Conditions Effecting the Nervous System and PharmacotherapyPart Seven: Neurodegenerative DX- Myasthenia Gravis MG Flashcards
Exam 4 (Final)
Myasthenia Gravis MG:
What is the normal function of cholinesterase?
Normal function of cholinesterase is to break down ACh –> choline & acetic acid
Myasthenia Gravis MG: What is it?
MG is a rare chronic, progressive autoimmune disease
Myasthenia Gravis MG:
What occurs?
Antibodies destroy acetylcholine receptors (AChR) at post-synaptic membrane of neuromuscular junction
Myasthenia Gravis MG:
What occurs:
Antibodies destroy acetylcholine receptors (AChR) at post-synaptic membrane of neuromuscular junction
What does this lead to?
Breakdown in the normal communication between nerves and muscles.
Myasthenia Gravis MG:
What causes MG?
Cause: acquired immunological or genetic abnormality, thymic tumors or changes
Myasthenia Gravis MG:
What are typical complaints?
Typical complaints:
muscle weakness,
ocular motor disturbances,
ptosis (droopy eyelid),
or diplopia are the initial symptoms.
Myasthenia Gravis MG:
How is severity of weakness throughout the day?
Severity of weakness fluctuates during the day, usually being least severe in the morning and worse as the day progresses, especially after prolonged use of affected muscles
Myasthenia Gravis MG:
What does weakness involve?
Weakness can involve oropharyngeal and limb muscles.
Myasthenia Gravis MG:
What is treatment for? Is there a cure?
There is no cure for MG, but treatment can help relieve signs and symptoms
Prevalence and Exacerbating Factors of Myasthenia Gravis:
How common is it? Who is it in more?
Rare
More common in women
Prevalence and Exacerbating Factors of Myasthenia Gravis:
Precipitating Factors for Exacerbations
Emotional stress
Pregnancy or menses
Trauma
Temperature extremes
Hypokalemia
Ingestion of drugs
Psychotropic drugs
Prevalence and Exacerbating Factors of Myasthenia Gravis:
Precipitating Factors for Exacerbations:
Ingestion of what drugs can aggravate MG?
Ingestion of drugs, including aminoglycoside, macrolide, tetracycline & fluoroquinolone antibiotics, β-adrenergic & Ca++ ch blockers, and phenytoin aggravate MG
Patho of MG:
What happens first?
Autoantibodies bind to the receptors at the NMJ, preventing acetylcholine from binding to them
Patho of MG:
What happens after Autoantibodies bind to the receptors at the NMJ, preventing acetylcholine from binding to them?
Eventually autoantibodies attack specific receptors found at the neuromuscular junction
Patho of MG:
Eventually autoantibodies attack specific receptors found at the neuromuscular junction
What does this cause?
Prevents muscle from responding to the nerve signal.
Patho of MG
In MG, - antibodies bind & attack the acetylcholine (nicotinicM) receptors at the neuromuscular junction.
What happens to the number of sites?
Decreased ACh receptor sites at the NMJ
Patho of MG
In MG, when there is a decreased number of acetylcholine receptor sites at the NMJ
What happens to the acetylcholine?
ACh can’t attach to receptors and induce muscle contraction
Patho of MG
When ACh can’t attach to receptors and induce muscle contraction –>? What happens?
skeletal muscle weakness, and fatigue of the affected muscles.
Patho of MG
When ACh can’t attach to receptors and induce muscle contraction –> skeletal muscle weakness, and fatigue of the affected muscles
What muscles are usually affected initially?
The facial and ocular muscles are usually affected initially, followed by the arm and trunk muscles.
Patho of MG:
What is acetylcholine responsible for normally?
Ach is responsible for movement.
Patho of MG:
Normally, how is normal voluntary movement possible?
ACh moves across the neuromuscular junction to the nicotinicM receptors & makes voluntary movement possible.
Patho cont’d:
90% of patients with generalized MG have what?
90% of patients with generalized MG have anti-acetylcholine receptor antibodies detectable in their blood.
Patho cont’d:
What other disorders are common in patients with MG? What does this suggest?
Disorders of the thymus such as hyperplasia and tumors are common in patients with MG, suggesting autoantibody production occurs in the thymus.
