[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.

A much smaller portion (approximately 20%) reported corneal verticillata, instillation site pain, and conjunctival hemorrhages. Rho kinase inhibitors help lower IOP by increasing AH outflow, reducing AH production, and decreasing episcleral venous pressure (EVP) [36].

A Rho kinase inhibitor produces relaxation by 'calcium desensitization' [24]. Figure 2 shows that myosin light chain phosphatase is a target of the Rho/ROCK pathway. Inhibition of Rho kinases reduces myosin light chain phosphorylation thus producing relaxation.

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.

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.

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.

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!

Why does IOP increase in eyes? ›

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.

Two commonly used RKIs are Ripasudil (K-115) and Netarsudil(AR-13503). Ripasudil has been clinically approved to treat glaucoma in Japan. Side effects of Ripasudil include dose-dependent conjunctival hyperemia and non-dose dependent conjunctival hemorrhage. It has not shown any other ophthalmological side effects.

Rho kinase (ROCK) inhibitors, a novel class of drugs approved by the American Food and Drug Administration (FDA) in 2017, act directly on TM cells to reduce intraocular pressure (IOP) [11,12].

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.

The E. coli Rho factor is a hexameric protein required for transcription termination at certain cytosine-rich sites (reviewed in [33,34]). When bound to nascent RNA, Rho translocates towards the 3′ end until it reaches the transcription complex, where it unwinds the RNA–DNA duplex using ATP as an energy source [35].

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.

Severe hypotension (low blood pressure) Dizziness. Headache. Angioedema (accumulation of fluid cause swelling of the area below the skin or mucosa)