lec 10: ocular hypotensive agents (carbonic anhydrase inhibitors)

CAIs

what are the four CAIs

acetazolamide (diamox)

methaxolamide (neptazane)

dorzolamide (trusopt)

brinzolamide (azpot)

what color caps are CAIs

orange caps

what is essential for aqueous production

bicarbonate formation

where is carbonic anhydrase found

ciliary processes

what does carbonic anhydrase do

It catalyzes the conversion of carbon dioxide and water into carbonic acid, facilitating bicarbonate formation

without bicarbonate you dont have aqueous humor production

how does the use of CAIs work

it inhibits bicarbonate formation which also acts on decreasing sodium entry into posterior chamber by decreasing fluid movement across the nonpigmented ciliary epithelium

which decreases bicarbonate, sodium, and water moving from ciliary processes into post. chamber which leads to a net result of decrease aqueous production and decrease in IOP

the formation of bicarbonate does what

allows sodium to get from stroma into aqueous

and water follows 

what is metabolic acidosis

if you use a CAI that will decrease bicarbonate ions which will not cancel out the hydrogen ions that are in the blood

what happens with an increase in CO2

increase in CO2 → increase in hydrogen ions in the blood → deep respiration (people trynnna get CO2 outta their body)

where is CA a function of 

the corneal endothelium 

job: pump fluid outta the cornea (keep it outta the stroma)

how does carbonic anyhdrase work with the corneal endothelium

any water that accumulates in the stroma gets pumped back into the aqueous chamber so that the cornea is normally hydrated not too much with corneal edema

CAIs case…

metabolic acidosis

and can cause worsening of corneal edema (fuch’s endothelial dystrophy)

^ esp the oral CAIs

aceatzolamide (generic)

diamox (brand name)

125 and 250 mg instant release oral

500 mg sustained release (sequels)  oral

500 mg vials for injection (for nauseas pts)

a pt who has a closed angle, what do you use: sustained release or instant release acetazolamide

125 or 250 mg instant release acetazolamide

methaxolamide (generic)

25 & 50 mg tablets oral

more potent 

neptazane (brand name)

dorzolamide

trusopt

2% opthalmic sol.

brinzolamide

azopt

1% ophthalmic susp.

cosopt

dorzolamide + timolol 

2% dorzolamide + 0.5% timolol sol.

clinical use for acetazolamide diamox

most widely used orally

250 mg every 6 hours or once 500 mg sustained release BID

if you have a sulfa allergy can you use acetazolamide

no

if you have a paba allergy can you use acetazolamide

yes

what is the peak plasma levels of acetazolamide

within 2-4 hours 

what is the maintenance of acetazolamide

4-6 hours

can you use acetazolamide during an acute angle attack

yes bc it has a fast onset of action

why do you have to use more acetazolamide than methazolamide

bc they are bound to plasma proteins so you need a bigger dose

is acetazolamide metabolized? and where is it excreted

it is not metabolized and it is excreted by the kidneys 

difficult on the kidneys :(

anything that is a diuretic ?

is hard on the kidneys

someone who is in acute angle closure what is their main side effect

nausea

so they will prob throw up the pill, that’s why you gotta do IV route 

how much do acetazolamide (an oral CAI) lowers the IOP

about 40% (HUGE decrease in IOP) but has a LOT of side effects

are oral CAIs better than prostaglandins

yea bc you know they acc took the pill and didnt miss their eye with the eye drop

clinical uses for acetazolamide

short term IOP reduction bc of the SIGNIFICANT ADVERSE RXNS

topical CAIs are much safer bc it doesnt do anything to the kidneys and metabolic acidosis so it is an alternative for long term use

acute angle closure glaucoma

may also produce a partial or complete resolution of macular edema in pts with CME, retinitis pigmentosa, and chronic intermediate uveitis 

we know that timolol has no effect on aqueous production when sleeping, but does acetazolamide do anything while we’re sleeping

yes and it can be used at night instead of timolol bc it wont cause a reduction in OPP or BP 

what is the difference between acetazolamide and methazolamide

same structure (be careful with sulfa allergy)

same onset of action time and peak

difference: less of methazolamide is bound to the plasma proteins so you can lower the dosage and it has a longer half life → only need 25-50 mg

produces less alteration of acid-base balance than acetazolamide and is more reasonable for pts with severe COPD

why is severe COPD a contraindication in pts using methazolamide

bc using CAIs can potentially increase CO2 which is not needed for pts already in respiratory issues, it can worsen their condition 

how many times should you dose methazolamide

TID

which is preferred acetazolamide or methazolamide

methaxolamide but it’s more expensive and isnt as readily available as acetazolamide

what are some common side effects of oral CAIs

numbness and tingling of fingers and mouth 

tastes like metal

GI irritation 

metabolic acidosis

decreased libido

depression

fatigue

malaise

weight loss 

what are some uncommon side effects of oral CAIs

hypokalemia

renal calculi (kidney stones)

blood dyscrasias

• thrmbocytopenia

• agranulocytosis

• aplastic anemia

dermatitis

what are some ocular effects of oral CAIs

transient myopia

when comparing acetazolamide to methazolamide, which one produces less systemic side effects

methazolamide 

contraindications to oral CAIs

anyone who is allergic to sulfas

preggo cat C

significant liver disease

kidney disease

SEVERE COPD

some secondary glaucomas

• NVG (neovascular glaucoma)

why is using CAIs not beneficial in someone with NVG

bc someone with neovascular glaucoma, the issue is blocking the TM

so suppressing aqueous outflow might not do much

what do topical CAIs do

they alter aqueous humor composition by:

• lowering pH

• decreasing bicarbonate levels

• increasing posterior chamber ascorbate levels limited to the eye receiving dose

dorzolamide (trusopt)

TID (every 8 hours)

effectiveness: not that good → 15-20% reduction in intraocular pressure

this shouldnt be rx’ed first line

better as adjunct med

does dorzolamide do anything during night time

yes, it decrease aqueous humor production at night

is there an additional effect of adding dorzolamide with latanoprost

no

what is the mechanism of dorzolamide

decrease in aqueous humor production

does trusopt sting

yes

bc it is on the acidic side

does azopt sting

no

what is the dosage of dorzolamide

TID is best but BID works too

max action: 2 hours after administration

does dorzolamide prevent IOP spikes post laser procedures?

it can but it isnt the first choice

we use apraclonidine, then beta blocker, then dorzolamide

brinzolamide

azopt

topical CAI

TID is FDA but used BID is ok too 

better tolerated on the eye (less stinging than dorzolamide)

comes in a suspension → needs to be shaken

what is the only glaucoma med that comes in a suspension and must be shaken prior to use

brinzolamide

what are the ocular side effects of using topical CAIs

irritation

STINGING

burning or foreign body sensation

blurry vision

SPK

corneal edema/decompensation

hypersensitivity rxn

what are some systemic side effects of using topical CAIs

bitter taste 

should you use a topical dorzolamide with an oral CAIs

No, it is not recommended due to increased risk of side effects.

what are some contraindication of using topical CAIs

sulfa allergy (low risk)

caution in pts with:

• severe impairment

• hepatic impairment

avoid in pts taking an oral CAI bc it doesnt do much