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52 Cards in this Set
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Drug to treat OAG |
Prostaglandin Analogues: Latanaprost Tafluprost Travoprost |
Prost: apart from Bimatoprost |
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Drug to treat OAG |
Prostamide analogues: Bimatoprost |
Prost |
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Drug to treat OAG |
Beta blockers: Timolol Betaxolol Cartelol Levobunolol |
LOL TBCL: To Be Confirmed Love |
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Drugs to treat OAG & CAG |
Carbonic Anhydrase Inhibitors Acetazolmide Dorzolomide Brinzolomide |
..."olomide |
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Drugs to treat OAG & CAG |
Alpha 2 agonists (sympathomimetics) Brimonidine Apraclonidine |
.."onidine |
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Drugs to treat CAG |
Parasympathomimetics: Pilocarpine Hcl Pilocarpine Nitrate |
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Drugs to treat CAG |
Hyperosmotic agents |
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MoA Prostaglandin analogue |
Increases uveoscleral outflow Produced naturally in most cells, biggest class of glaucoma drugs as lower IOP by 35%, long duration of action so applied once at night and good tolerability. Also have anti inflammatory effect too. All analogues of Prostaglandin F2a isopropyl ester rather than P E2 These act through PGF2a recept aka FP receptor. Its Gaq coupled so activates PLC which converts PIP2 into diacyl glycerol (DAG) & IP3 (inositol triphosphate).
FP receptors found on ciliary muscle, iris sphincter, TMeshwork and small amount on sclera |
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Explain Maxtrix mettalloproteinases (MM) |
P.glandin analogues able to increase uveoscleral outflow by remodelling scleral structure so it's more meshlike by increasing MM (these are able to degrade collagen/extracellular matrix found bw cells so therefore it decreases resistance b/w cilliary muscle / sclera so it'll increase aqueous outflow |
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Active drug form
Short half life Can't be used on eye |
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Latanprost |
Prostaglandin analogue 0.005% generic 0.005% Xalatan M + BAK |
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Tafluprost |
Prostaglandin analogue Travoltan 40 ug/ml M + propylene glycol |
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Travoprost |
Prostaglandin analogue Saflutan 15 ug\ml S dose form only |
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Prostaglandin analogues used = prodrugs ➡️ what are prodrugs ? |
Prodrugs can be applied to eye as not in active form Their ester group has to be metabolised and converted into acid group before it can bind to receptor and take effect |
BVs |
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Prodrugs prostaglandin analogues (Latanprost/Tafluprost/Travoprost) side effects ... Short term ? |
Initially, red eye due to vasodilation and oedema but this (wears off quickly) |
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Prodrugs prostaglandin analogues (Latanprost/Tafluprost/Travoprost) side effects ... LONG TERM ? |
Increases in: pigmentation of iris, eyelash growth - can appear strange if IOP high in one eye only Irreversible iris hyperpigmentaion happens in quarter of pxs after 6 months of use of drugs - highest incidence in green brown irises bc have increase in no of pigmented granules in stroma rather than increase in no of melanocytes Can gt hyperpigmentaion of periocular skin but this reversible
Contraindicated in pregnancy even tho theoretical risk of cell division we don't want to take any risks in pregnancy May precipitate / worsen cystoid macular oedema seen via preoperative use of the drugs after cataract surgery and in aphakic eyes |
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Another example of PAnalogue? |
Binatoprost Analogues of PGF2a 1-ethanolamide
Lumigan 100 or 300 ug/ml M + BAK Shown to have greater effect on lowering IOP than the other PAnalogues in studies but causes more conjunctival hyperaemia but fewer HAs & perhaps less iris hyperpigmentation |
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Bimatoprost side effects / efficacy ? |
Same as prostaglandin analogues |
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What are BBlockers? Including MSA & ISA |
Decreases aqueous humour production They have membrane stabilising activity which are local anaesthetic effects e.g. Propanolol (drug not used in ocular condts) They also have Intrinsic sympathomimetic activity = partial agonism not full agonism e.g. Cartelol (dug not used in ocular conts)
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Describe BB being antagonists at b1 and b2 receptors .. |
They are antagonists at b1 & b2 recpetors b1 = Heart, kidney and causes vasoconstriction in BVS - so contraindicate din anyone with heart failure/heart block b2 = Lungs; bronchioles - so contraindicated in anyone w/asthma/chronstructive airway disease In Eye: when b2 activated causes aq humour secretion bc it stimulates cilliary epithelium cells when this happens see 2 effects: (1) Activates Na+/K+/2 Cl- co transporter in pigmented epithelium cells (2) Non-pigm.epithelium cells stimulates Cl- efflux so increases aq humour production via osmosis |
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Draw and describe BB MoA |
BB treat OAG / lower IOP bc decrease aq humour production mediated by affecting cililary epithelium cells (CEC) Agonists of B2 recptors on CEC cause aq production / secretion. These are mechanisms that lower IOP.
