Pharm for the neuromuscular junction

Question 1

What is a cholinesterase inhibitor? How does it work?

Answer 1

• Binds to AChesterase at NMJ (and other Ach receptor sites)
• Peripherally leads to increase electrical firing at the NMJ – often manifested as skeletal muscle twitching

Question 2

What is a neuromuscualr junction nicotinic receptor antagonist?

Answer 2

• Sits in AChR and blocks transmission of electrical activity
• Reduces activity of neuromuscular junction

Question 3

What is a glucocorticoid-sparing immunosuppressive drug?

Answer 3

• Alternate immunosuppressive drug than GCS. These alternative drugs usually take longer to have an immunosuppressive effect

Question 4

What are the two cholinesterase inhibitors?

Answer 4

They can exist as:
- therapeutics (pyridostigmine neostigmine)
- Toxin (organophosphates)

Question 5

What happens if an animal is exposed to organophosphates?

Answer 5

• Salivation
• lacrimation
• urination
• Diarrhoea

Question 6

Is there an antidote for patients exposed to organophosphates?

Answer 6

Yes, an antidote for organophosphate toxicity is called pralidoxime or 2-PAM. It binds to the organophosphate releasing the AChE

Question 7

Explain what is happening in this diagram (myasthenia gravis)

Answer 7

• Immune mediated attack on the nicotinic receptors
• In MG, antibodies are produced that binds to, & blocks NMJ AChR (acetylcholine receptor). Therefore fewer binding sites for ACh, has an effect on the signal getting through to the muscles
• Leads to accelerated AChR endocytosis & degradation
• Activate complement that damages muscle fibres

Question 8

How would you diagnose Myasthenia gravis (MG)?

Answer 8

• Use a cholinesterase inhibitor - binds to NMJ AChE allowing Ach longer action at the fewer nicotinic receptors that are available due to antibody attack
• Edrophonium - tensilon - short acting diagnostic drug

Question 9

How would you treat MG?

Answer 9

You would use a longer acting cholinesterase inhibitor, these include:
- Pyridostigmine (mestinon)
- Neostigmine (prostigmin)

Other immunosuppressive drugs are also used in treatment

Question 10

Give some examples of important immunosuppressive drug classes.

Answer 10

• Glucocorticosteroids (prednisolone, methylprednisolone, dexamethasone)
• Antimetabolites (azathioprine, mycophenolate, mofetil)
• alkylating agents (chlorambucil)
• Immuneophilin ligands (cyclosporine, tacrolimus)

Question 11

Can the immunosuppressive drug asathioprine be used in cats?

Answer 11

No, an alkylating agent (chlorambucil) is used instead

Question 12

What drug would you use to reverse antagonists of NMJ nicotinic receptors?

Answer 12

Cholinersterase inhibitor

Question 13

What are the actions of Antagonists of NMJ nicotinic receptors?

Answer 13

• Muscular paresis/paralysis
• Not a therapeutic treatment
• Only used during general anaesthesia to assist with mechanical ventilation

Question 14

What drug reverses the action of antagonists of NMJ nicotinic receptors?

Answer 14

Cholinesterase inhibitors

Question 15

Why might botulinum toxin be used in veterinary medicine?

Answer 15

• Sometimes used to treat entropian, is releives skeletal muscle spasticity. Inhibits ACh release from presynaptic membrane at NMJ