11.2 - Glaucoma, Glaucoma Drugs

Front 1

(a) What is glaucoma?

Back 1

Increased IOP --> optic nerve damage --> progressive visual field loss

Front 2

(a) How is IOP reduced pharmacologically and surgically?

Back 2

1. reduce production of aqueous humour
2. increase outflow of aqueous humour
3. peripheral laser iridotomy

Front 3

How is aqueous humour made?
How is aqueous humour lost?

Back 3

1. AH made by ultrafiltration of blood vessels at ciliary body in the posterior chamber
2. Passes between lens and iris into anterior chamber, and passes out through filtration angle between iris and cornea and then diffuses into the TREBCULAR MESHWORK (CT) through the CANAL OF SCHLEMM in the sclera
*Also, some AH diffuses out via UVEOSCLERAL PATHWAY (4-18%)

Front 4

What is normal IOP?

Back 4

10-21mmHg, average about 15mmHg

Front 5

Open angle glaucoma
- risk factors?
- early signs?

Back 5

Risk factors
- age, family Hx
Early signs
- frequent lens changes
- mild headache
- halos around lights
- impaired dark adaptation

Front 6

Closed angle glaucoma
- what is the closed angle?
- what is the IOP?
- we covered S+S under Red Eye so you don't have to repeat here: remember: mydrisasis vs. miosis (uveitis)

Back 6

- closed angle between the cornea and the iris
- IOP is ~50mmHg

Front 7

What are secondary causes of glaucoma?

Back 7

- trauma
- inflammation
- tumours
- cataracts
- PROLONGED CORTICOSTEROID DROPS

Front 8

(a) What is one barrier to treatment of chronic open angle glaucoma (OAG)?
(b) what is the target IOP?

Back 8

(a) compliance is equal to or greater than 50%
(b) it depends on each patient and is set by the specialist - e.g. extent of retinal damage, site of damage, family history

Front 9

Holding tear ducts closed - how long and what effect?

Another important counselling point for these drops?

Back 9

1. 3mins
2. up to 70% reduction in systemic absorption

Seperate drops by at least 5 minutes

Front 10

OAG - what are the treatments and which are used first, second, third?

** Consider this question as in the context of a potential exam question

Back 10

1. Prostaglandin analogues (bimatoprost, latanoprost, and travaprost)
2. Beta-blockers (betaxolol, levobunolol, timolol)
THEN
2. Alpha2 agonist (brimonidine, apraclonidine)
3. Topical carbonic anhydrase inhibitor (brinzolamide, dorzolamide)
3. Cholinergic (Pilocarpine)
4. Nonselective adrenergic agonist (Dipivefrine)

Also acetazolamide (as effective as BB and prostaglandins), mannitol used more frequently for CAG

**When getting to last line, consider: (1) compliance, (2) holding tear duct closed, (3) trying different prostaglandins
** Or surgery: trabeculectomy or insertion on a mini shunt

Front 11

OAG - which are
(A) most effective
(b) least effective
(c) least dosed
(d) most dosed

Back 11

Front 12

Prostaglandin analogues
- drugs in class
- mode of action
- comparative efficacy

Back 12

1. Bimatoprost, Travaprost, Latanoprost
2. Analogues of PG-F2alpha
Increase uveoscleral outflow of AH
3. Evidence of increased efficacy cf Beta blockers

Front 13

Prostaglandin analogues
- CIs, cautions
- Pregnancy
- BF
- LF and RF are okay

Back 13

- CI: active introcular inflammation, such as uveitis; caution if there is a history of this
- Latanoprost increases recurrence of ocular herpes simplex
- B3: no data, avoid
- BF: no data, but unlikely to be a concern - LATANOPROST is safe to use

Front 14

Prostaglandin analogues
- Adverse effects

Back 14

Common
- gradual usually irreversible darkening of iris, especially if mixed colored eye (concern if only one eye is treated)
- lengthening and thickening of eye lashes
- transient conjunctival hyperaemial
- latanoprost causes ocular irritation and bitter taste due to preservative; the others can cause itch

Front 15

Prostaglandin analogues
- are they equally effective?
- can two be used together
- specific counselling points (2)

Back 15

- yes, but they are structurally different so if response to one is poor, consider trying another
- No! may cause paradoxical increase in IOP
- (1) use at night for increased effect (2) may change eye color gradually, and is more noticeable if only one eye is treated

Front 16

Latanoprost
- products, combo products

Back 16

Xalatan - 0.005%, 2.5mL
Xalacom - 0.005%/0.5%, 2.5mL with Timolol

Front 17

Bimatoprost
- product

Back 17

Lumigan - 0.03%, 3mL

Front 18

Travaprost
- products

Back 18

Travatan - 0.004%, 2.5mL
DuoTrav - 0.004%/0.5%, 2.5mL with timolol

Front 19

Dosage of prostaglandin analogues alone and in combination?