B2 receptor activation stimulates CAMP which regulates ion transport in CE CAMP activates Na+/K+/2Cl- co transporter in pigmented epithelium cells & stimulates Cl- efflux in non-pigmented epithelium cells Stimulation of Cl- transporter increases aq humour production via osmosis and BB PREVENT this from happening thus they decrease aq humour production
*Insert diag* Diag shows CEC (pigmented or non pigmented) When NA binds to beta 2 adrenoreceptor it works through Gs protein coupled receptor so we get ⬆️ in CAMP through activation of adenylyl cyclase CAMP has positive effect so it'll increase Na+/K+/2Cl- cotransporter activity do any of ions coming into cell will be thrown out of the water ie efflux and water will follow down osmotic gradients This causes increases aq humour production BB are antagonists at b2 receptor so prevent NA from binding thus decrease ion excretion from cells meaning less aq humour is made |
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Describe Timolol .. |
Beta blocker Timoptol 0.25% or 0.50% Timoptol LA 0.25% or 0.50% (Both M + BAK) Myogel 0.1% (M+benzododecium br) Tiopex (unit dose gel)
Timolol = levobunolol > Cartelol Tiopex = gel so good contact time in conjunctival sac |
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Describe Betaxolol ... |
BBlocker Betoptic drops 0.5% BAK Betoptic suspension 0.25% single use BAK/EDTA Betaxolol b1 selective not that good at lowering IOP but has calcium blocking activity albeit good contact time bc molecules bind ironically to ocular surface |
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Describe Cartelol .. |
BBlocker Teoptic 1 or 2% BAK Least lipophillic bc doesn't cross BBB barrier ➡️ less CNS side effects |
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Describe Levobunolol ... |
BBlocker Betagan 0.5% Single use 0.5% BAK Good contact time as formulated in polyvinyl alcohol |
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BBlocker advantages |
Very well tolerated Rapid onset of action Compatible w other drugs Effective in 75% pxs Lowers IOP by 20% (but not as good as P/glandin analogues as that lowers by 35%) Overall advantage if monoc treatment of IOP use BB over PAnalgoues bc avoids cosmetic disadvantage of asymmetrical lash growth/periocular pigmentation |
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BBlocker disadvantages ... |
Px compliance: one drop 2-3 xs daily Efficacy drops over time 👎🏽☹️ Only to be used in morning when we sleeping have low heart rate these drugs lower BP of px so may impact ONH perfusion ie exacerbates nocturnal bradycardia |
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BBlocker side effects |
Cardiovascular- causes bradycardia, hypotension, peripheral vasoconstriction (avoid on pxs w peripheral vascular disease eg Raynaud phenomenon), impotence. Contraindicated for anyone w heart block / heart failure thus pulse needs to be checked before prescription of drug Bronchial - affects lungs causes bronchoconstriction so contraindicated in anyone w asthma & chronic airway diseases thus need to check history of px thoroughly Diabetics - masks hypoglycaemia so avoid if diabetic |
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Advantages of Bb fixed dose combos? |
Very effective Avoids 2nd drop washout effect Only one drug w preservative rather than two drugs w 2 preservatives Cost effective to px and NHS |
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CAIs MoA?.. |
CAI inhibit carbonic anhydrase enzyme in ciliary epithelium (also present in body / high concentrations in kidney) which catalyses following/ CO2+H2O 🔁 H2CO3 🔁 H+ + HCO3- Biocarbonate ion formation needed for aq secretion so inhibition of carbonic anhydrase reduces aq formation / secretion thus lowers IOP
*insert diag* Diag shows Na+ & Cl- ions coming into cell but due to CAI carbon dioxide & water do not convert into hydrogen and biocarbonate ions so these ions are not getting secreted out if cell Thus osmotic gradient not as high so get reduction in production of aq humour Here we get decreased biocarb ion secretion but doesn't affect amount of sodium, chloride and potassium passing through cotransporter CAIs similar to BB ie affect ion transport / secretion within CEC but done in diff ways |
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Describe Acetazolmide .. |
CAIs Only systemic as lipophillic so can't be applied on eye Diamox Diamox, Sr IV, tablets or capsules EMERGENCY treatment only Nasty side effects: allergic/blood disorders as suflonamide derivative CAIs found all over body so it can cause gastrointestinal, diuresis, acid base balance disturbances as well as CNS effects: depression, drowsiness and parasthesias; pins and needles
So defo only limtd to systemic emergency use |
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Describe Brinzolomide and Dorozolamide ... |
CAIs Topical ONLY as less lipophillic than Acetazolmide 😌 Not sole therapy used w BB or prostg analogueswhich is good as lowers IOP by 20% (but not as effective as PAnalogues which lower it by 35%)
Brinzolomide: Azopt 10 mg\ul -1drop 2xs day Dorozolamide: Trusopt 2% - 1 drop 2-3 xs day (M +BAK)
