Conditions Effecting the Nervous System and PharmacotherapyPart Seven: Neurodegenerative DX- Myasthenia Gravis MG

Question 1

Myasthenia Gravis MG:

What is the normal function of cholinesterase?

Answer 1

Normal function of cholinesterase is to break down ACh –> choline & acetic acid

Question 2

Myasthenia Gravis MG: What is it?

Answer 2

MG is a rare chronic, progressive autoimmune disease

Question 3

Myasthenia Gravis MG:
What occurs?

Answer 3

Antibodies destroy acetylcholine receptors (AChR) at post-synaptic membrane of neuromuscular junction

Question 4

Myasthenia Gravis MG:
What occurs:
Antibodies destroy acetylcholine receptors (AChR) at post-synaptic membrane of neuromuscular junction

What does this lead to?

Answer 4

Breakdown in the normal communication between nerves and muscles.

Question 5

Myasthenia Gravis MG:

What causes MG?

Answer 5

Cause: acquired immunological or genetic abnormality, thymic tumors or changes

Question 6

Myasthenia Gravis MG:

What are typical complaints?

Answer 6

Typical complaints:

muscle weakness,

ocular motor disturbances,

ptosis (droopy eyelid),

or diplopia are the initial symptoms.

Question 7

Myasthenia Gravis MG:

How is severity of weakness throughout the day?

Answer 7

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

Question 8

Myasthenia Gravis MG:

What does weakness involve?

Answer 8

Weakness can involve oropharyngeal and limb muscles.

Question 9

Myasthenia Gravis MG:

What is treatment for? Is there a cure?

Answer 9

There is no cure for MG, but treatment can help relieve signs and symptoms

Question 10

Prevalence and Exacerbating Factors of Myasthenia Gravis:

How common is it? Who is it in more?

Answer 10

Rare

More common in women

Question 11

Prevalence and Exacerbating Factors of Myasthenia Gravis:

Precipitating Factors for Exacerbations

Answer 11

Emotional stress

Pregnancy or menses

Trauma

Temperature extremes

Hypokalemia

Ingestion of drugs

Psychotropic drugs

Question 12

Prevalence and Exacerbating Factors of Myasthenia Gravis:

Precipitating Factors for Exacerbations:

Ingestion of what drugs can aggravate MG?

Answer 12

Ingestion of drugs, including aminoglycoside, macrolide, tetracycline & fluoroquinolone antibiotics, β-adrenergic & Ca++ ch blockers, and phenytoin aggravate MG

Question 13

Patho of MG:
What happens first?

Answer 13

Autoantibodies bind to the receptors at the NMJ, preventing acetylcholine from binding to them

Question 14

Patho of MG:
What happens after Autoantibodies bind to the receptors at the NMJ, preventing acetylcholine from binding to them?

Answer 14

Eventually autoantibodies attack specific receptors found at the neuromuscular junction

Question 15

Patho of MG:

Eventually autoantibodies attack specific receptors found at the neuromuscular junction

What does this cause?

Answer 15

Prevents muscle from responding to the nerve signal.

Question 16

Patho of MG

In MG, - antibodies bind & attack the acetylcholine (nicotinicM) receptors at the neuromuscular junction.

What happens to the number of sites?

Answer 16

Decreased ACh receptor sites at the NMJ

Question 17

Patho of MG

In MG, when there is a decreased number of acetylcholine receptor sites at the NMJ

What happens to the acetylcholine?

Answer 17

ACh can’t attach to receptors and induce muscle contraction

Question 18

Patho of MG

When ACh can’t attach to receptors and induce muscle contraction –>? What happens?

Answer 18

skeletal muscle weakness, and fatigue of the affected muscles.

Question 19

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?

Answer 19

The facial and ocular muscles are usually affected initially, followed by the arm and trunk muscles.

Question 20

Patho of MG:

What is acetylcholine responsible for normally?

Answer 20

Ach is responsible for movement.

Question 21

Patho of MG:

Normally, how is normal voluntary movement possible?

Answer 21

ACh moves across the neuromuscular junction to the nicotinicM receptors & makes voluntary movement possible.

Question 22

Patho cont’d:

90% of patients with generalized MG have what?

Answer 22

90% of patients with generalized MG have anti-acetylcholine receptor antibodies detectable in their blood.

Question 23

Patho cont’d:

What other disorders are common in patients with MG? What does this suggest?

Answer 23

Disorders of the thymus such as hyperplasia and tumors are common in patients with MG, suggesting autoantibody production occurs in the thymus.

