2 - Anti-glaucoma drugs Flashcards
AH production how
- Carbonic acid makes HCO3- and H+, which is antiported w/ Cl- and Na+ respectively. Cl- and Na+ move to NPE where they’re excreted to posterior chamber. H2O flows due to osmotic gradient generated.
- 3Na+/2K+ ATPase + K+ leak channel increases Na+ and K+ concentration gradient outside PE. Then 2Cl-/Na+/K+ symporter allows Cl- into PE where it goes to NPE for excretion…
3 theories of how IOP causes glaucoma
- Mechanical: Fenestrations of lamina cribrosa are impeded which damage ONH fibres which cause GC death
- Vascular: Pressures block off BVs which damage ONH fibres causing GC death
- Neurochemical: Increased glutatmate is toxic and causes GC death.
How does NT glaucoma cause damage?
Theory: More sensitive tissue = damage at normal IOP ranges.
Direct acting cholinergic agonists
- Mechanism
- Name 2 drugs
– Concentration
– Use case
- Stimulate mACh receptors – Longitudinal part of ciliary muscle contracts –> pulls scleral spur to open TM up
- Contracting sphincter pupillae opens angle via miosis.
- Outflow at TM increased.
Pilocarpine:
- 1-6%
- Both angle types of glaucoma
- 4x daily (qds)
- Best for <40mmHg closed angle (when >40mmHg, already ischaemia so not as effective)
Carbachol:
- Also nAChR (nicotinic)
- Causes ACh release
- Prolonged action (not hydrolysed by acetylcholine esterase)
- Main use for surgery.
Direct acting cholinergic agonist
- Side effects
- Contraindication
Side effects:
Ocular:
- Accom spasm –> browache
- RD (if high myope)
Systemic (uncommon):
- Headache
- Salivation
- Sweating
- GI distrubance
Contraindication:
Ocular:
- Myope high/previous RD
- Cataracts
- Young Px (intolerable to accom spasm/Rx change)
Systemic:
- Asthmatics
- Ulcers
- Bladder dysfunction
- Parkinsons’
- Cholinergic agonist use
How do adrenergic receptor drugs work?
Beta stimulation -> ATP activation -> cAMP -> Kinase A -> effect
- HR + heart pump force
- Bronchodilation
- Vasodilation
Alpha stimulation -> less adenylcyclase -> less effect
- Pupil dilation
- Saliva
- Vasoconstriction
Epinephrine
- Concentration
- Mechanism
- Effect on IOP
- 1 or 2%
- Stimulates Alpha + Beta1 + some beta 2
- Mydriasis
- Decrease aqueous production (due to vasoconstrict)
- Outflow also increased via c-AMP synthesis due to b2
- 20 – 25% IOP drop
Dipivefrin
- Concentration
- Mechanism
- Effect
- 0.1%
- Epinephrine prodrug
Relative to epinephrine: - More lipophilic, more penetration
- Less local + systemic side effects
- Lower aqeuous produced
- More outflow via TM AND uveoscleral
- Often combine w/ beta blockers.
Alpha + beta agonist:
- Side effects
- Contraindications
Side effects:
Ocular:
- Irritation (avoid if allergic)
- Pigmentation of Lid and Cornea
Systemic:
- Headache
Contraindications:
Ocular:
- Narrow angles
- Aphakia
- Pseduoaphakia
Systemic:
- MAOI
- TCA
- CV disease
- HS to adrenaline
Always know what they’re on before prescribing to Px
Apraclonidine
- Concentration
- Mechanism
- BBB?
- 0.5%
- Selective a2 agonist (lower cAMP -> less AP)
- Decreased AP
- Increased uveoscleral outflow
- Less likely crosses BBB
Brimonidine
- Concentration
- Mechanism
- BBB?
- 0.2%
- Very selective a2 agonist
- Potent
- Decreases AP
- Increased uveoscleral outflow
- Crosses BBB (neuroprotection)
Alpha2 agonist:
- Side effects
- Contraindications
Side effects:
Ocular:
- Irritation, burning, itching (avoid w/ allergy Px)
- Lid retraction (dry eye worsens)
Systemic:
- Headache
Contraindications:
Systemic:
- MAOI
- TCA
- CV disease
Beta blockers
- Mechanism
- Effect on IOP
- Different drug types.
- Beta receptors normally enhance ATP to cAMP via adenylate cyclase to increase AH flow
- Drop IOP by 20-25%
- Non-selective = Timolol
- Beta1 selective = Betaxolol
- Non-selective = Levobunolol
Beta blockers:
- Side effects
- Contraindications
Side effects:
Ocular:
- Stinging
- Burning
- Dry eye
Systemic:
- Impotence
- Bradycardia (Slow HR)
- Depression
Contraindication:
- Narrow angles
- COPD (or any breathing issues, want to avoid due to lower HR)
- Bradycardia
use betaxolol to reduce risk in asthmatics although less IOP effectiveness.
CAI
- Mechanism
- Types of drugs
- Side effects
- Contraindications
Carbonic Anhydrase Inhibitors prevent HCO3- formation from H2CO3. Reduces Cl- formation, thus less H2O movement.
- Dorzolamide 2%
- Brinzolamide 1%
- Acetazolamide 250mg
- Dorzolamide 2%
- Brinzolamide 1%
- Acetazolamide 250mg
Dorzolamide + Brinzolamide:
- Headaches
Acetazolamide:
- GI distress
- Depression
Contraindications:
- Hepatic problems (avoid systemic drugs generally)
