Nasolacrimal Occlusion Research Articles

Therapeutic regimens may change with nasolacrimal occlusion

Therapeutic regimens may change with nasolacrimal occlusion

Therapeutic Index of Pilocarpine, Carbachol, and Timolol With Nasolacrimal Occlusion

We assessed the effect of nasolacrimal occlusion on the therapeutic index of various antiglaucoma medications in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion used with pilocarpine 2% every 12 hours gave the maximal ocular hypotensive response. Carbachol 1.5% every 12 hours with nasolacrimal occlusion gave the maximal response for this drug. For timolol, nasolacrimal occlusion collapsed the dose-response curve and extended the duration of action. A final trial of carbachol added to timolol with nasolacrimal occlusion showed that timolol 0.25% and carbachol 1.5% every 12 hours gave the maximal response for this combination. Our findings suggest that most of the commercially used ocular hypotensive agents can achieve the same maximal effect with lower concentrations and less frequent administration (never exceeding every 12 hours) than are currently recommended should nasolacrimal occlusion be performed. Furthermore, nasolacrimal occlusion should markedly decrease the systemic absorption of topical ocular drugs and lessen the chance of systemic side effects.

Therapeutic Index of Epinephrine and Dipivefrin With Nasolacrimal Occlusion

We assessed the effect of nasolacrimal occlusion on the therapeutic index of the adrenoreceptor agonists in healthy volunteers and patients with glaucoma. Nasolacrimal occlusion did not significantly alter the response to 2% epinephrine or to 0.1% dipivefrin in healthy subjects, suggesting that both 2% epinephrine and 0.1% dipivefrin are at the top of the dose-response curve. When 0.5% epinephrine with nasolacrimal occlusion was tested in patients with glaucoma, effects were noticeable at four and eight hours (P less than .05), but not at 12 hours. For 2% epinephrine, there was no significant difference at any measurement time. Epinephrine (1%) with and without nasolacrimal occlusion gave results similar to those of 2% epinephrine, suggesting that 1% epinephrine is also at the top of the dose-response curve. Nasolacrimal occlusion did not increase the ocular hypotensive effect of either of these concentrations. Because dipivefrin, the most widely used formulation in this class, is a prodrug of epinephrine that has a corneal penetration approximately 17 times that of epinephrine, 0.05% dipivefrin, every 12 hours, might be an adequate dosage for maximal effect. Although nasolacrimal occlusion did not alter the drug effect of 0.1% dipivefrin, preventing as much drug as possible from reaching the systemic circulation is desirable.

Effect of Nasolacrimal Occlusion on Timolol Concentrations in the Aqueous Humor of the Human Eye

We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90min after instillation and also at 180min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest ~1h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups.

Side Effects and Ways to Avoid Them

Pilocarpine, a parasympathomimetic drug used in the treatment of glaucoma, produces a variety of ocular and systemic adverse reactions. Ocular side effects include miosis, accommodative spasm, frontal headaches, twitching lids, conjunctival injection, cataractous changes, allergic reactions, iris cysts, retinal detachment, increased permeability of the blood-aqueous barrier, anterior chamber narrowing, and the potential for inducing an acute angle-closure attack. Systemic side effects include nausea, vomiting, tenesmus, abdominal spasm, salivation, lacrimation, sweating, pulmonary edema, and bronchial spasm. The systemic side effects can best be minimized initially through proper use of the medication and nasolacrimal occlusion. The Ocusert,® a long-acting pilocarpine-incorporated ocular insert, is a recent advance in delivery technique that offers an adequate hypotensive action with fewer side effects. Pilopex® is a promising new experimental pilocarpine polymer salt presently being studied in Israel. Photomydriasis, a process involving the use of a laser to enlarge miotic pupils also offers help for these patients. N-demethylated carbachol is a new parasympathomimetic drug currently under study for glaucoma therapy. Initial results show that it may have considerable ocular hypotensive action with fewer adverse effects.