Question 24

Clinical Presentation & DX of MG:

How do AchR receptor sites and autoantibody attacks occur?

Answer 24

AchR receptor sites and Ab attack varies

Question 25

Clinical Presentation & DX of MG: How is onset?

Answer 25

Insidious onset

Question 26

Clinical Presentation & DX of MG: What is first effected?

Answer 26

Face, throat & neck muscles 1st affected

Question 27

Clinical Presentation & DX of MG: Face, throat & neck muscles 1st affected What are the effects?

Answer 27

Facial drooping Throat muscles, esophagus: dysphagia Vision issues: Drooling, diff chewing & swallowing

Question 28

Clinical Presentation & DX of MG: Face, throat & neck muscles 1st affected What are the visual issues effects?

Answer 28

diplopia, ptosis, blurred vision, difficulty moving eyes

Question 29

Clinical Presentation & DX of MG: What are other effects?

Answer 29

Muscle fatigue after exercise Progressive weakness Dyspnea, impaired ventilation (severe MG)

Question 30

Clinical Presentation & DX of MG: When may symptoms first appear?

Answer 30

Sx may 1st appear in pregnancy, PP, or with anesthesia

Question 31

Clinical Presentation & DX of MG Diagnostics

Answer 31

PE & neuro assessment Serum antibody levels Nerve conduction study Electromyographic (EMG) studies Thymus CT, MRI Edrophonium Autoimmune testing

Question 32

Clinical Presentation & DX of MG Diagnostics: What is included in autoimmune testing?

Answer 32

ESR ACh receptor antibodies Antinuclear antibody

Question 33

Myasthenic Crisis: What is it?

Answer 33

Acute exacerbation

Question 34

Myasthenic Crisis: What is it characterized by?

Answer 34

Characterized by an increase in weakness and fatigue, and respiratory impairment may develop requiring ventilator support to maintain oxygenation.

Question 35

Myasthenic Crisis: How does it develop?

Answer 35

Develops as disease progresses

Question 36

Myasthenic Crisis: What happens to muscles?

Answer 36

Muscles too weak to maintain ventilation

Question 37

Myasthenic Crisis: There is Muscles too weak to maintain ventilation

Answer 37

Paralysis --> death Quadriparesis, quadriplegia --> resp arrest

Question 38

Myasthenic Crisis: Muscles too weak to maintain ventilation- why does this occur?

Answer 38

Caused by inadequate medication

Question 39

Myasthenic Crisis Exacerbating factors

Answer 39

Fatigue, illness, stress, pregnancy Extreme heat, emotional distress, infections EtOH consumption/med exposure/inadequate medication

Question 40

Myasthenic Crisis How is it treated?

Answer 40

TX with cholinesterase inhibitor

Question 41

Myasthenic Crisis TX with cholinesterase inhibitor includes what?

Answer 41

Neostigmine (Bloxiverz, Prostigmin), Pyridostigmine (Mestinon)

Question 42

Management of MG: Before patient takes PO meds, what must be assessed? How?

Answer 42

Assess swallow ability for PO Sips of H2O

Question 43

Management of MG: Medications

Answer 43

Cholinesterase inhibitors Immunosuppressive drugs

Question 44

Management of MG: Medications: Cholinesterase inhibitors What do these drugs do?

Answer 44

↑ neuromuscular transmission & muscle strength

Question 45

Management of MG: Medications: Immunosuppressive drugs What is the drug? How is it used?

Answer 45

Azathioprine (off-label)

Question 46

Management of MG: Medications: Immunosuppressive drugs Azathioprine (off-label)- What does this drug do?

Answer 46

May improve muscle strength Suppress production of abnormal antibodies

Question 47

Management of MG: Non-drug measures include:

Answer 47

Thymectomy Plasmapheresis High doses of immunoglobulins

Question 48

Management of MG: Non-drug measures include: Plasmapheresis - what is this?

Answer 48

Plasmapheresis ~ removal of abnormal antibodies

Question 49

Management of MG Self-care strategies

Answer 49

Proper nutrition Adequate rest Assistive devices Coping strategies & support

Question 50

Cholinesterase Inhibitors: What do they prevent?

Answer 50

Prevent degradation of acetylcholine by acetylcholinesterase (AChE or cholinesterase)

Question 51

Cholinesterase Inhibitors: Prevent degradation of acetylcholine by acetylcholinesterase (AChE or cholinesterase) What does this lead to?

Answer 51

More ACh available; this can intensify transmission at virtually all Ach junctions

Question 52

Cholinesterase Inhibitors Cause More ACh available; this can intensify transmission at virtually all Ach junctions What is the result of this?

