dorzolamide and Drug-Related-Side-Effects-and-Adverse-Reactions

Carbonic anhydrase inhibitors (CAIs) of the sulfonamide and sulfamate type are clinically used drugs as diuretics, antiglaucoma, antiepileptic, antiobesity and anti-high altitude disease agents. Anticancer agents based on CAIs are also in clinical development for the management of hypoxic, metastatic tumors. Acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide are mainly used as antiglaucoma drugs, sulthiame, topiramate and zonisamide as antiepileptic/antiobesity agents, celecoxib and polmacoxib are dual carbonic anhydrase/cycloxygenase inhibitors. Girentuximab, a monoclonal antibody and SLC-0111, a sulfonamide inhibitor, are in clinical trials as anticancer agents.. The drug interactions with many classes of pharmacological agents are reviewed. Some of these drugs, such as acetazolamide, topiramate and celecoxib show a large number of interactions with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, antiepileptics, immunosupressants, anticholinesterase drugs, β-blockers, anesthetics, oral contraceptives, anticancer agents, antifungals, anti-mycobacterials, lithium, metformin and clopidogrel.. The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high. There are also synergistic effects between CAIs and some NSAIDs, anticancer agents and benzodiazepines for the management of cystoid macular edema, some tumor types and neuropathic pain, respectively.

Topics: Acetazolamide; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Antibodies, Monoclonal; Anticonvulsants; Antineoplastic Agents; Benzodiazepines; Carbonic Anhydrase Inhibitors; Celecoxib; Clinical Trials as Topic; Contraindications; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Fructose; Humans; Isoxazoles; Methazolamide; Phenobarbital; Sulfanilamide; Sulfanilamides; Sulfonamides; Sulfonic Acids; Thiazines; Thiophenes; Topiramate; Zonisamide

To report two cases with corneal sterile infiltration presumably due to topical ocular hypotensive agent.. Case report.. Case 1: A 65-year-old man presented with corneal opacity and neovascularization in his left eye. A diagnosis of glaucoma was made 2 years previously, and anti-glaucoma agents were prescribed (brimonidine tartrate, ripasudil hydrochloride hydrate, and brinzolamide) for both eyes. Case 2: A 75-year-old woman noticed corneal opacity in the left eye. A diagnosis of glaucoma was made 35 years previously, and anti-glaucoma agents were prescribed (brimonidine tartrate, 1% dorzolamide, and bimatoprost) for both eyes. In both cases, ocular examination revealed follicular conjunctivitis and blepharitis in both eyes, and corneal sterile infiltration with neovascularization in the left eyes. The three topical drugs were discontinued and replaced with 0.1% fluorometholone. Both the blepharitis and corneal sterile infiltration improved thereafter, although corneal opacity remained across the stromal layer.. We encountered two cases of corneal and conjunctival complications that were suspected as side effects after brimonidine eye drop use. Special care should be taken to observe the condition of ocular surface when topical brimonidine is administered.

Topics: Aged; Antihypertensive Agents; Bimatoprost; Blepharitis; Brimonidine Tartrate; Conjunctivitis; Corneal Neovascularization; Corneal Opacity; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Low Tension Glaucoma; Male; Ophthalmic Solutions; Sulfonamides; Thiazines; Thiophenes

This study was carried out to evaluate the drug prescribing, utilization pattern and adverse drug reactions recording associated with drugs prescribed to glaucoma patients.. A total of 50 glaucoma patients were included in the study, based on inclusion and exclusion criteria. All the observations were recorded in drug utilization and ADR recording documentation form.. Out of 50 patients suffering from glaucoma, 38 patients (76%) were diagnosed open angle glaucoma, 4 patients (8%) closed angle glaucoma and 8 patients (16%) post-operative respectively. There were 19 patients (38%) males and 31 patients (62%) were females. The age range between 41-50 years had the maximum number of patients 15 (30%). A total of 17 patients (34%) had family history of glaucoma. Timolol was prescribed to 34 patients (68%), followed by dorzolamide 18 patients (36%) and acetazolamide 14 patients (28%). A total of 32 patients (64%) were prescribed single drug therapy whereas 18 patients (36%) were on multiple drug therapy. A total of 25 patients (50%) reported ADR. In the present study, latanoprost was associated with maximum number of ADRs 9 patients (18%) followed by acetazolamide 7 patients (14%), dorzolamide 4 patients (8%), then timolol 3 patients (6%) and pilocarpine 2 patients (4%). According to Naranjo scale, in 6 patients (24%) the ADR were unlikely, 12 patients (48%) were given possible score, 3 patients (12%) were given probable score, and 4 patients (16%) were given definite scores.. In the present study, the maximum patients were in the age group of 41-50 years. The most commonly prescribed drugs were timolol followed by dorzolamide, acetazolamide. Latanoprost was associated with maximum number of ADRs.

Topics: Acetazolamide; Adult; Adverse Drug Reaction Reporting Systems; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Drug-Related Side Effects and Adverse Reactions; Female; Glaucoma; Hospitals, University; Humans; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Timolol

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Models, Biological; Predictive Value of Tests

The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.

Topics: Adverse Drug Reaction Reporting Systems; Artificial Intelligence; Computers; Databases, Factual; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Models, Molecular; Quantitative Structure-Activity Relationship; Software; United States; United States Food and Drug Administration