Back 19

Alone: 1 drop daily, preferably at night

With timolol: 1 drop daily, preferably at night

Front 20

Beta-blocker eye drops
- drugs in class
- mode of action

Back 20

- levobunolol, betaxolol, timolol
- Reduce production of AH by 1/3 by blockade of beta-2 receptors on ciliary body epithelium
- NB: there is no B1 receptors in the eye
- NB: betaxolol is B1 selective when NOT used in the eye.
- The other BBs are not selective

Front 21

Beta-blocker eye drops
- CI/cautions
- Preg
- BF
- N.B. ok in liver and renal disease

Back 21

1. CI in asthma but B1 selective betaxolol may be used with care
2. Caution in CVD
3. Avoid combination with systemic BB (increased risk of sytemic A/Es and decreased result as systemic BB already reduces IOP somewhat)
4. Avoid use with verapamil
- Also use with caution in children, the elderly and in surgery
- Pregnancy: C: fetal bradycardia occurs
- BF: unlikely to cause A/Es

Front 22

BB eye drops
- A/Es

Back 22

Common:
- stinging on instillation (especially betaxolol SOLUTION)
- bradycardia

Infrequent
- hypotension, fatigue, syncope, hallucinations, bronchospasm

*NB: betaxolol suspension is as effective as the solution by has less stinging

Front 23

BB eye drops
- which is more effective?
- how long do they work for?
- how long do they work after they are stopped?

Back 23

- Betaxolol is slightly less effective than the others and has more stinging, but is less likely to cause bronchospasm
- There may be a slight decrease in effect in the first month, and then tolerance may develop after 1 year
- after stopping, returns to baseline in 2-4 weeks

Front 24

Betaxolol
- products

Back 24

0.25%.5mL suspension (Betoptic-S)
0.5%.5mL solution (Betoptic, Betoquin)

Front 25

Levobunolol
- products

Back 25

0.25%.5mL (Betagan)

Front 26

Timolol
- products

Back 26

0.25%.5mL solution (Tenopt, Timoptol)
0.25%.2.5mL SR solution (Timoptol-XE)

0.5%.5mL solution (Tenopt, Timoptol)
0.5%.2.5mL SR solution (Timoptol- XE)

0.1%.5g eye gel (Nyogel)

0.5%/0.005%.2.5mL (Xalacom - with latanoprost)
0.5%/0.004%.2.5mL (DuoTrav - with travaprost)
0.5%/2%.5mL (Cosopt - with dorzolamide)
0.5%/0.2%.5mL (Combigan - with brimonidine)

Front 27

Dosing of BB eye drops

Back 27

Betaxolol (Betoptic) and Levobunolol (Betagan): 1 bd

Timolol solution: 1 d-bd (0.25-0.5%)
Timolol XE solution: 1 d (0.25-0.5%)
Timolol gel: 1 DROP d

Xalatan, DuoTrav: 1 n.
Combigan, Cosopt: 1 bd.

Front 28

Alpha-2 agonist eye drops
- drugs in class
- mode of action

Back 28

- apraclonidine and brimonidine
- Reduces production of AH, and increases uveoscleral outflow of AH

Front 29

Alpha-2 agonists eye drops
-A/Es

Back 29

Common
- occular irritation
- dry mouth and nose
- taste disturbance
- Apraclonidine has high incidence of allergic reactions after 3/12 use
- Brimonidine: fatigue, dizziness

Infrequent
- palpitations, reduced BP

Front 30

Is apraclonidine better than brimonidine?
When is apraclonidine used?
Specific counselling point for brimonidine?