Answer 52

Result: more acetylcholine to activate receptors --> enhances cholinergic action

Question 53

Cholinesterase Inhibitors Sufficient doses of Cholinesterase Inhibitors produce what?

Answer 53

Sufficient doses produce skeletal muscle stimulation

Question 54

Cholinesterase Inhibitors What responses do these drugs cause?

Answer 54

Muscarinic responses: Neuromuscular Effects: CNS:

Question 55

Cholinesterase Inhibitors Responses do these drugs cause: Muscarinic responses:

Answer 55

bradycardia, bronchial constriction, urinary urgency, increased glandular secretions, increased GI tone & motility of smooth muscle, miosis, & focusing lens for near visions

Question 56

Cholinesterase Inhibitors Responses do these drugs cause: Neuromuscular Effects:

Answer 56

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

Question 57

Cholinesterase Inhibitors Responses do these drugs cause: CNS: What do therapeutic effects produce? What do toxic levels cause?

Answer 57

CNS: therapeutic effects produce stimulation, but toxic levels depress CNS if cross BBB

Question 58

Cholinesterase Inhibitors What kind of inhibitors exist?

Answer 58

Reversible & irreversible inhibitors

Question 59

Cholinesterase Inhibitors Reversible

Answer 59

Reversible (PO, IM, IV, Sq) – used for: MG, reversal of NM blocking agents in postops (pancuronium) & OD to reverse muscle relaxation & paralysis

Question 60

Cholinesterase Inhibitors Reversible: What is it caused by?

Answer 60

by causing accumulation of Ach

Question 61

Cholinesterase Inhibitors Irreversible

Answer 61

Irreversible (topical) – excessive muscarinic effects (cholinergic crisis)

Question 62

Cholinesterase Inhibitors Irreversible: How safe is it? What is it used for?

Answer 62

Highly toxic, used as insecticides, WWII used as nerve agents, warfare, terrorism Lipid soluble – poisons agricultural workers

Question 63

Cholinesterase Inhibitors Irreversible: What disease is it used for?

Answer 63

Used for glaucoma to stimulate muscarinic receptors on the ciliary and the sphincter muscle to contract to lower IOP

Question 64

Cholinesterase Inhibitors used for Myasthenia Gravis Mainstay of therapy

Answer 64

Neostigmine (bloxiverz, prostigmin) – PO, IM, IV, subQ Pyridostigmine (mestinon) – PO

Question 65

Cholinesterase Inhibitors used for Myasthenia Gravis What do these drugs prevent?

Answer 65

Prevents acetylcholine inactivation so these agents intensify the effects of Ach released from motor neurons

Question 66

Cholinesterase Inhibitors used for Myasthenia Gravis What is the goal of treatment?

Answer 66

Goal: Muscle strength increases Symptomatic relief

Question 67

Cholinesterase Inhibitors used for Myasthenia Gravis When is atropine given?

Answer 67

Atropine given if muscarinic responses excessive

Question 68

Cholinesterase Inhibitors used for Myasthenia Gravis How are initial doses?

Answer 68

Small initial doses

Question 69

Cholinesterase Inhibitors used for Myasthenia Gravis What are symptoms of improvement?

Answer 69

Sx of improvement: ease of swallowing, increased ability to raise eyelids

Question 70

Cholinesterase Inhibitors used for Myasthenia Gravis What should patients be educated on?

Answer 70

Pt ed: monitor times of drug adm, when fatigue occurs, state of muscle strength before & after rx, sx of excessive muscarinic stimulation

Question 71

Cholinesterase Inhibitors used for Myasthenia Gravis When can patients modify their dose?

Answer 71

Pts can occasionally modify their dose (eg anticipation of exertion, supplemental doses 30-60 min before)

Question 72

Cholinesterase Inhibitors used for Myasthenia Gravis What are symptoms of undermedicated?

Answer 72

Sx of undermed: ptosis, difficulty swallowing

Question 73

Cholinesterase Inhibitors used for Myasthenia Gravis What are symptoms of overmedicated?

Answer 73

Sx of overmed: excessive salivation & other muscarinic responses

Question 74

Cholinergic Crisis: What occurs?

Answer 74

Adverse effects/acute toxicity

Question 75

Cholinergic Crisis: Excessive muscarinic stimulation - What will accumulate?

