
What occurs?
Loss of Axon Function
Progression of Multiple Sclerosis:
Loss of Axon Function: With disease progression
What continues?
Inflammation continues.
Progression of Multiple Sclerosis:
Loss of Axon Function: With disease progression
What happens to myelin?
Myelin loses its regeneration capability.
Progression of Multiple Sclerosis:
Loss of Axon Function: With disease progression
What gets impacted by the inflammation occurring?
Adjacent oligodendrocytes are impacted.
Progression of Multiple Sclerosis:
Loss of Axon Function: With disease progression
How is axon impacted?
Damage occurs to the axon.
Progression of Multiple Sclerosis:
Loss of Axon Function: With disease progression
What happens to nerve transmission? What does this lead to?
Nerve transmission is disrupted in all types of nerve fibers (motor, sensory, autonomic) leading to permanent loss of nerve function.
Progression of Multiple Sclerosis
Loss of Axon Function:
What each relapse involve?
Each relapse involves additional areas of the CNS.
Progression of Multiple Sclerosis
As the inflammatory process diminishes:
What happens to damaged tissue?
Damaged tissue is replaced with glial scar tissue.
Progression of Multiple Sclerosis
Loss of Axon Function:
How does severity of the disease occur?
Severity of the disease progression varies from a slow progression in some patients and a rapid progression in others.
Progression of Multiple Sclerosis
As the inflammatory process diminishes:
What is created?
It results in the creation of hard, sclerotic plaques.
Progression of Multiple Sclerosis
As the inflammatory process diminishes:
It results in the creation of hard, sclerotic plaques. Where is this found?
It is found in the CNS white matter.
Clinical Manifestations
Damage to cerebellum
Emotional & behavioral changes
Damage to cranial nerves
Damage to motor nerve tracts
Damage to sensory nerve tracts
Clinical Manifestations:
Damage to cerebellum causes what?
Loss of balance
Ataxia
Clinical Manifestations:
Damage to cranial nerves causes what?
Visual disturbances
Diplopia (double vision)
Loss of vision
Scotoma (spot in the visual field)
Disturbances with verbalization
Dysarthria (poor articulation)
Clinical Manifestations:
Damage to motor nerve tracts causes what?
Weakness
Paralysis
Spasticity
Urinary incontinence
Clinical Manifestations:
Damage to sensory nerve tracts causes what?
Paresthesia of face, trunk, limbs
MS subtypes:
What are they?
Clinical Isolated Syndrome
Relapsing-Remitting (RRMS)
Secondary-Progressive (SPMS)
Primary-Progressive (PPMS)
MS subtypes:
What is the worst subtype?
Primary-Progressive (PPMS)
The worst
MS subtypes:
Clinical Isolated Syndrome: What are neuro symptoms caused by?
What is this subtype considered?
Neuro symptoms caused by demyelination & inflammation last for at least 24 hours
1st episode of MS
MS subtypes:
What is the most common category of MS experienced? What percent of patients are in this category?
Relapsing-Remitting (RRMS)
Most common category of MS experienced (85% of diagnosed patients are in this category).
MS subtypes:
Relapsing-Remitting (RRMS):
What is it characterized by?
Defined periods of deteriorating neurologic function (relapses).
Followed by partial or complete recovery (remission).
MS subtypes:
Relapsing-Remitting (RRMS):
How do symptoms develop? How do symptoms vary?
Sx develop over several days, resolve within weeks
S/sx vary based on size/location of lesion
MS subtypes:
Relapsing-Remitting (RRMS):
On average, how many relapses?
Avg: 2 relapses every 3 years
MS subtypes:
Secondary-Progressive (SPMS): What characterizes the initial course?
Relapses and remissions characterize initial course.
MS subtypes:
Secondary-Progressive (SPMS):
What is this?
When a pt with RRMS develops steadily worsening dysfunction & followed by chronic progression.
MS subtypes:
Secondary-Progressive (SPMS):
How do Remission/relapse/plateau occur?
Remission/relapse/plateau may occur infrequently.
MS subtypes:
Secondary-Progressive (SPMS):
What do new treatments do for this?
New treatments may slow down progression.
MS subtypes:
Secondary-Progressive (SPMS):
What eventually progresses in this category?
Most relapsing-remitting eventually progress to this category.
MS subtypes:
Secondary-Progressive (SPMS):
How many people will develop this subtype?
Within 10 to 20 years of onset, about 50% of patients with MS will develop this type
MS subtypes:
Primary-Progressive (PPMS)
The worst
How many MS patients is this seen in ?