Back 30

- slightly better (5% increased IOP reduction) HOWEVER apraclonidine is only for short term use (3/12) as its effect declines after a month
- Apraclonidine may be used before surgery for CAG and last line, short use addition to OAG
- Label 1 & 16

Front 31

Apraclonidine - products

Back 31

0.5%.5 and 10mL (Iopidine)

Front 32

Brimonidine - products including combo

Back 32

Alphagan, Enidin
0.2%.5mL

Combigan - 0.5/0.2%

Front 33

Dosing of alpha-2 agonists

Back 33

1 bd-tds

Combigan: bd

Front 34

Carbonic anhydrase inhibitors (CAIs)
- drugs in class (topical)
- MOA

Back 34

- brinzolamide, dorzolamide, acetazolamide
- inhibits CA II, which reduces product of AH

Front 35

CAIs
- CIs
- Preg
- BF

Back 35

- Allergy to sulphonamides!!!! - increased risk of allergy to CAI
- Preg B3 - no data
- BF: no data

Front 36

CAIs
- A/Es

Back 36

Common
- irritation
- foreign body sensation
- bitter taste

Infrequent: blepharitis, corneal staining

Rare: allergy

Front 37

CAI
- place in therapy?
- specific counselling point

Back 37

- after or with BBs
- You may initially experience eye discomfort or blurred vision

Front 38

Brinzolamide - products

Back 38

1%.5mL (Azopt, BrinzoQuin)

Front 39

Dorzolamide
- products

Back 39

2%.5mL (Trusopt)
2%/0.5%.5mL (Cosopt - with timolol)

Front 40

CAI
- dosing

Back 40

Trusopt: 1 tds
Cosopt: 1 bd
Azopt: 1 bd

Front 41

Acetazolamide
- products
- indications
- contraindications

Back 41

- 250mg.100 tabs (Diamox), and also IV on SAS
- CAG, last line OAG, epilepsy in particular absense seizures
- CI: metabolic acidosis, renal, adrenal, respiratory or hepatic failure
- Sulphur allergy
- May worsen gout, kidney stones

Front 42

Diamox
- side effecst
- counselling point

Back 42

- up to 50% do not tolerate Diamox
- tingling, fatigue, depression, decreased libido, taste disturbance, n/v/abdo cramps, black faeces, kidney stones, acidosis, electrolyte disturbance

INFREQUENT: SJS

Take with food to reduce stomach upset

Front 43

Dipivefrine
- MOA
- products

Back 43

- Pro-drug of adrenaline. Alpha agonist: increases uveoscleral outflow. Beta agonist: decreases aqueous inflow
- Propine 0.1%.10mL

Front 44

Propine
- A/Es

Back 44

Common
- irritation
- Allergy with long term use
- rebound hyperaemia 2hr after use
- pigmentation of conjunctiva (long term)
- mydriasis
- frontal headach

Rare: palpitations, anxiety, HTN, increased HR

Front 45

Propine
- dose
- place in therapy
- use with BBs

Back 45

1 bd

Limited use due to low efficacy and frequent occular A/Es

Limited additional effect when used with pilocarpine, dorzolamide or betaxolol

Use at least 5 mins before BBs

Front 46

Pilocarpine
- MOA

Back 46

- Cholinergic: contracts iris and ciliary muscle (miotic), causing increased outflow through trabecular meshwork

Front 47

Pilocarpine
- products

Back 47

0.5%, 1%, 2%, 3%, 4%, 6% (Pilopt, Isopto Carpine, P.V. Carpine)

1%, 2%, 4% x20 single use drops (Minims Pilocarpine Nitrate)

Front 48

Pilopt
- A/Es

Back 48

Common (Dose dependent):
- miosis, blurred vision & frontal headache (usually decreases after 2-4 weeks)
- occular irritation

Miosis is potentially permanent with long term use, and may worsen vision: reassess visual acuity for driving.

Front 49

Isopto Carpine
- indications
- Preg/Bf

Back 49

- OAG, pre-surgery CAG, reversal of weak mydriatics (not recommended)
- CI: uveitis (like prostaglandin analogues), secondary glaucoma due to outflow obstruction (may worsen)
- Be: ltd data
- BF: safe to use

Front 50

Pilopt
- dosing

Back 50

Start on 0.5-1% 1 tds-qid
Usual: 2% qid
Maximum: 4% qid with light iris, 6% qid with dark iris

(Perhaps darkness is related to thickness of iris sphincter)

To reverse mydriasis: 1% drop
For OAG: 4% every 5min until miosis