Answer 75

SLUDGE & the Killer Bs DUMBELS Resp depression

Question 76

Cholinergic Crisis: Excessive muscarinic stimulation - What will accumulate: SLUDGE & the Killer Bs:

Answer 76

(Salivation, Lacrimation, Urination, Diaphoresis/Diarrhea, GI cramps, Emesis, Bradycardia, Bronchospasm)

Question 77

Cholinergic Crisis: Excessive muscarinic stimulation - What will accumulate: DUMBELS

Answer 77

DUMBELS (Diaphoresis/Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm, Emesis, Lacrimation, Salivation)

Question 78

Cholinergic Crisis: Excessive muscarinic stimulation - What will accumulate:

Answer 78

Resp depression from combo of depolarizing neuromuscular blockade & CNS depression

Question 79

Cholinergic Crisis: What is treatment?

Answer 79

Treatment with antagonist [IV Atropine]

Question 80

Cholinergic Crisis: What does treatment with antagonist [IV Atropine] do?

Answer 80

Alleviate muscarinic effects of cholinesterase inhibition

Question 81

Myasthenia Gravis (Cont.): What is treatment?

Answer 81

Treatment with cholinesterase inhibitors

Question 82

Myasthenia Gravis (Cont.): What are beneficial effects of this particular treatment?

Answer 82

Increased muscle strength

Question 83

Myasthenia Gravis (Cont.): Dosage adjustment?

Answer 83

Start small and adjust to patient response

Question 84

Myasthenia Gravis (Cont.): Dosage adjustment: How is timing of medication?

Answer 84

Timing is individualized to pt & is required around the clock to maintain blood levels

Question 85

Myasthenia Gravis (Cont.): Dosage adjustment: What should you teach patient?

Answer 85

Teach pt to modify dose depending on sx of over/under-medication

Question 86

Myasthenic crisis and Cholinergic crisis Cholinergic crisis: What is it characterized by?

Answer 86

Characterized by extreme muscle weakness or frank paralysis and signs of excessive muscarinic stimulation

Question 87

Myasthenic crisis and Cholinergic crisis Cholinergic crisis: What causes the extreme muscle weakness, paralysis and signs of excessive muscarinic stimulation?

Answer 87

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

Question 88

Myasthenic crisis and Cholinergic crisis Cholinergic crisis: What is involved in treatment?

Answer 88

Treatment with respiratory support and atropine

Question 89

Myasthenic crisis and Cholinergic crisis Myasthenic crisis: What is it caused by?

Answer 89

Inadequate medication

Question 90

Myasthenic crisis and Cholinergic crisis Myasthenic crisis: What is it characterized by?

Answer 90

Extreme muscle weakness

Question 91

Myasthenic crisis and Cholinergic crisis Myasthenic crisis: What is it caused by?

Answer 91

Caused by insufficient ACh at the neuromuscular junction

Question 92

Myasthenic crisis and Cholinergic crisis Myasthenic crisis: What happens if left untreated?

Answer 92

Left untreated, myasthenic crisis can result in death as a result of paralysis of the muscles of respiration

Question 93

Myasthenic crisis and Cholinergic crisis Myasthenic crisis: What is used to relieve a crisis?

Answer 93

A cholinesterase inhibitor (such as neostigmine) is used to relieve the crisis

Question 94

Myasthenia Gravis (Cont.) Distinguishing myasthenic crisis from cholinergic crisis

Answer 94

History of medication use, or signs of excessive muscarinic stimulation assist with differential diagnosis Challenging dose of edrophonium (tensilon)

Question 95

Myasthenia Gravis (Cont.) Distinguishing myasthenic crisis from cholinergic crisis Challenging dose of edrophonium (tensilon): What is edrophonium?

Answer 95

Ultra-short acting cholinesterase inhibitor

Question 96

Myasthenia Gravis (Cont.) If edrophonium-induced elevation of acetylcholine levels alleviates symptoms, then the crisis is ___.

Question 97

Myasthenia Gravis (Cont.) If edrophonium-induced elevation of acetylcholine levels intensifies symptoms, the crisis is _____.

Question 98

Myasthenia vs Cholinergic Crisis Myasthenic Crisis: Causes of it?

Answer 98

Exacerbation of myasthenia following precipitating factors or failure to take drug as prescribed or drug dose too low

Question 99

Myasthenia vs Cholinergic Crisis Myasthenic Crisis: Differential diagnosis?

Answer 99

Improved strength after IV administration of anticholinesterase drugs

Question 100

Myasthenia vs Cholinergic Crisis Cholinergic Crisis: What are causes?

Answer 100

Overdose of anticholinesterase drugs, resulting in increased ACh (acetylcholine) at the receptor sites,

Question 101

Myasthenia vs Cholinergic Crisis Differential Diagnosis: What is differential diagnosis?

Answer 101

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