Drugs in Glaucoma

Question 1

what is glaucoma?

Answer 1

blanket term for a variety of conditions

• differenet features
• different mechanisms
• not just one typical disease affects everyone who suffers

the common factory is acquired progessive neuropathy if left untreared

• optic nerve damage
• visual field loss
• eventual blindness

Question 2

what are the risk factors of glaucoma/

Answer 2

• normally asymptomatic, no warning signs
• high IOP >21mmHg (normal is 12-16)
• family history
• afro caribbean are more at risk
• systemic hypertension
• migraines
• previous ocular disease or surgery
• usually due to impaired drainage of the aqueous humour

Question 3

where is aqueous humour produced?

Answer 3

cilliary muscle is the outer most part of the epithelial cells and has a large blood supply which makes up the aqueous humour.
it goes round the lens and into the side.
meshwork of cells means there are spaces for the aqueous humour to flow

Question 4

what do we look for in antiglaucoma treatment?

Answer 4

• reduction in occular pressure <16-20mmHg depending on patient
• anything under 21 should reduce risk of neuropathy
• drug needs to have sufficient duration of action to increase patient compliance
• compatability with other treatments
• no side effects
• no loss of vision over time
• keeps vision as best as it can be

Question 5

what are the first line treamtents for glaucoma?

Answer 5

prostaglandin f2 alpha

prostamide f2 alpha

Question 6

what is prostagladin E/

Answer 6

this controls the production of aqueous humour, but it is very unstable and breaks down rapidly

Question 7

what is prostglandin f2 alpha?

Answer 7

abit more stable, so this is what they design drugs on
- analogues are all esters whereas it is an acid. this increases stability of the drug and gives it a longer duration of action on the eye

Question 8

what are prostagladins used for in the eye?

Answer 8

they are produced naturally in most cells not just within the eyes
involved wirh
- aquous humour outflow
- first choice clinically
- unique mechansim of decreasing IOP

Question 9

how do prostagladin analogues work?

Answer 9

they act via the PGF2a receptor - they need to be converted back to the acid form from the ester form.
the analoguse are the pro-drug
they are g-coupled receptors

Question 10

what are examples of prostaglandin analogues?

Answer 10

latanoprost, tafluprost and travoprost

• all pro drugs
• long duration of action
• greatest efficacy of the drugs available
• lowers IOP by 35%
• not too many side effects

Question 11

what are prostamide analogues?

Answer 11

• increase uveoscleral and trabecular outflow
• not a pro drug
• effiacy, tolerability and side effects are the same as prostaglandin

Question 12

what are the side effects of prostaglandin?

Answer 12

• red eye of initial use
• increase pigmentation in iris and eyelashes
• can increase eyelash growth, but sometimes you only do it to one eye
• sensitivity to light
• contraindicated in pregnancy

Question 13

what is the second line treatment of glaucoma?

Answer 13

beta receptor induced aqueous production

Question 14

how do beta receptors work?

Answer 14

b2 activation stimulates cAMp production, this causes an increase in ion transport across the cell
when there is an efflux of ions into the posterior chamber, it increase osmotic gradient and more fluid is filtered so increase in aqeuous humoiur
BETA BLOCKERS PREVENT THIS and decrease the production

Question 15

what is the mechanism of action of beta blockers?

Answer 15

• Decreased ion concentration
• Decreased fluid along osmotic gradient
• Decreased volume of aqueous humour
• Better balance of production and drainage
Different angle to treat glaucoma – prevent the amount of aqueous humour to be produced so there is less to be drained out

Question 16

what are the advantages of beta blockers/

Answer 16

• well tolerated
• rapid onset
• effective in 75% of patients, lower IOP 20-30%

Question 17

what are the disadvantages of beta blockers?

Answer 17

• can observe effects on treated and untreated eye - systemic absorption
• CVD patients have problems
• efficacy declines over time
• twice daily - poorer patient compliance

Question 18

what are the side effects of beta blockers

Answer 18

• generally systemic
• cardiovascular, bradycardia, hypotension
• contraindicated in heart block
• diabetic
• constricts bronchiolea

Question 19

what are the fixed dose combinations?

Answer 19

Different classes of drugs have additive effects – as they have different mechanisms. If you put a prostaglandin and a beta blocker together you might not get a decrease of 65% but it will be higher then one by itself

Question 20

what are the advantages of a fixed dose combination?

Answer 20

• better patient compliance
• reduced exposure to preservatives
• avoids washout effects
• decreased cost of treatment
• decreased cost to patient

Question 21

what are carbonic anhydrase inhibitors?

Answer 21

third line treatment
The only time you would use a carbonic anhydrase is if the other two drops were not suitable for some reason.
ONLY USED FOR EMERGENCIES

Question 22

how do carbonic anhydrases inhibitors work?

Answer 22

 This enzyme catalyses the following reaction
 CO2 + H2O  H2CO3  H+ + HCO3-
 The bicarbonate ions tend to be excreted out into posterior chamber and when this happens you get fluid following these ions
 This means if we can stop the bicarbonate ions from forming we can reduce aqueous humour production

Question 23

what is an example of a CAi?

Answer 23

Acetazolamide

• not absorbed topically
• not particularly lipophilic
• short term use only

Question 24

what are the side effects of Acetazolamide?

Answer 24

 Increased risk of allergy and blood disorders because is has sulphonamide group attached
 Enzyme present throughout body -kidney blood and lungs also within the CNS
 Gastrointestinal problems –Diuresis
 Acid / base balance disturbances
 Drowsiness, depression
 Parasthesias

Question 25

when would you use topical cais?

Answer 25

 Adjunct treatment with beta blockers or prostaglandin inhibitors – additive mechanism rather then being used by themselves
 Indicated as sole therapy when patient cannot use beta blockers
 Produce an approximate reduction of 20% - less officious

Question 26

when would you use alpha adrenoreceptor agonist?

Answer 26

 a receptor selective
 Receptors are on the ciliary epithelial cells, conjunctival and corneal epithelial cells
 Advantages
 Very few side effects
 No mydriasis
 No vasoconstriction
 Little effect on the cardiovascular system

Question 27

what is the mechanims of alpha adrenoreceptor agonist?

Answer 27

 Similar mechanism to the beta blockers
 Decrease secretion of aqueous
 Decreases cAMP (Gi coupled; inactivates adenylate cyclase), when you use an agonist they will decrease cAMP
 Decreases ion transport and efflux of ions
 Decreases aqueous secretion due to an decrease in osmotic gradient
 Decreases ultrafiltration – less fluid being filtered through from capillaries
 (reduced blood flow, vasoconstriction)
 Increases uveo-scleral outflow – mechanism is unknown for this?
 Neuroprotective?
 Optic nerve, retinal ganglion cells

Question 28

what are parasympathomimetics?

Answer 28

 Mechanism
 Contract ciliary muscle
 Pulls scleral spur – this is the bit that goes into the eye
 Opens trabecular meshwork – damaged in some way but now the fact it is stretched out more there is more drainage being able to occur
 Increases trabecular outflow
 Decreases IOP