It is seen in 10% of MS patients.
MS subtypes:
Primary-Progressive (PPMS)
The worst
What occurs in this?
There is a steady deterioration of neurologic function from outset.
Minor improvements/ plateaus may occur.
MS subtypes:
Primary-Progressive (PPMS)
The worst
What does not occur in this?
No distinct remission or relapse occurs.
Diagnosis of MS
How is diagnosis ? What is the definite test?
Delayed DX
⍉ definitive test
Diagnosis of MS
What can symptoms occur with or without?
Sx can occur with or without lesions
Diagnosis of MS
Diagnostics
PMH
PE
MRI – most sensitive test
Lumbar puncture with CSF analysis
Nerve conduction studies
Diagnosis of MS
MRI – most sensitive test
When do the first lesions begin?
The first lesions begin in conjunction with the inflammatory response.
Diagnosis of MS
MRI – most sensitive test
What is seen in the MRI?
large areas of inflammation and demyelination plaques typically seen next to the lateral ventricles, brain stem, and optic nerve.
Diagnosis of MS
Lumbar puncture with CSF analysis
What is measured?
Levels of protein, gamma globulin, lymphocytes
Diagnosis of MS
Nerve conduction studies
What does it measure?
Decreased conduction velocity in visual, auditory, sensory pathways
Management Overview for MS:
What is the purpose of management?
Slow progression, prevent exacerbations, tx relapse & permanent damage
Minimizing symptoms & modify disease process, maximizing QOL
Management Overview for MS:
How to treat chronic fatigue?
Chronic fatigue – overwhelming, rest
Management Overview for MS:
How to treat sexual dysfunction ?
Sexual dysfunction – Sildenafil (Viagra)
Management Overview for MS:
How to treat Depression/Cognitive dysfunction?
SSRIS, Donezepril
Referrals – PT/OT/VNS, support groups, local MS chapter, counseling
Management Overview for MS:
How to decrease core body temp?
Use AC, cooling blankets to decrease core body temp
Management Overview for MS:
Mobility issues:
Respiratory infections
Decubitus ulcer formation - Skin care – pressure relief, moisturize
Contractures – PT/OT
Spasticity
Management Overview for MS:
Mobility issues: Spasticity- how treat?
Spasticity – anti-spasmodics, PT for strengthening
Management Overview for MS
Due to development of plaques along the spinal tract
What develops?
Bowel disorders
UTI/Bladder dysfxn:
Sexual dysfunction
Management Overview for MS
Due to development of plaques along the spinal tract
Bowel disorders - How to treat?
bulk-forming lax, stool softeners, fiber, fluids
Management Overview for MS
Due to development of plaques along the spinal tract
UTI/Bladder dysfxn: - How to treat?
OAB, intermittent cath, antibiotics
Management Overview for MS
Due to development of plaques along the spinal tract
Sexual dysfunction - How to treat?
Sexual dysfunction – meds for ED
Management Overview for MS
How to treat pain and other abnormal sensations?
Pain (neuropathic) & other abnormal sensations –
Gabapentin,
muscle relaxants,
NSAIDs,
antiepileptic drugs
Management Overview for MS
Dysphagia- How to treat?
Dysphagia – thick fluids, soft foods, aspiration precautions, PEG tube
Management Overview for MS
TX strategies: What meds?
GC ~ acute episodes (relapses)
Management Overview for MS
TX for Acute Episode (Relapse): What is it?
High-dose IV GC ~ methylprednisolone
Management Overview for MS
TX for Acute Episode (Relapse):
High-dose IV GC ~ methylprednisolone
What is it for? How long is course?
Suppress inflammation
Reduce attack severity
Short course ~ 3-5d
Management Overview for MS
Disease-modifying agents: What are they?
Immunomodulators
Management Overview for MS
Plasmapheresis: What are they?
Unresponsive exacerbations
Management Overview for MS
Gamma globulin (immune globulin): What are they for? What are they reserved for?
Acute episodes
Reserved for TX failure or GC-intolerance or contraindicated
MS Pharmacotherapy AKA
AKA “Disease-modifying drugs”
MS Pharmacotherapy AKA “Disease-modifying drugs”
What do they decrease?
Decrease frequency & severity of relapse
MS Pharmacotherapy AKA “Disease-modifying drugs”
Decrease frequency & severity of relapse how?
↓ development of brain lesions & disability, frequency & severity of relapses, future disability
Slow axon damage
Maintain quality of life
MS Pharmacotherapy AKA “Disease-modifying drugs”
Decrease frequency & severity of relapse:
What does it prevent?