Clinical Presentation & DX of MG:
How do AchR receptor sites and autoantibody attacks occur?
AchR receptor sites and Ab attack varies
Clinical Presentation & DX of MG:
How is onset?
Insidious onset
Clinical Presentation & DX of MG:
What is first effected?
Face, throat & neck muscles 1st affected
Clinical Presentation & DX of MG:
Face, throat & neck muscles 1st affected
What are the effects?
Facial drooping
Throat muscles, esophagus: dysphagia
Vision issues:
Drooling, diff chewing & swallowing
Clinical Presentation & DX of MG:
Face, throat & neck muscles 1st affected
What are the visual issues effects?
diplopia, ptosis, blurred vision, difficulty moving eyes
Clinical Presentation & DX of MG:
What are other effects?
Muscle fatigue after exercise
Progressive weakness
Dyspnea, impaired ventilation (severe MG)
Clinical Presentation & DX of MG:
When may symptoms first appear?
Sx may 1st appear in pregnancy, PP, or with anesthesia
Clinical Presentation & DX of MG
Diagnostics
PE & neuro assessment
Serum antibody levels
Nerve conduction study
Electromyographic (EMG) studies
Thymus CT, MRI
Edrophonium
Autoimmune testing
Clinical Presentation & DX of MG
Diagnostics: What is included in autoimmune testing?
ESR
ACh receptor antibodies
Antinuclear antibody
Myasthenic Crisis: What is it?
Acute exacerbation
Myasthenic Crisis: What is it characterized by?
Characterized by an increase in weakness and fatigue, and respiratory impairment may develop requiring ventilator support to maintain oxygenation.
Myasthenic Crisis: How does it develop?
Develops as disease progresses
Myasthenic Crisis: What happens to muscles?
Muscles too weak to maintain ventilation
Myasthenic Crisis:
There is Muscles too weak to maintain ventilation
Paralysis –> death
Quadriparesis, quadriplegia –> resp arrest
Myasthenic Crisis:
Muscles too weak to maintain ventilation- why does this occur?
Caused by inadequate medication
Myasthenic Crisis
Exacerbating factors
Fatigue, illness, stress, pregnancy
Extreme heat, emotional distress, infections
EtOH consumption/med exposure/inadequate medication
Myasthenic Crisis
How is it treated?
TX with cholinesterase inhibitor
Myasthenic Crisis
TX with cholinesterase inhibitor includes what?
Neostigmine (Bloxiverz, Prostigmin),
Pyridostigmine (Mestinon)
Management of MG:
Before patient takes PO meds, what must be assessed? How?
Assess swallow ability for PO
Sips of H2O
Management of MG:
Medications
Cholinesterase inhibitors
Immunosuppressive drugs
Management of MG:
Medications: Cholinesterase inhibitors
What do these drugs do?
↑ neuromuscular transmission & muscle strength
Management of MG:
Medications: Immunosuppressive drugs
What is the drug? How is it used?
Azathioprine (off-label)
Management of MG:
Medications: Immunosuppressive drugs
Azathioprine (off-label)- What does this drug do?
May improve muscle strength
Suppress production of abnormal antibodies
Management of MG:
Non-drug measures include:
Thymectomy
Plasmapheresis
High doses of immunoglobulins
Management of MG:
Non-drug measures include:
Plasmapheresis - what is this?
Plasmapheresis ~ removal of abnormal antibodies
Management of MG
Self-care strategies
Proper nutrition
Adequate rest
Assistive devices
Coping strategies & support
Cholinesterase Inhibitors: What do they prevent?
Prevent degradation of acetylcholine by acetylcholinesterase (AChE or cholinesterase)
Cholinesterase Inhibitors:
Prevent degradation of acetylcholine by acetylcholinesterase (AChE or cholinesterase)
What does this lead to?
More ACh available; this can intensify transmission at virtually all Ach junctions
Cholinesterase Inhibitors
Cause More ACh available; this can intensify transmission at virtually all Ach junctions
What is the result of this?
Result: more acetylcholine to activate receptors –> enhances cholinergic action
Cholinesterase Inhibitors
Sufficient doses of Cholinesterase Inhibitors produce what?
