Pharm for the neuromuscular junction Flashcards
What is a cholinesterase inhibitor? How does it work?
- 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
What is a neuromuscualr junction nicotinic receptor antagonist?
- Sits in AChR and blocks transmission of electrical activity
- Reduces activity of neuromuscular junction
What is a glucocorticoid-sparing immunosuppressive drug?
- Alternate immunosuppressive drug than GCS. These alternative drugs usually take longer to have an immunosuppressive effect
What are the two cholinesterase inhibitors?
They can exist as:
- therapeutics (pyridostigmine neostigmine)
- Toxin (organophosphates)
What happens if an animal is exposed to organophosphates?
- Salivation
- lacrimation
- urination
- Diarrhoea
Is there an antidote for patients exposed to organophosphates?
Yes, an antidote for organophosphate toxicity is called pralidoxime or 2-PAM. It binds to the organophosphate releasing the AChE
Explain what is happening in this diagram (myasthenia gravis)
- 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
How would you diagnose Myasthenia gravis (MG)?
- 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
How would you treat MG?
You would use a longer acting cholinesterase inhibitor, these include:
- Pyridostigmine (mestinon)
- Neostigmine (prostigmin)
Other immunosuppressive drugs are also used in treatment
Give some examples of important immunosuppressive drug classes.
- Glucocorticosteroids (prednisolone, methylprednisolone, dexamethasone)
- Antimetabolites (azathioprine, mycophenolate, mofetil)
- alkylating agents (chlorambucil)
- Immuneophilin ligands (cyclosporine, tacrolimus)
Can the immunosuppressive drug asathioprine be used in cats?
No, an alkylating agent (chlorambucil) is used instead
What drug would you use to reverse antagonists of NMJ nicotinic receptors?
Cholinersterase inhibitor
What are the actions of Antagonists of NMJ nicotinic receptors?
- Muscular paresis/paralysis
- Not a therapeutic treatment
- Only used during general anaesthesia to assist with mechanical ventilation
What drug reverses the action of antagonists of NMJ nicotinic receptors?
Cholinesterase inhibitors
Why might botulinum toxin be used in veterinary medicine?
- Sometimes used to treat entropian, is releives skeletal muscle spasticity. Inhibits ACh release from presynaptic membrane at NMJ