Ocular Therapeutics

What are the classes of Glaucoma eye drops?

Prostaglandin analogues, beta-blockers, alpha2 agonists, carbonic anhydrase inhibitors, cholinergics

What is the most effective Glaucoma drug class?

PGA's but peak effect is slower than that of beta-blockers (approx. 12 hours compared to 2 hours)

What is the mode of action for PGA's?

Increase uveoscleral outflow of aqueous humour to reduce IOP

What is contraindicated with PGA's?

History of herpetic keratitis, active uveitis, and macula oedema, pregnancy

What are common adverse effects of PGA's?

Iris hyperpigmentation, eyelash growth, and periorbital changes

What are the preservative-free options for PGA's?

Bimantoprost (Lumigan PF & Ganfort PF) and Tafluprost (Saflutan)

Why is having two PGA's normally avoided?

Can cause a paradoxical increase in IOP

Bimatoprost

0.03%, 3mL, Lumigan (PF)

Bimatoprost with Timolol

Bimatoprost 0.03%, Timolol 0.5%, 3mL, Ganfort (PF)

Lantanoprost

0.005%, 2.5mL, Xalatan

Lantanoprost with Timolol

Lantanoprost 0.005%, Timolol 0.5%, 2.5mL, Xalacom

Tafluprost

0.0015%, 0.3mL, Saflutan

Travoprost

0.004%, 2.5mL, Travatan

PGA dosing schedule

1 ggt nocte

What is the mode of action for beta-blockers?

Blocking beta receptors on ciliary epithelium to reduce aqueous humour production

What are contraindications of beta-blockers?

Asthma, bradyarrhythmia, atrioventricular block, uncontrolled heart failure, oral beta blocker, chronic obstructive pulmonary disease

What are the adverse effects of beta-blockers?

Bradycardia, reduced corneal sensation, bronchospasm

What is the comparative information with Beta-blockers?

Timolol is non-selective beta1 and beta2 receptor blocker, whereas betaxolol selectively blocks beta1 receptors. Betaxolol is less likely to cause bronchospasm than timolol, and is less effective at reducing IOP, and is more likely to cause local stinging.

What is the dosing schedule for beta-blockers?

1 ggt bid

Betaxolol

0.5%, 5mL, Betoquin

Timolol

0.5%, 5mL, Timoptol

What is the mode of action for alpha2 agonists?

Supressing production of aqueous humour and increasing uveoscleral outflow to reduce IOP

What are the contraindications for alpha2 agonists?

Central nervous system depression in children, anti-depressants

What are the adverse effects of alpha2 agonists?

May worsen cardiovascular disease, hyperaemia, dry mouth, conjunctival blanching, lid retraction, and follicular conjunctivitis

What is the comparative information for Apha2 agonists?

The effect of Apraclonidine declines over time. Brimonidine is effective long-term, and has lower incidence of ocular allergy.

What is the dosging schedule for alpha2 agonsists?

1 ggt tid

Apraclonidine

0.5%, 5mL, Iopidine

Brimonidine

0.2%, 5mL, Alphagan

Brimonidine with Timolol

Brimonidine 0.2%, Timolol 0.5%, 5mL, Combigan

What is the mode of action for carbonic anhydrase inhibitors?

Inhibit carbonic anhydrase II, which reduces aqueous production

What are adverse effects of CAI's?

Increased risk of corneal oedema, foreign body sensation, dermatitis

What are the contraindications of CAI's?

Sulfonamide allergy, corneal graft

Brinzolamide

1%, 5mL, Azopt

Brinzolamide with Brimonidine

Brinzolamide 1%, Brimonidine 0.2%, 5mL, Simbrinza

Brinzolamide with Timolol

Brinzolamide 1%, Timolol 0.5%, 5mL, Azarga

Dorzolamide

2%, 5mL, Trusopt

Dorzolamide with Timolol

Dorzolamide 2%, Timolol 0.5%, 5mL, Cosdor (PF)

What is the indication for Acetazolamide?

Acute reduction for IOP (e.g. acute angle-closure crisis)

What are the contraindications for Acetazolamide?

