CA Inhibitors

Question 1

What is glaucoma? What is it caused by?

Answer 1

a group of eye disease which result in damage to the optic nerve and cause vision loss

is caused by a build up of aqueous humour (fluid) in the eye which increases intraocular pressure

Question 2

What causes an increase in aqueous humour?

Answer 2

increased aqueous humour formation or decreased outflow

• occurs due to increased bicarbonate concentration which as a result increases aqueous humour production via osmosis

Question 3

How can carbonic anhydrase inhibitors treat glaucoma?

Answer 3

carbonic anhydrase inhibitors treat glaucoma by inhibiting the production of bicarbonate
- CA hydrolysis of carbon dioxide/water leads to bicarbonate production

Question 4

How do carbonic anhydrase inhibitors act on carbonic anhydrase?

Answer 4

can bind to CA in two ways
- substitution reaction
= replaces the water molecule with itself

• addition reaction
  = adds itself to the CA complex

Question 5

What are the class of CA inhibitors called? How do they act?

Answer 5

sulphonamides

- amide on the sulphur forms a dative bond with the zinc centre in CA

Question 6

Why do sulphonamides cause side effects?

Answer 6

are not specific to CA isozymes in the eye but also inhibit CA isozymes in other tissues

Question 7

What are the common side effects of CAIs?

Answer 7

numbness and tingling of extremities
metallic taste
depression
fatigue
malaise
weight loss
decreased libido
GI irritation
acidosis
kidney stones

Question 8

What are the side effects of Acetazolamide?

Answer 8

is given orally
- can have a metallic taste

wide range systemic effects due to oral usage

• fatigue
• numbness and tingling of extremities
• kidney stone

Question 9

What are the side effects of Brinzolamide?

Answer 9

structural modifications were needed to make it topically active
- modification to ring system to which sulphonamide was attached

tinging, burning or reddening of the eye
- is water soluble but is also acidic (pH = 5.5)

Question 10

What are the side effects of Dorzolamide?

Answer 10

structural modifications were needed to make it topically active
- modification to ring system to which sulphonamide was attached

blurred vision
- less water soluble so can penetrate through cornea (phosphplipid bilayer) - hence formulated as suspension but causes blurred vision due to formulation

Question 11

What are examples of CAIs?

Answer 11

acetazolamide
dorzolamide
brinzolamide - most effective

Question 12

What are the desired properties of CAIs?

Answer 12

topical
- reach site of action

water soluble
- to be given as a solution not a suspension

sufficiently lipophilic
- to cross the cornea (phospholipid bilayer)

high activity
- reduces dose

low cost
- no chiral centres = no need for separation

few side effects

moderate pka
- reduces stinging
= larger pka means its less acidic