Clinical observation of Metazolamide in the treatment of normal pressure hydrocephalus / 中华老年医学杂志

Objective:To study the efficacy and safety of Methazolamide(MTZ)for the treatment of normal pressure hydrocephalus(NPH)patients.Methods:A randomized, double-blind, placebo-controlled, prospective clinical study was conducted in Aviation General Hospital.A total of 35 NPH patients including 29 idiopathic normal pressure hydrocephalus(iNPH)and 6 secondary normal pressure hydrocephalus(sNPH)received drug treatment in our hospital from September 2019 to March 2021.All patients were unsuitable for or refused surgical treatment for some reasons.The patients were divided into drug group(n=18)and control group(n=10), taking oral MTZ or placebo 25 mg twice daily, increasing to 50 mg twice daily after 1 week if there was no discomfort.The 10 m gait score, cognitive function score, brain MRI check were completed before and 1 month after oral administration.The assessment of idiopathic normal pressure hydrocephalus scale(iNPHGS)score were performed 1 month and 3 months after oral administration.The primary efficacy endpoint was iNPHGS score for 3 months treatment and the secondary efficacy endpoint was the assessment of above scales for 1 month treatment.Results:As compared with baseline, the effect of 1 month treatment showed that MOCA scores[(16.2±8.8)and(14.8±8.7)scores, t=-2.68, P=0.02], 10 m gait scores[(22.3±11.2)and(25.6±12.9), t=2.76, P=0.02], iNPHGS scores[(7.3±3.2)and(8.1±3.5), t=4.08, P<0.01]were improved.The effect of 3 month treatment showed that the iNPHGS score(6.1±2.4)was improved compared with baseline( t=5.07, P<0.01)and 1 month( t=4.11, P<0.01). But the above scores of the control group were not significantly improved compared with the baseline(all P>0.05). After 1 month treatment, the 10 m gait score and iNPHGS score in the drug group were improved compared with those in the control group(all P<0.05). After 3 months treatment, the iNPHGS score was improved compared with the baseline level in the control group( t=-4.41, P<0.05). The above 35 patients had no serious adverse reactions such as hypokalemia and acidosis.There was no significant difference in adverse events between the two groups( χ2=0.01, P=1.00). Conclusions:The treatment of MTZ could effectively improve the clinical symptoms of NPH patients with good safety.

Application of 13N-Ammonia PET/CT Cerebral Blood Perfusion Imaging Combined with Methazolamide Challenge in Ischemic Cerebrovascular Diseases / 中国康复理论与实践

Objective:To apply 13N-ammonia PET/CT cerebral blood perfusion imaging combined with methazolamide challenge for cerebrovascular reserve (CVR) evaluation in ischemic cerebrovascular diseases. Methods:From January, 2014 to December, 2016, 56 ischemic stroke patients with serious stenosis of unilateral internal carotid artery or middle cerebral artery accepted basal and stress PET/CT with methazolamide challenge. The patients were divided into normal-CVR group (n = 29) and reduced-CVR group (n = 27) according to the results of CVR, and followed up for 24 months. The ischemic cerebrovascular events and cerebral blood flow were observed. Results:The incidence of transient ischemic attack was more in the reduced-CVR group than in the normal-CVR group (χ2 = 4.389, P < 0.05), while the incidence of ischemic stroke increased a little with no significant difference between the two groups (P > 0.05). The CBF was improved in normal-CVR group after treatment (t = 2.409, P < 0.05), and the improvement was not significant in reduced-CVR group (t = 0.648, P > 0.05). Conclusion:13N-ammonia PET/CT cerebral blood flow perfusion imaging combined with methazolamide challenge can be used to evaluate CVR to predict the outcome for patients with cerebral ischemic disease, which is helpful for early intervention.