Adrenal/respiratory failure, hypomatraonia (electrolyte disturbance), allergy to sulfonamides, and hepatic impairment

What are the adverse effects of Acetazolamide?

Paraesthesia, fatigue, decreased libido, bitter taste, abdominal cramps, renal stones

What is the dosage schedule for Acetazolamide?

Oral/IV 250-500mg, followed by 125-250mg every 4-6 hours

Acetazolamide

250mg, 100, Diamox

What is the mode of action of Mannitol?

Increases plasma osmolality and draws water out of body tissues, producing osmotic diuresis that results in reduced IOP

What is the indication of Mannitol?

Acute angle-closure crisis

What are the contraindications for Mannitol?

Severe heart failure, severe pulmonary oedema, severe dehydration, and renal failure

What are the adverse effects of Mannitol?

Fluid and electrolyte imbalance and tachycardia

What is the dosage schedule of Mannitol?

IV 1-2g/kg (max 100g) 1-1.5h before surgery

What is the mode of action of Pilocarpine?

Cholinergic which contracts; iris sphincter causing miosis (contriction), ciliary muscle (increasing outflow through TM lowering IOP)

What are the indications for Pilocarpine?

Acute angle-closure crisis, chronic open-angle glaucoma, and reversal of mydriatic effect of phynlephrine

What are the contraindications of Pilocarpine?

Acute inflammatory disease of the anterior segment (uveitis)

What are the adverse effects of Pilocarpine?

Myopia, constriction of visual field, lacrimation

What is the dosage schedule of Pilocarpine?

1 ggt tid/qid then increase % (1%, 2%, 4%) slowly according to response

Pilocarpine

2%, 15mL, Isopto Carpine

What are the combination glaucoma eye drops?

Ganfort (Bimatoprost 0.03% + Timolol 0.5%)
Xalacom (Lantanoprost 0.005% + Timolol 0.5%)
Combigan (Brimonidine 0.2% + Timolol 0.5)
Simbrinza (Brinzolamide 1% + Brimonidine 0.2%)
Azarga (Brinzolamide 1% + Timolol 0.5%)
Cosdor (Dorzolamide 2% + Timolol 0.5%)

Why is Chloramphenicol a preferred drug?

Broad spectrum of action, good ocular penetration, is well tolerated, and inexpensive

What are the aminoglycosides and their mode of action?

Framycetin, Gentamicin, and Tobramycin.
They inhibit protein synthesis by binding to the aminoacyl site (30S subunit) of a ribosome.

What is the dosage for aminoglycosides?

1 ggt/2-4 hours for 2 days. Then, if improvement, 1 ggt qid for 5 days. (Framycetin, Tobramycin) Tobrex ointment can be used as adjunct at night.
1ggt/10 min for 1-2h. Then, every h w combo drop hourly on the half hour (Gentamicin)

Why is Gentamicin and Cephalosporin staggered?

For synergistic effect with B-lactam antibiotics (can be inactivated if administered together).

How do the aminoglycosides compare?

Gentamicin and Tobramycin have anti-pseudomonal activity and are generally well tolerated. Framycetin is not active against Pseudomonas species, and is more likely to cause contact allergy.

Framycetin

0.5%, 8mL, Soframycin

Tobramycin

0.3%, 5mL, Tobrex (3.5g ointment can be used as adjunct at night or tid)

Gentamicin

Gentamicin 1.5% (compounded) + cephalosporin 5% (Cephazolin)

What are the Quinolones and their mode of action?

Ciprofloxacin and Ofloxacin.
Inhibit bacterial DNA by blocking gyrase and topoisomerase.

What are the contraindications of Quinolones?

Hypersensitivity and tendon damage, due to risk of recurrence

When is it appropriate to use Quinolones?

Empirical treament of conjunctivitis with contact lens wearers (greater gram -ve coverage, effective against Pseudomonas aeruginosa)

What is the dosage for Ciprofloxacin?

Day 1: 1 ggt/15mins for 6 hours. Then once every 30 mins.
Day 2: 1 ggt/h
Day 3 (till healed): 1 ggt/4h

What is comparative between quinolones?

