[PDF] Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. | Semantic Scholar (2024)

FAQs

What are the side effects of rho kinase inhibitors? ›

All in all, adverse events associated with ROCK inhibitors include conjunctival hyperemia, conjunctival hemorrhage, cornea verticillata, conjunctivitis, and blepharitis.

conclusions. Administration of Y-27632 caused a reduction in IOP and an increase in the outflow facility.

The mechanism of ROCK inhibitors' ability to decrease IOP is through direct action on the trabecular meshwork and Schlemm's canal cells (increases permeability), which play a large role in the resistance of aqueous humor outflow.

Rho kinase inhibitors work to treat diabetic retinopathy by decreasing the adhesion of leukocytes and by slowing leukocyte-induced damage. Used as an intravitreal injection, the Rho kinase inhibitor slows the synthesis of various downstream proteins in the Rho pathway as well as ICAM-1.

However, KIs have important side effects, including fatigue, hypertension, rash, impaired wound healing, myelosuppression, and diarrhea (14). The overall toxicity of KIs, although less life-threatening than conventional cytotoxic chemotherapy, nevertheless is common and may require dose reduction.

Local adverse effects, however, including conjunctival hyperemia, subconjunctival hemorrhages and cornea verticillata, are common. Development of Rho kinase inhibitors targeted to the cells of the outflow pathway and the retina may allow these agents to have even greater clinical impact.

Rho-associated kinase (Rho-kinase/ROCK/ROK) is an effector of the small GTPase Rho and belongs to the AGC family of kinases. Rho-kinase has pleiotropic functions including the regulation of cellular contraction, motility, morphology, polarity, cell division, and gene expression.

Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway.

Studies show that you can lower your intraocular pressure, or IOP, by doing exercises that raise your pulse by only twenty percent. You can do that easily with a twenty-minute walk, four times a week. If the weather outside is frightful, simple indoor calisthenics or yoga can do the trick, too!

It arises when fluid doesn't drain out of the eye at its regular rate, resulting in a buildup that increases intraocular (within the eye) pressure. Ocular hypertension may be an early sign of glaucoma, an eye disease that can cause irreversible vision loss over time if it is not treated.

What brand are rho kinase inhibitors? ›

Commonly Used Rho Kinase Inhibitors

Two commonly used RKIs are Ripasudil (K-115) and Netarsudil(AR-13503). Ripasudil has been clinically approved to treat glaucoma in Japan.

Currently, approved ROCK inhibitors in the market include ripasudil (Glanatec^®), netarsudil (Rhopressa^®), and the fixed combination of netarsudil/latanoprost (Rocklatan^®, Roclanda^®). They have all been proven to significantly reduce IOP with acceptable side effects, primarily mild to moderate conjunctival hyperemia.

The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases.

These side effects include cardiovascular conditions, blood clots, cancer and serious infections..

In Sept, 2021, the FDA expanded their safety warnings to the JAK inhibitor class. Similarly, in Nov, 2022, the EMA updated their recommendation on JAK inhibitors, suggesting they should only be prescribed in patients at high risk if no suitable alternatives are available—a devastating blow to many patients.

Those treatment side effects may range from mild skin rashes to life-threatening skin issues like Steven-Johnson syndrome/toxic epidermal necrosis. Another group of TKIs that target non-small lung cancer and colorectal cancer may cause cardiovascular issues like high blood pressure (hypertension) and proteinuria.