ROCLANDA

Indications

• Raised intraocular pressure in open-angle glaucoma
• Ocular hypertension

Dosage

Children: Child: Apply once daily, to be administered preferably in the evening.

Adults: Apply once daily, preferably in the evening.

Mechanism of action

Latanoprost selectively stimulates the prostaglandin F2 alpha receptor, leading to increased outflow of aqueous humor. This mechanism involves remodeling the extracellular matrix and regulating matrix metalloproteinases, which enhances tissue permeability and modifies outflow resistance, thus decreasing intraocular pressure (IOP).

Pharmacodynamics

Latanoprost effectively reduces intraocular pressure by enhancing uveoscleral outflow. The onset of action occurs within 3 to 4 hours, reaching its maximum effect at 8 to 12 hours post-administration, with activity maintained for approximately 24 hours. Notably, long-term use may cause changes in iris pigmentation and other ocular effects such as conjunctival hyperemia and eyelash changes in a small proportion of patients.

Pharmacokinetics

Latanoprost is administered as eye drops and is absorbed through the cornea. It undergoes hydrolysis to its active form, which then exerts its therapeutic effects. The drug's effects are most pronounced within the first 12 hours after administration, with a duration of action that supports once-daily dosing. It is important to note that the presence of benzalkonium chloride in some formulations may cause ocular irritation.

Contra-indications

• Active herpes simplex keratitis
• History of recurrent herpetic keratitis associated with prostaglandin analogues

Adverse effects

• Iris pigmentation
• Conjunctival hyperemia
• Pigmentation of periocular tissues
• Eyelash changes
• Hypertrichosis
• Ocular irritation
• Dizziness
• Headache
• Myalgia
• Chest pain
• Dyspnoea
• Unstable angina

Interactions

• May interact with thiomersal-containing preparations
• Use with caution in patients receiving other ocular medications

Precautions

• Do not use within 5 minutes of thiomersal-containing preparations
• Monitor patients with a history of significant asthma
• Use with caution in patients with angle-closure glaucoma or aphakia
• Consider risks for uveitis in predisposed individuals

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential effects.

Breast-feeding

May be present in breast milk; manufacturer advises caution.

Storage

Store at room temperature. Protect from light. Once opened, use within a specified time frame as indicated by the manufacturer.

Formulations

• Latanoprost 50 microgram per 1 ml eye drops
• Monopost 50 micrograms/ml eye drops
• Medizol 50 micrograms/ml eye drops
• Xalatan 50 micrograms/ml eye drops

Mechanism of action

Elevated intraocular pressure leads to an increased risk of glaucomatous visual field loss. The higher the intraocular pressure, the higher the risk of damage to the optic nerve and loss of visual field. Latanoprost selectively stimulates the prostaglandin F2 alpha receptor and this results in a decreased intraocular pressure (IOP) via the increased outflow of aqueous humor, which is often implicated in cases of elevated intraocular pressure. Possible specific mechanisms of the abovementioned increased aqueous outflow are the remodeling of the extracellular matrix and regulation of matrix metalloproteinases. These actions result in higher tissue permeability related to humor outflow pathways, which likely change outflow resistance and/or outflow rates.

Pharmacodynamics

Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow. A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours. **A note on eye and periorbital changes** Between 3 to 10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use. Patients should be notified of this risk before initiating treatment. It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group. This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation.

Mechanism of action

The medical condition glaucoma is a leading cause of progressive visual impairment and blindness across the world with primary open-angle glaucoma (POAG) being the major type of glaucoma. Elevated intraocular pressure (IOP) resulting from increased resistance to aqueous humor outflow is considered a major risk for the development and progression of POAG, but various clinical studies have demonstrated that the reduction and tight control of IOP can delay or prevent POAG and the vision loss associated with it. Ordinary physiological IOP results from aqueous humor produced by the ocular ciliary body and its outflow through two main outflow pathways: the conventional (trabecular) and the unconventional (uveoscleral) pathways. Under ordinary physiological conditions, diagnostic tracers have shown that the conventional trabecular pathway accounts for up to 90% of aqueous humor outflow. Through this pathway, aqueous humor drains from the anterior chamber sequentially through the uveal and corneoscleral meshwork beams, juxtacanalicular connective tissue (JCT) region, and inner wall (IW) endothelial cells of Schlemm's canal (SC) until finally entering the lumen of SC. From there aqueous humor drains into the collector channels, intravascular plexus, epscleral veins, and finally into the blood circulation. In glaucomatous eyes, elevated IOP is the result of abnormally increased resistance to aqueous outflow in the conventional trabecular pathway due to apparent increases in the contractile tone and stiffness of the trabecular pathway meshwork (TM), changes in extracellular matrix composition, and/or a decrease in the conductance of the IW endothelial cells of SC. Subsequently, as a rho kinase inhibitor, the novelty of netarsudil lies in its ability or specificity to apply its mechanism of action directly and specifically at the diseased TM of the conventional trabecular outflow pathway. In particular, rho kinases are serine/threonine kinases that function as important downstream effectors of Rho GTPase. Such activity in the TM and SC drives actomysin contraction, promotes extracellular matrix production, and increases cell stiffness. Acting as an inhibitor of rho kinase, netarsudil consequently reduces cell contraction, decreases the expression of fibrosis-related proteins, and reduces cell stiffness in the TM and SC cells. As a result, netarsudil has been able to demonstrate increases in trabecular outflow facility, increases in the effective filtration area of the TM, cause expansion of the TM tissue, and dilate episcleral veins. Furthermore, netarsudil is also believed to possess inhibitory action against the norepinephrine transporter (NET). Such inhibition of the NET prevents reuptake of norepinephrine at noradrenergic synapses, which results in an increase in the strength and duration of endogenous norepinephrine signaling. As a consequence of this enhanced signaling, norepinephrine-induced vasoconstriction that can reduce blood flow to the ciliary body may subsequently be responsible for a mechanism in which the formation of aqueous humor may be delayed, prolonged, or reduced as well.

Pharmacodynamics

Aqueous humour flows out of the eye via two pathways: 1) the conventional trabecular pathway and 2) the unconventional uveoscleral pathway. And, although it has been shown that the conventional trabecular pathway accounts for most aqueous outflow due to various pathologies, most medications available for treating glaucoma target the uveoscleral pathway for treatment and leave the diseased trabecular pathway untreated and unhindered in its progressive deterioration and dysfunction. Netarsudil is subsequently a novel glaucoma medication that is both a rho kinase and norepinephrine transport (NATs)s inhibitor that specifically targets and inhibits rho kinase and NATS found in the conventional trabecular pathway while many of its contemporaries offer therapy that focuses on cell and muscle tissue remodelling