Eye pharmacology Flashcards
What is the basis of phototransduction
Opsin receptors - what are these
- Receptors for the light
- Rhodopsin - present in highly sensitive rods.
- In the cones (red, green, blue cones now known as long/medium/short wave sensitive) we have different opsins.
Retinoids
nUmber system important to define versions of retinol and retinal
All-trans-retinol = all 4 double bonds are trans.
- Retinal - in context of vision
Rhodopsin structures
- Rhodopsin = protein and chromophore
- Potoein (an apoprotein -word that reflects the fact that for overall structure it needs more than protein and when bound to chromophore its then the apoprotein ) = Opsin. 7 transmembrane domains
- Chromophore = 11-cis retinal - covalently bound to lysine (K296)
- The particular amino acid of sequence - a lysine with amine group a nd this is point which retinal is covalently bound.
Schiff base in rhodopsin
Response to light of retinal by itself (11-cis-retinal) -> all-trans-retinal
Steric change in retinal (11-cis to all-trans) leads to structural reconfiguration of rhodopsin, including cytoplasmic domains -> signalling -> light perception
STRUCTURAL CHANGE -> FUNCTIONAL CHANGE
Response to light of rhodopsin
Transducin
Transducin (Gt) is a protein naturally expressed in vertebrate retina rods and cones and it is very important in vertebrate phototransduction. It is a type of heterotrimeric G-protein with different α subunits in rod and cone photoreceptors.
Transducin (Gt) comprises 3 subunits:
- a-GTPase =
- Binds GDP in inactive state
- binds GTP in active state
- N-terminal lipid link to membrane
- C-terminal interacts with rhodopsin
- B-regulatory subunit
- y-regulatory subunit -> c terminal lipid link tp membrane
B-regulatory and y-regulatory form ssingle funcitonal unit
- Rhodopsin activates transducin:
- Light acitvation results in release of GDP and bidning of gTP to Gta
- GTP-bound Gta activates downstream signalling-> cGMP phosphodiesterase
G-Protein coupled receptors - signalling cycle
Need to know
G-protein signalling in general
Link between b receptors and rhodopsin
Retinoids - drugs
Retinoid drugs exert there effects through receptors:
Make connection that these are virtually same moelcule as what we talked about but exert biological effect and some used in acne
Mydriasis vs miosis
Horners syndrome of a cat
What controls the size of the pupil? and the innervation of muscles
MOstly a balnce of tones
Atropine
synechiae - connections between back iris and front lens often driven by inflammation and it really pulls iris out of way if inflammation in iris an minimised chance of producing connective tissue connections,
Cyclopentolate
Tropicamide
Phenylephrine
Other eye drugs for drug-induced mydriasis
- Hyoscine butylbromide
- L-dopa
- Cocaine
*
Diamorphine (heorin)
Small pinpoint pupils htought to be primarily by action in CNS stimulating nuclei oculomotor
Pyridostigmine
Novichok poisoning - nerve agents
Malathion
Ciliary Muscles
Cardiac and msooth muscl e
In cardiac muscle with B1 receptors, get increased rate and force contraction through activation cAMP->PKA + HCN channels…
But in smooth muscle then with b2 receptors pKA phosphorylates MLCK -> MLCK-P which is less active and this is what drioves contraction.
Smooth muscle contraction
Smooth muscle relaxation
Turning contraction fo smooth muscles back on again after relaxation
How does theophylline cause bronchial smooth muscle relaxations
Phosphodiesterase inhibitors and vision
Basic anatoym of glaucoma
WHat is Glaucoma
- Visua impairment - progressive optic neuropathy, optic nerve cupping
- Classification:
- Primary vs ssecondary
- Acute vs chronic
- Open-angle cs closed-angle (open is ‘normal’ configuration)
- Primary open-angle glaucoma (POAG) is most common form (and chronic)
- intra-ocular pressure (IOP) often raised- significant risk factor
- IOP regulated by production and drainage of aqueous humour:
- Impaired damage (decreased outflow) is common cause raised IOPIncreased production (Increased inflow) is rare cause of raised IOP
Production of aqueous humour
Ciliary body - the muscles, epithelia, stroma, vessels and nerves
DOuble epithelia of ciliary processes
Glaucoma pharmacotherapy
Glaucoma drugs listed
Prostaglandins MOA
Revision on prostagandins
B blockers in Glaucoma
Apraclonidine
Clonidine
Adrenoreceptor classification and signalling
Acetazolamide
Acetaxolamide and pic of physiology
Carbonic anhydrase in ciliary processes
Dorzolamide
Pilocarpine
Age related macular degeneration what is it
VEGF
Bevacizumab (not licensed use in macular degeneration but can be used)
Ranibuzumab
Aflibercept