May prevent damage to axons
MS Pharmacotherapy AKA “Disease-modifying drugs”
Decrease frequency & severity of relapse: Is it effective in everyone? Who does it benefit the most?
⍉ efficacy in all patients
Relapsing-remitting benefit most
$$$
MS Pharmacotherapy
2 main groups: What are they?
Immunomodulators, safer & preferred
Immunosuppressants
MS Pharmacotherapy
2 main groups:
Immunomodulators, safer & preferred
What are the names?
Interferon beta 1a & 1b
MS Pharmacotherapy
2 main groups:
Immunomodulators, safer & preferred
Interferon beta 1a & 1b: When do you start this drug? How long does treatment continue?
Begin soon after dx to prevent permanent neuro deficits & axonal injury
Tx continues indefinitely
MS Pharmacotherapy
2 main groups:
Immunosuppressants: When is this used?
If tx with immunomodulator fails
MS Pharmacotherapy
2 main groups:
Immunosuppressants: What is the example drug?
Mitoxantrone
MS Pharmacotherapy
2 main groups:
Immunosuppressants:
Mitoxantrone: What is a serious problem with this drug?
Can cause serious toxicity
Myelosuppression, heart damage
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
What kind of actions do they have?
Antiviral, antiproliferative, and immunomodulatory actions
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
How is natural interferon beta produced?
Natural interferon beta produced in response to viruses
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
What does this inhibit?
Inhibits migration of proinflammatory leukocytes across BBB, preventing these cells from reaching CNS neurons
Interferon Beta (Disease Modifying Drug I: Immunomodulator)
What does it suppress?
Suppresses T-helper cell activity
Interferon Beta (Disease Modifying Drug I: Immunomodulator)
What is it manufactured using?
Different preparations, given by injection, manufactured using recombinant DNA technology
Interferon Beta (Disease Modifying Drug I: Immunomodulator)
What shouldn’t be administered while doing this med?
Live vaccines shouldn’t be administered during therapy to avoid risk of virus transmission
Interferon Beta (Disease Modifying Drug I: Immunomodulator)
Live vaccines shouldn’t be administered during therapy to avoid risk of virus transmission.
When should live vaccines be given if needed?
Give 4-6 wks before therapy
Interferon Beta (Disease Modifying Drug I: Immunomodulator)
What are the therapeutic uses of this drug?
Reduces the frequency and severity of attacks
Reduces the number and size of lesions detectable with MRI
Delays progression of disability
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
How often should this drug be given?
Given once a week, QOD, 3x a week by IM/Sq injection – depends on preparation
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions
Flu-like reactions
Hepatotoxicity
Myelosuppression
Injection-site reactions
Depression
Suicidal thoughts
Neutralizing antibodies
Drug interactions
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Flu-like reactions
How to minimize symptoms? What can also be used for these symptoms?
Minimize sx by starting with low dose, titrating up
Acetaminophen, ibuprofen
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Hepatotoxicity
What should be done to prevent?
Monitor? Baseline, 1 mo, 3 mo x 1 yr, every 6 mos after
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Myelosuppression
What should be done to prevent?
Monitor?
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Injection-site reactions
What occurs in injection site reactions? What should be done?
pain, redness, rash itch
Rotate sites, ice, warm compress
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Depression
What occurs that has to do with depression?
May promote or exacerbate
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Neutralizing antibodies
How does this happen with the meds?
Med can stimulate Abs against itself because its immunogenic/foreign protein
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Adverse effects and drug interactions: Drug interactions
Other drugs that suppress bone marrow, cause liver injury
Interferon Beta (Disease Modifying Drug I: Immunomodulator):
Preparation, dosage, and administration
How is it dispensed? What do you educate patient about?
Dispensed as single-use syringes and vials
Pt ed: How to self-inject, store in fridge
Disease-Modifying Drugs II: Immunosuppressants:
Mitoxantrone
How should this drug be handled?
Hazardous agent requiring special handling
Disease-Modifying Drugs II: Immunosuppressants:
What is the prototype?
Mitoxantrone
Disease-Modifying Drugs II: Immunosuppressants
How do they compare to immunomodulators?
More toxic than immunomodulators
Produce greater suppression of immune function
Disease-Modifying Drugs II: Immunosuppressants
What were they originally developed for?
Developed to treat cancer & later approved for MS
Disease-Modifying Drugs II: Immunosuppressants
What is there a significant risk for?
Significant risk for toxicity
Disease-Modifying Drugs II: Immunosuppressants
What is the therapeutic use?