Effect of methazolamide in patients with refractory uveitic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the efficacy and safety of methazolamide in treating refractory uveitic macular edema.METHODS: Retrospective self-controlled study was designed.A total of 15 patients (20 eyes) with refractory uveitic macular edema which used methazolamide as adjuvant therapy were enrolled in Shanghai First People`s Hospital from January 2015 to June 2016.The changes of central macular thickness (CMT) and best corrected visual acuity (BCVA) were observed at baseline and 2, 4, 8wk after treatment.We also focused on the incidence of complications and relapse.RESULTS: The CMT was 445.95±154.10μm, 338.83±138.34μm, 251.50±40.20μm, 244.90±35.68μm at baseline, 2, 4 and 8wk after treatment, respectively.The differences among them were statistically significant (F=15.467, P<0.05).The BCVA (log MAR) were 0.40±0.17, 0.28±0.21, 0.19±0.20, 0.18±0.21 at baseline, 2, 4 and 8wk respectively, with a significant difference among them (F=5.208, P<0.05).When the cumulative dose reached to 700mg and 1400mg, no one had methazolamide-related complications;and when it came to 2800mg, 5 patients (33%) had methazolamide-related complication.After the withdrawal of methazolamide 1wk, 1 and 3mo, 3 patients (20%), 5 patients (33%) and 8 patients (53%) relapsed, respectively.CONCLUSION: Methazolamide is beneficial in improving macular edema and vision in 4wk.When the cumulative dose is more than 1400mg, we need pay attention to the complications.After discontinuing methazolamide for 1wk, macular edema relapsed in some patients, and more than half of patients recurred after 3mo.So the patients should be followed closely in 3mo after withdrawal of methazolamide.

Angle Closure and the Acute Rise of Intraocular Pressure after Administration of Methazolamide

PURPOSE: To report a case involving an unexpected increase in intraocular pressure (IOP) and acute angle closure after oral administration of methazolamide. CASE SUMMARY: A 38-year-old male visited the emergency department complaining of decreased visual acuity (VA) and ocular pain. These symptoms developed after he took two tablets of 50 mg methazolamide because his IOP was above normal after a short course of systemic steroid treatment. His uncorrected VA dropped to 0.04 and the refractive error was −6.5 diopters in both eyes. The anterior chamber was very shallow, and the IOPs were 46 mmHg in the right eye and 42 mmHg in the left eye. Macular retinal folds were observed in both eyes in infrared fundus images. The patient was instructed not to take methazolamide, which was suspected as the cause of this idiosyncratic drug reaction. He was prescribed topical anti-glaucoma medications and cycloplegics to relieve the acute angle closure, and all symptoms disappeared after these treatments. CONCLUSIONS: Methazolamide is a sulfa derivative like topiramate, which can cause acute angle closure involving edema of the ciliary body and anterior displacement of the lens-iris diaphragm. Clinicians should consider this possible IOP increase before prescribing methazolamide.

Cerebrovascular Reserve in Patients with Unilateral Internal Carotid Artery or Middle Cerebral Artery Stenosis: Study with 13N-Ammonia PET/CT Combined with Methazolamide / 中国康复理论与实践

@#Objective To evaluate the cerebrovascular reserve (CVR) with 13N-ammonia PET/CT and methazolamide in patients with cerebral ischemic disease. Methods From January, 2014 to December, 2015, basal and stress PET/CT were performed in ten healthy persons and 53 patients with unilateral internal carotid artery or middle cerebral artery stenosis. Radioactive counts were measured on mirror regions of bilateral frontal lobe, parietal lobe, temporal lobe, occipital lobe, basal ganglia and thalamus to calculate the blood flow change rate. Results For the healthy persons, the radioactive distribution of bilateral frontal lobe, parietal lobe, temporal lobe, occipital lobe, basal ganglia and thalamus were roughly symmetrical on both basal and stress PET/CT. The radioactive counts were more in basal ganglia and thalamus than in cortex, and the least in white matter. The radioactive counts were more on stress PET/CT than basal PET/CT, and there was no significant difference between both sides (t=1.552, P=0.132). For the patients, the blood flow perfusion decreased in 39 patients with 126 regions on basal PET/CT, and 49 patients with 183 regions on stress PET/CT. Within the 39 patients who found decreased blood flow perfusion regions, 16 patients were found new regions on stress PET/CT, and 29 regions of 13 patients improved in blood flow perfusion on stress PET/ CT. The blood flow change rate was significantly different between basal and stress PET/CT (t=2.466, P<0.05). Conclusion 13N-ammonia PET/CT cerebral blood flow perfusion imaging combined with methazolamide stress test can evaluate the cerebrovascular reserve in patients with unilateral internal carotid artery or middle cerebral artery stenosis, and is valuable for clinical assessment and early intervention for patients with cerebral ischemic disease.

Methazolamide-induced toxic epidermal necrolysis confirmed by lymphocyte activation test

Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.

