Glaucoma Flashcards
What is a common factor of glaucoma?
Acquired progressive nephropathy
What are the risk factors for glaucoma?
High IOP (>21mmHg) Family history Race (Afro-Caribbean) Systemic hypertension CVD Migraine Previous occular disease
What are the types of glaucoma?
Primary
Secondary - occurs due to a secondary disorder
Open angle
Closed angle
Aims of antigaucoma treatment
Reduce IOP <16-20mmHg Sufficient duration of action (less needed) Preserves visual field No loss of effect over time Compatible with other treatments No topical or systemic side effects
Give examples of Prostaglandin analogues
Latanoprost
Travoprost
Tafluoprost
Give an example of a Prostamide analogue
Bimatoprost
Where are prostaglandins produced?
Most cells
Where/how is aqueous humour produced?
Produced in epithelial calls in ciliary muscles
The good blood supply via capillaries brings the fluid
Secreted by epithelial cells and round lens
In open angle - goes between iris and sclemm
At the crook of the angle there is the Trebecular Meshwork - 80% of the fluid flows through
Moves from the anterior to episcleral vein down a pressure gradient
Other route is the Uveoscleral Outflow - goes through cells of schlemm ad ciliary body which has more resistance so moves more slowly
What do the prostaglandin analogues act via?
PGF 2a receptor
A G-coupled receptor = when bound, PLC, DAG and IP3 activates
What is the mechanism of prostamide analogues?
Increase uveoscleral outflow by reducing resistance
Increases matrix metalloproteinases
Degrades collagen and extracellular matirx
Decreases resistance of ciliary muscle and sclera to increase outflow
Most likely via FP receptors and maybe some direct action on tribecular meshwork
What are the side effects of prostaglandin and prostamide analogues?
Red eyes on initial use
Increased pigmentation in iris, eyelashes and periocular skin
Eyelash growth
Precipitate/worsen cystoid macular oedema in aphakic eyes
Sensitivity to light
CI in pregnancy
What are the benefits are of Prostaglandins?
Pro-drugs (ester converted to acid before it can bind)
Long duration of action - OD at night
Efficacy - lower IOP by up to 35%
Good tolerability
How do beta receptors induce aqueous production?
B2 activation stimulates cAMP production (G-coupled so activates adenyl cyclase)
cAMP regulates ion transport in ciliary epithelium
Activates Na+K+2Cl- co-transporter in epithelial cells
Stimulates Cl- efflux in non-pigmentated epithelial cells
Efflux = osmostic gradient increase and increased humour production
What are the advantages of beta blockers?
Well tolerated
Rapid onset
Effective in 75% - lower IOP by 20-30%
Compatible with other drugs
What are the disadvantaged of beta blockers?
Can observe effects on the treated and untreated eye (systemic absorbance)
Systemic SE’s (CVD needs monitoring)
Efficacy declines over time
What are the side effects of beta blockers?
Systemic effects due to beta receptor location
Cardiovascular: hypertension, bradycardia, peripheral vasoconstriction, impotence
Bronchial: constricts bronchioles
Diabetic: Masks hypoglycemia
How do carbonic anhydrase inhibitors work?
Inhibit carbonic anhydrase in ciliary epithelium which catalyses reaction to bicarbonates which are required for aqueous production (secreted into posterior chamber with fluid)
Reduces ion conc
Reduces fluid conc along gradient
Reduces vol of aq humour
Give an example of a systemic CAI and when is it used?
Acetazolamide
Uses: Open angle glaucoma, secondary, peri-operatively in acute angle, when IOP highly elevated
Used in emergencies IV
(Side effects limit use)
What are the side effects of systemic CAI’s?
Increased risk of allergy and blood disorders (sulfonamide derivative)
Many due to enzymes in body:
GIT, Diuresis, Acid-base disturbances, drowsiness/depression, parasthesias
When are topical CAIs used?
With beta blockers or prostaglandin analogues
Alone when beta blockers are not tolerated
What are the side effects of topical CAI’s?
Burning/stinging when used Blurred vision Conjuctival hyperaemia Transient myopathy Blepharitis Allergic conjuctivitis Taste disturbances Dry mouth Headache
Where are the alpha receptors?
ciliary, conjuctival, corneal epithelium cells
What are the effects of alpha adrenoceptor agonists?
No mydriasis
No vasoconstriction
Little effect on CV system as alpha selective
What is the mechanism of alpha adrenoceptor agonists?
Decreased secretion of aq: Reduced cAMP Reduced ion transport Reduced aqueous secretion Reduced ultrafiltration (reduced bood flow and vasoconstriction) Increased uveroscleral outflow
Neuroprotective?
