Toxic Epidermal Necrolysis Induced: DISCUSSION
Brinzolamide and dorzolamide are highly specific topical CAIs, which lower intraocular pressure (IOP) by reducing the rate of aqueous humour formation. Although systemic CAIs are the most potent medications for lowering intraocular pressure for primary open-angle glaucoma and other conditions with ocular hypertension, many cases with adverse systemic reactions have been reported, including Stevens-Johnson syndrome (SJS), TEN, fulminant hepatic necrosis, aplastic anemia, drug hypersensitivity, metabolic acidosis, serum sickness and nephritis. Therefore, topical application of intraopthalmic CAIs is recommended to control intraocular pressure, as this route of administration lowers ocular hypertension without serious adverse reactions.
In healthy people, topical CAIs can enter the blood circulation via ocular structures, such as the conjunctiva, cornea and lens. However, the blood level is not high enough to cause adverse reactions. Yet, topical CAIs have the potential to induce SJS-TEN in patients, as they are sulfonamide derivatives that behave similarly to systemic sul- fonamide. Metabolic inactivation of topical CAIs occurs primarily in the liver through oxidative O- and N-dealkylation by cytochrome P450 isoenzymes, and metabolites are eliminated primarily in the urine. Therefore, brinzolamide is not recommended in the USA and in Europe for the treatment of patients with severe renal impairment (creatinine clearance <30 ml/min). In patients with hepatic impairment, topical CAIs are not recommended, or they should be used with caution, because of abnormal pharmacokinetics in such patients.
For our patients, both had liver disease; one had cirrhosis and the other had an inactive hepatitis B. The use of topical CAIs was dangerous in these patients with underlying liver diseases, as they were at risk for developing SJS-TEN. In the der- matological literature, 1 case of TEN was reported, for which dorzolamide was the suggested cause. However, the patient was also medicated with timolol and latanoprost. The experience with our 2 cases confirmed that both brinzolamide and dorzolamide could induce TEN when used as topical CAIs, as our patients only received these topical CAIs. In the ophthalmology literature, TEN has been reported to be induced by other topical ophthal- mologic agents with a fumigant mixture and perfume.
silagra tablets
As to the mechanism to induce TEN, the reactive metabolites of sulfonamides are known to cause idiosyncratic reactions. If the metabolites are not detoxified properly, they can act as a hapten that binds with endogenous proteins, which then triggers an immune reaction. Haptenated compounds may also be directly toxic to cells. These 2 cases illustrate that topical CAIs can induce TEN similar to that by systemic sulfonamides. There are several reports of SJS or TEN after taking systemic CAI, especially among Asians. CAIs are sulfonamide derivatives. Whether taken systemically or as a topical agent, the risks for developing SJS or TEN can be the same.