Sufficient doses produce skeletal muscle stimulation
Cholinesterase Inhibitors
What responses do these drugs cause?
Muscarinic responses:
Neuromuscular Effects:
CNS:
Cholinesterase Inhibitors
Responses do these drugs cause:
Muscarinic responses:
bradycardia,
bronchial constriction,
urinary urgency,
increased glandular secretions,
increased GI tone & motility of smooth muscle,
miosis, & focusing lens for near visions
Cholinesterase Inhibitors
Responses do these drugs cause:
Neuromuscular Effects:
increase force of contraction but toxic doses reduce force of contractions because excessive amt of Ach at NMJ keep motor-end plate in state of constant depolarization
Cholinesterase Inhibitors
Responses do these drugs cause:
CNS: What do therapeutic effects produce? What do toxic levels cause?
CNS: therapeutic effects produce stimulation,
but toxic levels depress CNS if cross BBB
Cholinesterase Inhibitors
What kind of inhibitors exist?
Reversible & irreversible inhibitors
Cholinesterase Inhibitors
Reversible
Reversible (PO, IM, IV, Sq) – used for: MG, reversal of NM blocking agents in postops (pancuronium) & OD to reverse muscle relaxation & paralysis
Cholinesterase Inhibitors
Reversible: What is it caused by?
by causing accumulation of Ach
Cholinesterase Inhibitors
Irreversible
Irreversible (topical) – excessive muscarinic effects (cholinergic crisis)
Cholinesterase Inhibitors
Irreversible: How safe is it? What is it used for?
Highly toxic, used as insecticides, WWII used as nerve agents, warfare, terrorism
Lipid soluble – poisons agricultural workers
Cholinesterase Inhibitors
Irreversible:
What disease is it used for?
Used for glaucoma to stimulate muscarinic receptors on the ciliary and the sphincter muscle to contract to lower IOP
Cholinesterase Inhibitors used for Myasthenia Gravis
Mainstay of therapy
Neostigmine (bloxiverz, prostigmin) – PO, IM, IV, subQ
Pyridostigmine (mestinon) – PO
Cholinesterase Inhibitors used for Myasthenia Gravis
What do these drugs prevent?
Prevents acetylcholine inactivation so these agents intensify the effects of Ach released from motor neurons
Cholinesterase Inhibitors used for Myasthenia Gravis
What is the goal of treatment?
Goal: Muscle strength increases
Symptomatic relief
Cholinesterase Inhibitors used for Myasthenia Gravis
When is atropine given?
Atropine given if muscarinic responses excessive
Cholinesterase Inhibitors used for Myasthenia Gravis
How are initial doses?
Small initial doses
Cholinesterase Inhibitors used for Myasthenia Gravis
What are symptoms of improvement?
Sx of improvement:
ease of swallowing, increased ability to raise eyelids
Cholinesterase Inhibitors used for Myasthenia Gravis
What should patients be educated on?
Pt ed: monitor times of drug adm, when fatigue occurs, state of muscle strength before & after rx, sx of excessive muscarinic stimulation
Cholinesterase Inhibitors used for Myasthenia Gravis
When can patients modify their dose?
Pts can occasionally modify their dose (eg anticipation of exertion, supplemental doses 30-60 min before)
Cholinesterase Inhibitors used for Myasthenia Gravis
What are symptoms of undermedicated?
Sx of undermed: ptosis, difficulty swallowing
Cholinesterase Inhibitors used for Myasthenia Gravis
What are symptoms of overmedicated?
Sx of overmed:
excessive salivation & other muscarinic responses
Cholinergic Crisis:
What occurs?
Adverse effects/acute toxicity
Cholinergic Crisis:
Excessive muscarinic stimulation - What will accumulate?
SLUDGE & the Killer Bs
DUMBELS
Resp depression
Cholinergic Crisis:
Excessive muscarinic stimulation - What will accumulate:
SLUDGE & the Killer Bs:
(Salivation, Lacrimation, Urination, Diaphoresis/Diarrhea, GI cramps, Emesis, Bradycardia, Bronchospasm)
Cholinergic Crisis:
Excessive muscarinic stimulation - What will accumulate:
DUMBELS
DUMBELS (Diaphoresis/Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm, Emesis, Lacrimation, Salivation)
Cholinergic Crisis:
Excessive muscarinic stimulation - What will accumulate:
Resp depression from combo of depolarizing neuromuscular blockade & CNS depression
Cholinergic Crisis: What is treatment?