Methazolamide-induced toxic epidermal necrolysis in a patient with HLA-B5901 allele / 中华皮肤科杂志

A 56-year-old female patient of Han nationality presented with generalized erythema and vesicles for 6 days,as well as high fever for 2 days.Twenty days prior to hospitalization,the patient received surgical treatment combined with oral methazolamide and glucocorticoids for glaucoma.The patient had a history of allergy to sulfanilamides.On admission,the patient presented with generalized erythema,vesicles and occasional erosions with bilateral eyelid and oral involvement.Nikolsky's sign was positive.Wheezing sound was heard over the right lung.Genetic testing showed that HLA-B5901 allele was positive.The patient was diagnosed with methazolamide-induced toxic epidermal necrolysis (TEN) complicated by pneumonia,and managed with immunoglobulin (25 g/day,5 days),glucocorticoids (the largest dose equivalent to methylprednisolone 160 mg/day),fresh plasma,antibiotics,as well as other supporting and symptomatic treatments.The condition was controlled after 2 weeks,and the patient was cured and discharged from hospital after 25 days.The fact that the patient carried HLA-B5901 allele suggests that HLA-B5901 is strongly correlated with methazolamide-induced TEN or Stevens-Johnson syndrome in Chinese descendants or Han population,besides in Japanese and Korean descendants.

Protective effects of methazolamide on acute exposure to high altitude / 中国药学杂志

OBJECTIVE: To investigate the effect of acute exposure to 4300 m altitude environments on the body pathophysiological, serum, TNF-α and IL-1β of Wistar rats and protective effect of methazolamide on Wistar rats. METHODS: Twenty-eight Healthy adult Wistar rats were randomly divided into plain (altitude of 55 m) control group, high altitude (altitude of 4300 m) model group, high altitude methazolamide group, and high altitude acetazolamide group. After being intragastric administration with 0.9% sodium chloride injection, methazolamide (2 times a day, 2.23 mg·kg-1) and acetazolamide (2 times a day, 22.33 mg·kg-1) for 5 consecutive days. The biochemical, blood gas, the pathological results of rats were analyzed. The TNF-α and IL-1β content were detected from the blood samples. RESULTS: Blood and biochemical results showed the high altitude might cause dehydration in rats. Compared with the plain control group, each index of the high altitude model group changed significantly (P<0.01), compared with the high altitude group, the aspartate transaminase (AST), alanine aminotransferase (ALT), pH value, bicarbonate concentration (cHCO3-), buffer base (BB), base excess (BE) of methazolamide and acetazolamide group were significantly decreased (P<0.01), indicated that methazolamide and acetazolamide had protective effect on rat liver.The total protein (TP), urea solution (UREA), partial pressure of carbon dioxide (PaCO2), sodium concentration (cNa+), chloride concentration (cCl-) were significantly increased (P<0.01), indicated that the high altitude group had metabolic acidosis and respiratory alkalosis, and liver and lung tissue had pathological damaged.Compared with the acetazolamide group, the methazolamide group damaged less.Compared with plain control group, serum TNF-α of high altitude groups significantly increased, IL-β of high altitude groups decreased significantly, which, serum TNF-a, IL-1β levels of acetazolamide and methazolamide group were significantly higher than high altitude model group (P<0.01). CONCLUSION: Methazolamide can improve acute high altitude physiological and biochemical status of rats, reduce inflammatory injury, with a good protective effect of hypoxia.

Five Cases of Stevens-Johnson Syndrome May Be Associated with Methazolamide Treatment / 대한피부과학회지

Recently, Stevens-Johnson syndrome associated with methazolamide has been reported in Koreans, more frequently. Methazolamide is a carbonic anhydrase inhibitor commonly used for lowering intraocular pressure in glaucoma and other ophthalmologic diseases. We reported five cases of Stevens-Johnson syndrome induced by methazolamide. All patients showed atypical clinical manifestations, compared to classical Stevens-Johnson syndrome. Methazolamide induced Stevens-Johnson syndrome showed scattered or confluent maculopapular eruptions initially, which are similar to morbiliform drug eruption with mild lip erosion and palmar erythema. Even though there was no skin erosion initially, it showed rapid progression to severe erosion on the trunk and palmoplantar erythema within 5 to 7 days. Therefore, our data indicated that methazolamide induced Stevens-Johnson syndrome should be checked for a patient who has a history of ophthalmologic treatment with a drug eruption like skin lesion.

