Cholinergic Agonists Flashcards
What is cholineacetyl transferase?
Enzyme that produces acetylcholine
Where is cholineacetyl transferase ound?
Corneal epithelium, iris, ciliary body, inner plexiform layer
Where is cholinesterase foudn in high concentration?
Iris and ciliary body sphincter muscles
But not in aqueous, vitreous or retinal vessels
Where are muscarinic receptors present?
Iris, ciliary body, retina
What are direct acting muscarinic agonists? Indirect acting? Examples
Direct acting - stimulate muscarinic receptors directly E.g. pilocarpine
Indirect acting - cholinesterase inhibitor by phosphoylation or by carbamylation physostigmine, pyridostigmine, demecarium, echothiopate
Both:
E.g. Carbachol
What actions to muscarinic agonists cause?
Miosis (stimulating iris sphincter muscle)
Accomomodation (stimualting ciliary muscle)
Decreased IOP (passive increase in aq outflow)
What are the uses of cholinergic agnoists?
Treating POAG and preventing AACG
Accommodative squints (decreasing the accommodative effort)
What mydriasis will pilocarpine reverese?
Reverse phenylephrine will be reversed
Atropine will not
What is used to diagnose Adie’s pupil
Pilocarpine 0.125% - very sensitive - will cause miosis
What are side effects of cholinergic agonists
Headache
Brow ache
How does echothiopate act?
Indirect muscarinic agonist
Inhibit cholinesterase by phosphorylation
How doees physostigmine act?
Indirect muscarinic agonist
Inhibit cholinesterase by carbamylation
Why does adding pilocarpine to a indirect acting muscarinic agonists?
Decrease miosis
As acetylcholine is more potent than pilocarpine
What are the effects on pressure of indirect acting muscarinic agonists?
IAMAProduce initian rise in intraocular pressure and evenutal hypotensive effect
What are the uses of indirect muscarinic agonists?
POAG
AACG
What are side effects of indirect muscarinic agonist?
Cataract
Hyperplasia of the iris pigment epithelium
How do muscarinic antagonists work? E.g.
Compete with acetylcholine for receptor sites on the post-synaptic membrane
Tropicamide
Atropine
Cyclopentolate
Homatropine
Mydriatic effect by inhibiting iris sphincter muscle
Also cause inihibition of ciliary muscles resulting in cycloplegia
Why does tropicamide have longer duration of action in pigmented eyes?
Binding of drugs by pigment accounts for decreased efficacy and latency of action in pigemented eyes
How does atropine supplement antimuscarinic action?
Stimulating alpha adrenergic receptors on dilator muscles
What are side effects of muscarinic antagonists?
Mild fever
Skin flushing
Can raise IOP through angle closure
May decrease aqueous outflow
Increased distension and risk of necrotising enterocolitis in neonates
Ataxic dysarthria, cerebellar signs
Increased risk fo seizures
Tachyarrhythmias
What is the MOA of pyridostigmine? Physostigmine? Ecothiopate
Acetylcholinesterase inhibitor - increases availbility of ACh at NMJ
Half life of 6h
Physostigmine has a very short half life
Ecothiopate - long acting AChesterase inhibitor - irreversible can cause life threatening prolonged paralysis
How does pilocarpine work?
Increased trabeculor outflow
Facilitaes aqueous drainage by constricting the iris and opening the meshwork from its action on ciliary muscle
Why is pilocarpine CI in aqueous misdirection?
Contraction of ciliary muscle can lead to
Induced myopia
Forward displacement of the lens-iris diaphragm
When is pilocarpine CI in angle closure? What is the treatment in these cases?
AC secondary to topiramate where aetiology is forward lens-iris diaphragm rotation
Preferred treatment is atropine which relaxes the ciliary body and allows lens-iris diaphragm to rotate posteriorly
