lec 10: ocular hypotensive agents (rho kinase inhibitros)

rho kinase inhibitors

tophat: which med is most likely to have tachyphylaxis

apraclonidine

tophat: which med may be used long term orally due less systemic side effects

methazolamide

tophat: which med is likely to sting upon instillation due to lower pH

dorzolamide

tophat: which med is a formulation that may be used as a non-addictive vasoconstricter

brimonidine

tophat: which med includes angle closure glaucoma for sustained reduction in IOP

acetazolamide

tophat: which med is formulated as a suspension

brinzolamide 

what is a rho kinase inhibitor

netarsudil ophthalmic sol. 0.02% rhopressa

what is the mechanism of action of the rho kinase inhibitor

1. improves TM outflow through the trabecular meshwork and lowers episcleral venous pressure

2. norepinephrine transporter inhibition decreases fluid production

   1. rhopressa molecule goes in and it gets metabolized

how does netarsudil get metabolized

netarasudil gets broken down by carboxylesterase which breaks it into it’s active form netarsudil -M1

what is the active form that binds to rho kinase

netarsudil - M1

when rho kinase is around, what does it cause the muscles to do

contract

when you add a rho kinase inhibitor aka rock inhibitor, what happens

they bind to the rho kinase and the trabecular meshwork cant contract

it relaxes instead and causes large pores that aqueous can flow through , which lowers intraocular pressure

with the use of netarsudil what happens to the TM

it relaxes so there are larger spaces and aqueous humor can flow out more easily

what is the secondary action of netarsudil

decreases episcleral venous pressure 

since netarsudil increases TM outflow by 35%, does it also decrease IOP by 35%

no that is not the same thing

how does episcleral venous pressure work

aqueous fluid goes through TM and into schlemm’s canal and it eventually goes through the collector channels of the sclera and into the episcleral veins so if EVP is high, that pushes against fluid from going through

what is the EVP always around

8-10 mmHg

what is the IOP formula

IOP = F/V + IOP

if you can lower EVP, what happens to IOP

it also goes down 

where does rhopressa work

it works on EVP (decreases it) and works on outflow through the trabecular meshwork (increases outflow)

what drug is similar to rho kinase inhibitors in that it prevents norepinephrine from being reuptaken back into the presynaptic terminal

cocaine

if you inhibit norepi transporter, what happens

that means there is more norepinephrine around which binds to alpha1 and that reduces blood flow and reduced blood flow to ciliary body means IOP goes down

adding rhopressa to a prostaglandin, what happens

it causes an additional reduction of 4mmHg of IOP

what is the % reduction of rho kinase inhibitors

20% reduction in IOP

what are some clinical uses for rho kinase inhibitors

reduction of elevated IOP in pts with open angle glaucoma or ocular hypertension

what is the recommended dosage for rho kinase inhibitors

one drop in the affected eye once daily in the evening 

if you take rhopressa with a prostaglandin (sep bottles) how do you dose em

dose em separate, 10-15 min apart

never dose them at the same time

what are the common side effects of rho kinase inhibitors 

CONJUNCTIVA HYPEREMIA IS EXTREME

corneal verticillate

instillation site pain

conj hemorrhage

why do rho kinase inhibitors cause SUCH bad conj hyperemia

bc they dilate the conjunctival blood vessels so that’s why they cause a RED eye

what are the less common side effects of rho kinase inhibitors 

redness

corneal staining

blurry vision

increased lacrimation

redness of the eyelid