A Case of Paclitaxel-induced Maculopathy Treated with Methazolamide

A 54-year-old female patient who had been undergoing anti-cancer chemotherapy and radiotherapy for seven years after surgery for left breast cancer visited our clinic for visual disturbance in the right eye at nine months after paclitaxel administration. The best-corrected visual acuity was 0.5 in the right eye and 1.0 in the left eye. The patient was diagnosed with maculopathy due to paclitaxel administration based on the finding of cystoid macular edema in the right eye on fundus examination and optical coherence tomography; however, no leakage was detected on fluorescein angiography. Thus, drug replacement was planned. On the other hand, no abnormal finding was observed in the left eye. However, as the anti-cancer effect of paclitaxel is significant, replacing paclitaxel with another agent was not warranted; therefore, maintenance therapy with methazolamide was performed before and after administering the anti-cancer agent. Aggravation of cystoid macular edema was prevented, and vision improvement was achieved by oral maintenance therapy with methazolamide. In addition, the same fundus findings as shown in the right eye were detected in the left eye at 16 months after paclitaxel administration. After administering methazolamide, macular thickness was reduced, and vision was improved in the left eye. Paclitaxel administration was discontinued due to cutaneous metastasis from the breast cancer, and another anti-cancer agent was then administered. No subsequent cystoid macular edema has occurred.

Epidermal Necrolysis due to Methazolamide Treatment in Glaucomatous Patients / 대한피부과학회지

Epidermal necrolysis (EN) is a rare, but potentially life threatening disease, characterized by epidermal necrosis and sub-epidermal detatchment, and is predominantly medication-induced. Methazolamide is a sulfonamide derivative and carbonic anhydrase inhibitor used for lowering of intraocular pressure in glucomatous patients. Common side effects of methazolamide include metabolic acidosis, hypokalemia, tinnitus, transient myopia, and renal calculi; however, EN caused by methazolamide is very rare. We report on two cases of EN induced by methazolamide treatment and review previously published cases.

Comparison of Methazolamide and Acetazolamide for Prevention of Acute Mountain Sickness in Adolescents

PURPOSE: Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2500 m. Acetazolamide, a carbonic anhydrase inhibitor (CAI), is recommended for AMS prophylaxis, but may have adverse effects such as paresthesia. Methazolamide has the same pharmacologic effect, but diffuses more rapidly into tissue and is more potent than acetazolamide. But, little is known about methazolamide as an AMS prophylactic agent. This study was conducted to prospectively compare metazolamide with acetazolamide for its preventive effect for AMS in adolescents. METHODS: Nineteen adolescents aged 13~18 years attempting an ascent of Mt. Kalapatar (5500 m) were randomly divided to receive acetazolamide (n=10) or methazolamide (n=9). Oxygen saturation (SpO2) and pulse rate were measured at each altitude. The incidence of AMS was calculated using the Lake Louise questionnaire. Difference in incidence between two groups was analyzed using generalized estimating equation. Difference in Lake Louise scores (LLS) was analyzed using linear mixed model testing. RESULTS: Overall incidence of AMS was 68.4%. Fatigue or malaise was the most frequent symptom (94.7%) followed by headache (84.2%). SpO2 decreased as the altitude increased (p<0.001). There was no difference in SpO2 and pulse rate between the two groups (p=0.44). There was no difference in LLS (p=0.22) and incidence of AMS (p=0.07) between the two groups with increasing altitude. Paresthesia was less common in the methazolamide group, but was not statistically different (p=0.35). CONCLUSION: Methazolamide is equally effective as acetazolamide in preventing AMS among adolescents.

Methazolamide-induced Stevens-Johnson Syndrome

PURPOSE: To report three consecutive cases of methazolamide-induced Stevens-Johnson syndrome. CASE SUMMARY: We describe three patients who were all prescribed methazolamide for treatment of ophthalmologic conditions. A 29-year-old man and a 47- year-old woman were prescribed methazolamide (100 mg/day) for the treatment of central serous chorioretinopathy (CSCR). A 66-year-old woman was prescribed methazolamide (100 mg/day) for acute glaucoma of the left eye for approximately two weeks. After taking the methazolamide, three patients were showed the pururitic maculopapular rashes on the whole body and the vesicular eruptions of the oral mucosa and conjunctiva. On the basis of medication histories, characteristic skin lesions and mucosal involvement, we diagnosed all three patients with methazolamide-induced Stevens-Johnson syndrome. All three patients were hospitalized and treated with intravenous steroids and antihistamines. Two of the three cases showed conjunctival pseudomembranes. In two cases, the skin lesions worsened during the first week of treatment, and then resolved without complications over the next two to three weeks. The condition of the 47-year-old female patient deteriorated rapidly to toxic epidermal necrolysis due to sensitivity to sulfa antibiotics. HLA- A24, B59 and Cw1 were detected in all three cases. CONCLUSIONS: In 2008, domestic production of acetazolamide was halted in Korea. Because of this, methazolamide is expected to be prescribed by ophthalmologists more commonly than in previous years. Complete medical histories should be taken before prescribing methazolamide to patients. HLA typing should be conducted whenever possible to screen patients before prescription of methazolamide.