Treatment with antagonist [IV Atropine]
Cholinergic Crisis:
What does treatment with antagonist [IV Atropine] do?
Alleviate muscarinic effects of cholinesterase inhibition
Myasthenia Gravis (Cont.): What is treatment?
Treatment with cholinesterase inhibitors
Myasthenia Gravis (Cont.):
What are beneficial effects of this particular treatment?
Increased muscle strength
Myasthenia Gravis (Cont.):
Dosage adjustment?
Start small and adjust to patient response
Myasthenia Gravis (Cont.):
Dosage adjustment: How is timing of medication?
Timing is individualized to pt & is required around the clock to maintain blood levels
Myasthenia Gravis (Cont.):
Dosage adjustment: What should you teach patient?
Teach pt to modify dose depending on sx of over/under-medication
Myasthenic crisis and Cholinergic crisis
Cholinergic crisis: What is it characterized by?
Characterized by extreme muscle weakness or frank paralysis and signs of excessive muscarinic stimulation
Myasthenic crisis and Cholinergic crisis
Cholinergic crisis: What causes the extreme muscle weakness, paralysis and signs of excessive muscarinic stimulation?
Overstimulation at a neuromuscular junction, excess of acetylcholine (ACh), due to inactivity of acetylcholinesterase, which normally breaks down acetylcholine. The crisis is the result of patients with MG who take too much of their cholinesterase inhibitor
Myasthenic crisis and Cholinergic crisis
Cholinergic crisis: What is involved in treatment?
Treatment with respiratory support and atropine
Myasthenic crisis and Cholinergic crisis
Myasthenic crisis: What is it caused by?
Inadequate medication
Myasthenic crisis and Cholinergic crisis
Myasthenic crisis: What is it characterized by?
Extreme muscle weakness
Myasthenic crisis and Cholinergic crisis
Myasthenic crisis: What is it caused by?
Caused by insufficient ACh at the neuromuscular junction
Myasthenic crisis and Cholinergic crisis
Myasthenic crisis: What happens if left untreated?
Left untreated, myasthenic crisis can result in death as a result of paralysis of the muscles of respiration
Myasthenic crisis and Cholinergic crisis
Myasthenic crisis: What is used to relieve a crisis?
A cholinesterase inhibitor (such as neostigmine) is used to relieve the crisis
Myasthenia Gravis (Cont.)
Distinguishing myasthenic crisis from cholinergic crisis
History of medication use, or signs of excessive muscarinic stimulation assist with differential diagnosis
Challenging dose of edrophonium (tensilon)
Myasthenia Gravis (Cont.)
Distinguishing myasthenic crisis from cholinergic crisis
Challenging dose of edrophonium (tensilon): What is edrophonium?
Ultra-short acting cholinesterase inhibitor
Myasthenia Gravis (Cont.)
If edrophonium-induced elevation of acetylcholine levels alleviates symptoms, then the crisis is ___.
Myasthenia Gravis (Cont.)
If edrophonium-induced elevation of acetylcholine levels intensifies symptoms, the crisis is _____.
Myasthenia vs Cholinergic Crisis
Myasthenic Crisis: Causes of it?
Exacerbation of myasthenia following precipitating factors or failure to take drug as prescribed or drug dose too low
Myasthenia vs Cholinergic Crisis
Myasthenic Crisis: Differential diagnosis?
Improved strength after IV administration of anticholinesterase drugs
Myasthenia vs Cholinergic Crisis
Cholinergic Crisis: What are causes?
Overdose of anticholinesterase drugs, resulting in increased ACh (acetylcholine) at the receptor sites,
Myasthenia vs Cholinergic Crisis
Differential Diagnosis: What is differential diagnosis?
Weakness within 1 hr after ingestion of anticholinesterase drugs
Increased weakness of skeletal muscles manifesting as ptosis, dyspnea, effects on smooth muscle include pupillary miosis, salivation, diarrhea, nausea or vomiting, abdominal cramps, increased bronchial secretions, sweating, or lacrimation