Ciprofloxacin commonly forms a transient, white precipitate on corneal ulcers that may slow rate of corneal epithelial healing. Ofloxacin has better penetration but can cause corneal perforation.

Ciprofloxacin

0.3%, 5mL, Ciloxan

Ofloxacin

0.3%, 5mL, Ocuflox

What is the dosage for Ofloxacin?

Day 1-2: 1 ggt/30mins (while awake), then at 4 & 6h after bed
Day 3-7: 1ggt/h (awake)
From day 8: 1 ggt qid

What is the mode of action for Chloramphenicol?

Binds to 50S subunit to inhibit bacterial protein synthesis.

What is the dosage for Chloramphenicol?

Conjunctivitis: 1 ggt/2h while awake for 1-2 days. Then, if improvement, 1 ggt qid for up to 5 days. Or ointment qid.
Blepharitis: bid into lid margin bid for 1-3 weeks.
Prophylactic after corneal abrasion: 1 ggt qid until healed.

What is Chloramphenicol bacteriostatic activity against?

Broad spectrum against gram-positive, gram-negative (except pseudomonas spp. with contact lens wearers) and anaerobic bacteria. Good ocular penetration

Chloramphenicol

0.5%, 10mL, Chlorsig (drops)
1%, 4g, Chlorsig (ointment)

What is the mode of action of antivirals?

Inhibits viral DNA synthesis by acting as a competitive substrate.

What is the dosage for Aciclovir?

1 cm of ointment into lower conjunctival sac 5x/day for 14 days, or for 3 days after corneal epithelium healed.

Aciclovir

3%, 4.5g, ViruPOS

What should be done before starting treatment for allergic conjunctivitis?

Identify and avoid triggers (e.g. pollen, animals, dust mites)

What is a non-therapeutic treatment for allergic conjunctivitis?

Cold compress

Why use topical antihistamines?

More rapid onset compared to oral antihistamines (particularly for isolated ocular symptoms).

Which antihistamines have mast cell stabilising properties?

Azelastine, ketotifen, and olopatadine.

Why are mast cell stabilisers not useful for acute symptoms?

Can take up to 2 weeks to reach full effect. However, they can be started 2-4 weeks before hayfever season or if used with topical antihistamine for initial symptom control.

What should be considered when the response to other treatments is inadequate and additional anti-inflammatory effects are needed for seasonal allergic conjunctivitis?

Ketorolac NSAID, but can cause ocular irritation.

Why are vasoconstrictors not recommended?

Their benefit is doubtful, and rebound hyperaemia can lead to overuse. They should be used in combination with antihistamines.

What are the precautions for vasoconstrictors?

May precipitate acute angle-closure crisis.

What is the mode of action of antihistamines?

Bind to the H1 receptor and stabilise it in an inactive form to reduce the effects of histamine.

What are the antihistamines?

Antazoline, Levocabastine, Pheniramine
(Antihistamine-mast cell stabilisers: Azelastine, Ketotifen, Olopatadine)

What is only available in combination with naphazoline?

Antazoline and pheniramine

Nephazoline with anatazoline

nephazoline 0.05%, antazoline 0.5%, 15 mL, Albalon-A

Nephazoline with pheniramine

naphazoline 0.025%, pheniramine 0.3%, 15 mL, Naphacon-A

What is the dosage of antihistamines?

1 ggt bid, increase to 1 ggt qid if needed.

What is the dosage of antihistamine vasoconstrictor combination?

1 ggt/6-12h as required.

Azelastine

0.05%, 6 mL, Eyezep

Ketotifen

0.025%, 5 mL, Zaditen

Levocabastine

0.05%, 4 mL, Livostin (Zyrtec Levocabastine)

What is an adverse effect of Levocabastine?

Drowsiness, may increase effect of alcohol

Olopatadine

0.1%, 5mL, Patanol

What are the mast cell stabilisers and their mode of action?

Cromoglycate and Lodoxamide.
Inhibit release of inflammatory mediators from mast cells.

What are counselling points for mast cell stabilisers?

Delayed onset of action of at least 2 weeks (start before hay fever season). Combination with antihistamines are generally preferred as it can provide rapid sympotom relief.

What is the dosage of mast cell stabilisers?

1 ggt qid