Even tho can apply topically so has good lipid solubility so allows corneal absorption can cause transient burning and stinging ..this is bc pH brinzolomide drops 7.5 and pH dorzolomide 5.6 - 6.0
Allergic conjunctivitis, bleph, transient myopia
Assoc w taste disturbances: nasty taste, dry mouth, HAs |
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Describe Alpha2 agonists ... |
A2 receptors found in cilliary epithelial cells They are -ively coupled to G proteins: Gi protein. Inhibits Adenylate cyclase activity so ⬇️ CAMP levels when agonist binds So ⬇️ activity of Na K Cl co transporter which reduces amount of ions going out of cell this less osmotic gradient and less aq humour produced |
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Describe the 2 Alpha 2 agonists drugs |
Decreases aqueous outflow Brimonidine: selective for a2 receptors peak effect 2 hours. 1 drop 2 X day
Apraclonidine: less selective for a2 receptors has activity on other receptors and only short term use as causes taphylaxis: sensitisation of receptors and stops binding of agonists So limtd use only use after surgery ie after laser surgery NOT FOR CHRONIC USE 1 drop 3 xs day max use 1 month |
End in ..idine |
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Describe Alpha 2 agonist drugs: Brimonidine and Apraclonidine side effects... Local and systemic side effects |
Local: transient stinging and burning , blurred vision and photophobia
Systemic: drowsiness, dry mouth and taste disturbances |
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Compare BB MoA w A2 agonists |
Bb positively coupled to G protein; Gs coupled so won't inhibit Adenylate cyclase Increases CAMP levels when agonists binds |
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G protein A2 receptors? |
Gi - inhibits Adenylate cyclase ⬇️ CAMP levels ⬇️ activity of Na K Cl co transporter Etc ... |
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Describe Parasympathomimetics: Pilocarpine Nitrate & Pilocarpine HCl |
P/nitrate Minims 2% P/Hcl 1,2,4% generic - effects last 6 hours so applied 1 drop 4 xs day and done bc has cyclical effect on IOP |
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Side effects of Parasymp.mimetic Pilocarpine HCl |
Decreases IOP by 10% when used in conjunction w other drugs May precipitate AACG Fluctuating vision Cilliary spasm |
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MoA Pilocarpine Hcl |
(Parasympathomimetic) Agonist at M3 receptor coupled to Gq so ⬇️ IP3 & DAG Causes cilliary muscle to contract ..pulls on scleral spur so opens TM and thus releases aq humour so reduces IOP |
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Prostaglandin analogues G protein? |
Gaq - assoc w IP3 DAG and PLC |
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Describe hyperosmotic agents |
Treats CAG Increases osmolarity of blood so gets rid of fluid and reduces IOP over time |
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Describe future glaucoma drugs .. Latanoprostene (Vesone |
Is PGE2a (prostaglandin analogue) compound w NO element Works by increasing aq humour outflow by relaxing TM cells Complimentary mechanism on conventional & uveoscleral pathways |
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Describe future glaucoma drug: RHO Kinase (ROCK) inhibitors ... |
Phase II/III trials (near end of drug production) Works bc reduces cellular stiffness by reducing contractility also has anti inflam effects Rhopessa drug - furthest in clinical drug trials both ROCK & NET (Noradrenaline transport) inhibitor |
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Describe future glaucoma drug: antibodies against human growth factor |
Works bc can bind to human growth factor / aqueous so prevents scar tissue formation |
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Parasympathomimetic: Pilocarpine Hcl G protein? |
Gq coupled so decreases IP3 & DAG Stimulates ciliary muscle so pulls on scleral splur opens TM and releases aq humour so reduces IOP |
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What is the IOP circadian rhythm? |
IOP changes throughout day At night in supine position highest bc of ⬆️ in episcleral venous pressure IOP goes through trough at 9.30 pm, peaks at 5.30 am & reduces throughout |
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Main routes of aq outflow ? |
2 = TM & uveoscleral outflow |
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What are two types of glaucoma ? |
Primary = congenital can be OAP / CAG Secondary = acquired can be OAG / CAG |
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Reasons for causes of OAG: primary and secondary ? |
Primary = congenital: high IOP or NTG (normal IOP) Secondary = PPP: Pseudoexfoliation syndrome Pigment Dispersion Syndrome Post surgery Use of topical and systemic steroids |
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Reasons for causes of CAG: primary and secondary ? |
Primary: natural history or iris pupil abnormalities or ciliary muscle problems (?) Secondary: uveitis, ret detachment or Amydolosis |
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