Decreases neurologic disability and clinical relapses in pts with MS (RRMS & SPMS)
May delay the time to relapse, time to disability progression & new MRI-detectable lesions
Mitoxantrone
Mechanism of action: How are they to all cells?
Cytotoxic to all cells, whether dividing or not
Mitoxantrone
Mechanism of action:
What does it bind with?
Binds with DNA and inhibits DNA & RNA synthesis
Mitoxantrone
Mechanism of action:
What does it suppress? What does this lead to?
Suppresses B&T lymphocyte & macrophage production –> decreased autoimmune destruction of myelin
Reduced cytokines (eg TNF, IL-2) that participate in immune response
Mitoxantrone
Mechanism of action:
What is this drug especially toxic to? Like what tissues?
Especially toxic to tissues with high % of actively dividing cells
Bone marrow, hair follicles, GI mucosa
Mitoxantrone:
How is it administered?
Given by infusion - 12mg/m^2 every 3 months (max dose 140mg/ m^2 due to cardiotoxicity)
ADRs Mitoxantrone include:
Myelosuppression
Cardiotoxicity
Fetal harm
Tissue injury with extravasation
Reversible hair loss, injury to GI mucosa, n/v, amenorrhea, allergy symptoms, and blue-green tint to urine, skin, and sclera
ADRs Mitoxantrone include:
Myelosuppression: What occurs?
Loss of neutrophils 10-14d after dosing (check cbc @ baseline, before tx, 10-14d after)
ADRs Mitoxantrone include:
Myelosuppression:
When should you hold the dose?
Hold if neutrophil count falls below 1500 cells/mm3 (norm 2500-7000)
ADRs Mitoxantrone include:
Myelosuppression:
What should be done to avoid myelosuppression?
Avoid sick contacts, report s/sx of infection, no live virus vaccines
ADRs Mitoxantrone include:
Cardiotoxicity:
How does it appear?
Irreversible injury, LVEF reduced or HF, may present months/years after drug use ceases,
ADRs Mitoxantrone include:
Cardiotoxicity:
What should be done to avoid this?
measure LVEF before 1st dose, every dose, if <50% & - hold or if HF s/sx develop
ADRs Mitoxantrone include:
Cardiotoxicity:
Who is this med NOT given to? What is this med related to?
Not to be given if cardiac impairment
Related to cumulative lifetime dose
ADRs Mitoxantrone include:
Tissue injury with extravasation:
What occurs, what must be done to avoid this?
– severe local injury, dilute with at least 50cc NS
ADRs Mitoxantrone include:
Reversible hair loss, injury to GI mucosa, n/v, amenorrhea, allergy symptoms, and blue-green tint to urine, skin, and sclera
What do patients rarely develop?
Rarely pts develop leukemia
Common Immunomodulator/Suppressant Concerns
What shouldn’t be given with Immunomodulator/Suppressants? But if needed, when should it be given?
Live vaccines should not be administered during tx
If needed, give 4-6 wks prior to tx
Common Immunomodulator/Suppressant Concerns
What shouldn’t be given with Immunomodulator/Suppressants due to additive effect?
Avoid other immunosuppressants because of additive effects
Common Immunomodulator/Suppressant Concerns
Because it requires special handling, who does it present a danger to?
Special handling required for certain immunomodulators
Presents hazards for pregnant nurses
Common Immunomodulator/Suppressant Concerns
How are Immunomodulators recognized by body?
Immunomodulators recognized by body as foreign proteins
Common Immunomodulator/Suppressant Concerns
Immunomodulators recognized by body as foreign proteins
What does this do?
Immunogenic, can stimulate production of Abs against itself, decreasing clinical benefits
Common Immunomodulator/Suppressant Concerns
What other changes can occur?
Hypersensitivity reactions
Hematologic changes
Common Immunomodulator/Suppressant Concerns
Vaccine risks: What response if there to vaccines?
Decreased response to vaccines d/t immunosuppressant effects
Common Immunomodulator/Suppressant Concerns
Why are infections common?
Infections are common due to immunosuppressant effects
Common Immunomodulator/Suppressant Concerns
Infections are common due to immunosuppressant effects- What does this lead to?
Opportunistic- Progressive multifocal leukoencephalopathy (PML)
Common Immunomodulator/Suppressant Concerns
Infections are common due to immunosuppressant effects
Opportunistic
Progressive multifocal leukoencephalopathy (PML)
What is this? What kind of symptoms occur? How many people are effected?
Fatal CNS infection
Unilateral weakness, limb clumsiness, disturbed vision, changes in thinking & memory
80-90% left disabled
