12.1.2 Myasthenia Gravis

Question 1

What is myasthenia gravis?

Answer 1

Autoimmune condition where ACh has difficulty binding due to IgG blockage of the binding site

ACh rarely binds and gets broken down by AChE

Question 2

What is myasthenia gravis characterised by?

Answer 2

• Fluctuating
• Fatiguable
• Weakness in skeletal muscles

Question 3

What does fatiguable in myasthenia gravis mean?

Answer 3

• As person uses their muscles over the next few minutes it fatigues as ACh is depleted
• Stopping for a few minutes allows for recovery of ACh
• Also means worse when tired too

Question 4

What weakness in skeletal muscles are present in myasthenia gravis?

Answer 4

Extraocular muscles

Bulbar involvement
- Dysphagia
- Dysphonia
- Dysarthria (speech)

Limb weakness
- Proximal symmetric

Respiratory muscle involvement
- Eventually causes death

Question 5

What drugs affect neuromuscular transmission?

Answer 5

Myasthenia Gravis ABCS Please

Magnenisum
Aminoglycosides
ACEi
Beta blockers
CCBs
Succinylcholine
Penicillamine and chloroquine

Exacerbates myasthenia gravis

Question 6

What are the complications of myasthenia gravis?

Answer 6

Acute exacerbation
Myasthenic crisis
- Respiratory failure, dysphagia, DVT if immobile, aspiration
- Need to support ABC

Overtreatment
Cholinergic crisis
- Muscle paralysis

Both present the same

Question 7

What is the therapeutic management of myasthenia gravis?

Answer 7

• Acetylcholine esterase inhibitors symptomatic management
• Corticosteroids - decrease immune response
• Steroid sparing - Azathioprine
• IV immunoglobulin
• Plasmapheresis - removes AChR antibodies

Question 8

How do AChE inhibitors work?

Answer 8

• Stop ACh being broken down
• Enhances neuromuscular transmission
• Skeletal and smooth muscle
• Excess dose can cause depolarising block - cholinergic crisis
• Muscarinic side effects

Question 9

Give examples of acytylcholine esterase inhibitors

Answer 9

Pyridostigmine
Oral

Neostigmine
Oral and IV preps for ITU (quicker, duration 4hrs, significant antimuscarinic side effects)

Question 10

What are the pharmacokinetics of pyridostigmine?

Answer 10

Onset - 30 mins
Peak 60-120 mins
Duration - 3-6hrs
Dose and interval timing crucial, need to have at least 30 minutes before food (NOT ON NORMAL DRUG ROUND)

Question 11

What are the muscarinic side effects of AChEis?

Answer 11

SLUDGE
Salivation
Lacrimation
Urination
Diarrhoea
GI upset and hypermotility
Emesis