Glaucoma A Flashcards
Ciliary body & aqueous humor inflow: Key tissues & mechanisms
Step 1: Ciliary processes & ultra-filtration
Step 2: Ion transport & osmotic gradient-driven H2O movement↓ag. production, Key role of nonpigmented ciliary epithelium
5 beta blocker options
Timolol - nonselective
Betaxolol - beta1-selective
Levobunolol - nonselective, active metabolite
Metipranolol - nonselective
Carteolol - nonselective, Intrinsic sympathomimetic activity
Available topical ophthalmic Beta-blockers: Differences in profiles
- Selectivity
>nonselective (NonS)
>b1 selective (cardioselective) - intrinsic sympathomimetic activity (ISA)
- membrane stabilizing activity (MSA)
Beta adrenergic blocking agents (Beta-blockers): Mechanism of action
- decreased aqueous inflow
>decrease Cl- transport (b2 receptors) - effect mostly on daytime flow (decreased sympathetic tone at night)
Beta-blockers: Special identifying properties
-no control at night
* neuroprotection (betaxolol>metipranolol>timolol)
>calcium channel blocking action + less vas effect (betaxolol)
>MSA activity?
* contralateral (cross-over) effect with timolol
>monocular efficacy trials un-interpretable
* levobunolol long acting (active metabolite)
* incr. efficacy levobunolol with chronic therapy
* tachyphylaxis & tolerance (escapes/drifts)?
* Black people may show smaller IOP decreases (pigment binding + receptor polymorphism?)
beta-blockers: Ocular side-effects
- stinging - betaxolol (less c suspension)
- punctate keratitis & dry eye
-preservative (BAK) contribution
-timolol available with benzododecinium Br or NP (Ocudose)
-not see with levobunolol? - decr. corneal sensitivity (MSA)
-timolol
-carteolol greatest effect - allergies (rare)
-timolol
-levobunolol - uveitis (rare)
- decrease in ONH perfusion?
-incr. risk pseudophakics, aphakics
-betaxolol not problematic
Potential systemic side-effects: Predictions based on distribution of adrenergic receptors
- α1 receptors - blood vessels (VC)
- α2 receptors - presynaptic nerve terminals (decr. NE release)
- β1 receptors - heart
- β2 receptors - respiratory system, blood vessels (VD), glycolysis
- β3 receptors - adipose tissue
Topical b-blockers: Systemic side-effects
- nonselective drugs most problematic
- respiratory distress (b2) (least with betaxolol)
- cardiovascular (hypotension, CHF, b1/2)
- diarrhea
- skin rashes
- altered plasma lipids (decr HDL, incr TGs, b3)
- hypoglycemia masked (b2)
- reduced significantly by NLO
- less side-effects with carteolol & betaxolol (inactive metabolite+protein binding)
CNS effects
* light headedness
* amnesia
* depression
* fatigue
* dissociative behavior
beta-blockers: contraindications & drug interactions
contraindications
* bronchial asthma (except betaxolol??)
* labile diabetics (masking of hypoglycemia)
* thyroid disease (masking of symptoms)
* cardiovascular disease?
drug interactions
* systemic beta-blockers - reduced potential for lowering IOP
* calcium channel blockers?
* heart medications (include. cardiac glycosides)
* beta-agonists
* NSAIDs
Alpha2 agonists: 2 options
aproclonidine (Iopidine) - slight selectivity (a2>a1)
brimonidine (alphagan) - selective (a2>a1), more lipid soluble & high melanin binding
alpha 2 agonist mechanism of action
- decrease aqueous production
- indirect effects via
-decr. cAMP in ciliary epithelium
-altered vascular tone (VC) in ciliary body?
-altered PG synthesis - also improvement BAB (decrease aqueous flare post-op)
- late increase uveoscleral outflow (brimonidine)
- neuroprotective (brimonidine)
Alpha2 agonists: Indications for use
- open angle glaucoma (brimonidine)
- extreme tachyphylaxis with aproclonidine (30 50%) & other side-effects limit therapeutic use to short term:
- initial treatment in AACG
- controls IOP spikes
* post-operatively (ant. segment laser; also controls bleeding)
* post-dilation/cycloplegia - short term control prior to filtering surgery
* adjunct to “max therapy”
Alpha2 agonists: Ocular side-effects
- greater with aproclonidine (greater a1 activity)
- conjunctival blanching (a1, no rebound?)
- eyelid retraction (a1, monocular treatment issue)
- pupil mydriasis with aproclonidine (a1, usually slight), miosis for brimonidine (a2)
- ocular irritation/burning/itching/dryness
- allergic reaction (with longer term therapy; 20-50%, aproclonidine)
- periorbital dermatitis (less with brimonidine purite formulations)
Alpha2 agonists: Systemic side-effects & contraindications
Side-effects
* dry mouth/nose & taste abnormality (VC effect, greater with aproclonidine)
* minimal cardiovascular side-effects (decr. BP?)
* slight respiratory distress
* CNS
* fatigue/lethargy/confusion
* headaches
Contraindications & interactions
* very young & very elderly (CNS effects)
* MAO inhibitors (hypertensive crisis risk)
* TCAs (increased risk CNS depression)
* enhances anti-hypertensive, sedative effects?(brimonidine)
CNS penetration greater for brimonidine, esp in young children < 6yo
Carbonic anhydrase inhibitors (CAIs): 4 options
All are sulfa drugs
Topical
* dorzolamide
* brinzolamide
Oral/Intravenous
* acetazolamide
* methazolamide