Two Cases of HLA-B59(+) Stevens-Johnson Syndrome (SJS)-Toxic Epidermal Necrolysis (TEN) Associated with Methazolamide Treatment / 대한피부과학회지

Methazolamide is a sulfonamide derivative and carbonic anhydrase inhibitor used to lower intraocular pressure in glaucomatous eyes. Stevens-Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) associated with methazolamide treatment has been reported in Korean and Japanese patients. We report two cases of SJS-TEN associated with methazolamide treatment. The result of HLA typing of our two patients was a positive reaction for HLA-B59, which is specific to Koreans and Japanese. This suggests a possible relationship between genetic background and SJS-TEN associated with methazolamide treatment. Therefore, methazolamide should be prescribed with caution to Korean or Japanese patients.

Preparation and Quality Control of Methazolamide Eye Drops / 中国药房

OBJECTIVE: To prepare methazolamide eye drops and establish its quality control method.METHODS: Methazolamide eye drops was prepared using inorganic nanoparticles as carrier and methazolamide as principal agent.The content of methazolamide was determined by ultraviolet spectrophotometry.The stability of the preparation was investigated. RESULTS: The preparation was white suspension andin conformity with the description ofChina Pharmacopeia(2005 edition) inidentification and test.The linear concentration range of methazolamide was4~12?g.mL-1(r=0.999 9) and the average recovery was100.10% (RSD=1.11%).Methazolamide eye drops was unstable under highlight , while all the test items had no significant change in6-month accelerated test.CONCLUSION: The preparative method is si mple and feasible and the quality of the preparationis stable and controllable.But the preparation should be stored away formlight.

Four cases of Stevens-Johnson Syndrome associated with Methazolamide Treatment / 대한피부과학회지

Methazolamide is a carbonic anhydrase inhibitor commonly used for lowering intraocular pressure in glaucoma and other ophthalmologic diseases. Carbonic anhydrase inhibitors are sulfonamide derivatives that are known to cause many adverse side effects, including dermatologic reactions. Recently, Stevens-Johnson syndrome (SJS) associated with methazolamide treatment has been reported in Japanese and Japanese Americans, and it suggested a relationship between genetic background and methazolamide-induced SJS. We report four cases of SJS induced by methazolamide. Methazolamide should be prescribed with caution in patients of Japanese or Korean descent.

Association of HLA Type with Stevens-Johnson Syndrome Induced by Methazolamide Treatment

There have been reports between Stevens-Johnson syndrome (SJS)induced by methazolamide treatment and genetic background especially in Japanese and Korean descent.We report 6 cases of SJS and the results of HLA (human leukocyte antigen)typing that suggest a relationship between genetic background and SJS induced by methazolamide treatment. We observed 6 patients as the subjects of this research, who had been suffering from SJS induced by methazolamide treatment at the Department of Ophthalmology, Catholic University.SJS appeared about 2 weeks after the patient started taking methazolamide (100 or 200 mg/d).After 15~30 days of treatment, they recovered with no serious complication.The results of HLA typing carried out 6 patients that all of the patients had HLA-A2, 5 patients were HLA-Cw1 and HLA-B59. Methazolamide should be carefully prescribed in patients of Japanese or Koreans descent and should not prescribe sulfonamide in SJS patients. A further systematic research on more cases is required to explaining ethnic peculiarity of the syndrome.

Three Cases of Stevens-Johnson Syndrome Associated with Methazolamide Treatment

There have been recent reports on the increasing number of Stevens-Johnson syndrome cases resulting from methazolamide and its relatively higher incidence in Japanese and Korean than any other people. The objective of this study is to examine its developement potential in Korean people.We observed three patients as the subjects of this research, who had been suffering from skin eruption during glaucoma treatment in the Department of Ophthalmology Catholic University, College of Medicine. All of them, for lowering IOP, took methazolamide 50mg a day for more than two weeks, but they had no history of systemic disease but glaucoma or hypersensitivity induced by other medications. With regard to their skin, vesicular eruption came out in their whole body and particularly oral mucosa severely. Also, systemic symptom such as slight fever and general malaise was accompained . However, by quitting the use of methazolamide and medicating corticosteriods instead, they recovered with no serious complication.It can be concluded, therefore, that they had Stevens-Johnson syndrome mainly by methazolamide based on the condition of their skin eruptionand the fact that they got well again by stopping the use of methazolamide on which they chiefly relied. However, a further systematic research on more cases os required with a view to elucidating confirmatory diagnosis and ethnic pecularity of the syndrome.