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1.
J Vet Intern Med ; 35(2): 1121-1130, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33656183

RESUMO

BACKGROUND: Gastrointestinal (GI) injury and dysbiosis are adverse events associated with nonsteroidal anti-inflammatory drug (NSAID) use in horses. Phenylbutazone has been shown to alter GI barrier function both in vitro and ex vivo, but its effects on barrier function have not been assessed in vivo. In addition, the ability of nutritional therapeutics to prevent these changes is not known. OBJECTIVE: Our objectives were to determine whether (a) phenylbutazone affected barrier function in vivo and (b) if phenylbutazone-induced GI injury could be ameliorated by the use of a nutritional therapeutic. ANIMALS: Thirty healthy horses were randomly assigned to 3 groups (n = 10 per group): control, phenylbutazone, or phenylbutazone plus nutritional therapeutic. METHODS: This study was conducted as a blinded, randomized block design. All horses were managed identically throughout the study period. Samples were collected throughout the study period to monitor fecal microbiota changes and gastric ulcers before and after treatment. Quantification of the bacterial 16S rRNA gene in blood was used as a marker of intestinal permeability. RESULTS: Phenylbutazone increased amounts of bacterial 16S rDNA in circulation 3.02-fold (95% confidence interval [CI], 0.1.89-4.17), increased gastric ulceration score by a mean of 1.1 grade (P = .02), and induced specific changes in the microbiota, including loss of Pseudobutyrivibrio of family Lachnospiraceae. These changes were attenuated by nutritional treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Collectively, these findings suggest that phenylbutazone induces GI injury, including impaired barrier function, and that nutritional treatment could attenuate these changes.


Assuntos
Doenças dos Cavalos , Microbiota , Úlcera Gástrica , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Permeabilidade , Fenilbutazona/efeitos adversos , RNA Ribossômico 16S/genética , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/veterinária
2.
Equine Vet J ; 53(2): 356-363, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32697849

RESUMO

BACKGROUND: Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. OBJECTIVES: To evaluate the effect of omeprazole on phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). STUDY DESIGN: Randomised block experimental design. METHODS: Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. RESULTS: EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. MAIN LIMITATIONS: Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications. CONCLUSIONS: Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.


Assuntos
Doenças dos Cavalos , Úlcera Gástrica , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Omeprazol/efeitos adversos , Fenilbutazona/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/veterinária
3.
J Am Vet Med Assoc ; 257(6): 642-647, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32856998

RESUMO

OBJECTIVE: To examine the association between prerace administration of phenylbutazone and the risk of musculoskeletal injury (MSI) and fatal injury in Thoroughbred racehorses that raced between 2006 and 2015 at 2 of the 4 official racetracks in Argentina. SAMPLE: Data from racetrack databases and veterinary reports on 283,193 race starts. PROCEDURES: Data were collected relating to race performance and injury outcomes for starts at these tracks. The incidence of MSI and fatal injury was calculated for each year, stratified by the declared prerace administration of phenylbutazone. Univariable logistic regression, followed by multivariable logistic regression, was used to identify significant risk factors for both MSI and fatal injury. RESULTS: Analyses identified associations between the declared prerace administration of phenylbutazone and the risk of MSI and fatal injury during racing. Horses with declared prerace phenylbutazone administration had greater odds of MSI (OR, 1.45 [95% CI, 1.03 to 2.04]) and fatal injury (OR, 1.59 [95% CI, 1.1 to 2.27]) than did horses racing without prerace phenylbutazone administration. These associations remained significant when other risk factors were accounted for in both multivariable models. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested an association between the prerace administration of phenylbutazone and the risk of MSI and fatal injury in Thoroughbred racehorses during racing. Although these results did not imply a direct causal relationship between prerace phenylbutazone administration and injury, they may be considered in the development of more conservative medication policies to optimize racehorse welfare in North and Latin America.


Assuntos
Fenilbutazona , Animais , Argentina/epidemiologia , Cavalos , Incidência , Modelos Logísticos , Fenilbutazona/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
4.
Molecules ; 24(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609687

RESUMO

A drug design for safer phenylbutazone was been explored by reactivity and docking studies involving single electron transfer mechanism, as well as toxicological predictions. Several approaches about its structural properties were performed through quantum chemistry calculations at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and ionization potential were associated to electron donation capacity. The spin densities contribution showed a preferential hydroxylation at the para-positions of phenyl ring when compared to other positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than alkyl hydroxylation. Docking studies indicate that six structures 1, 7, 8 and 13⁻15 have potential for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed are potentially more active as well safer than phenylbutazone and only structures 8 and 13⁻15 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.


Assuntos
Fenilbutazona/química , Fenilbutazona/farmacologia , Descoberta de Drogas/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fenilbutazona/efeitos adversos , Fenilbutazona/toxicidade , Relação Estrutura-Atividade
5.
PLoS One ; 13(8): e0202527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30138339

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in both veterinary and human medicine. Gastrointestinal injury is a frequent adverse event associated with NSAID use and evidence suggests that NSAIDs induce gastrointestinal microbial imbalance (i.e., dysbiosis) in both animals and people. It is unknown, however, whether cyclooxygenase (COX)-2-selective NSAIDs induce dysbiosis, or if this phenomenon occurs in horses administered any class of NSAIDs. Therefore, our objectives were to determine whether the composition and diversity of the fecal microbiota of adult horses were altered by NSAID use, and whether these effects differed between non-selective and COX-2-selective NSAIDs. Twenty-five adult horses were randomly assigned to 1 of 3 groups: control (n = 5); phenylbutazone (n = 10); or, firocoxib (n = 10). Treatments were administered for 10 days. Fecal samples were collected every 5 days for 25 days. DNA was extracted from feces and the 16S rRNA gene amplified and sequenced to determine the composition of the microbiota and the inferred metagenome. While the fecal microbiota profile of the control group remained stable over time, the phenylbutazone and firocoxib groups had decreased diversity, and alteration of their microbiota profiles was most pronounced at day 10. Similarly, there were clear alterations of the inferred metagenome at day 10 compared to all other days, indicating that use of both non-selective and selective COX inhibitors resulted in temporary alterations of the fecal microbiota and inferred metagenome. Dysbiosis associated with NSAID administration is clinically relevant because dysbiosis has been associated with several important diseases of horses including abdominal pain (colic), colitis, enteric infections, and laminitis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Microbiota/efeitos dos fármacos , RNA Ribossômico 16S/genética , 4-Butirolactona/administração & dosagem , 4-Butirolactona/efeitos adversos , 4-Butirolactona/análogos & derivados , Adulto , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Fezes/microbiologia , Cavalos/microbiologia , Humanos , Metagenoma/efeitos dos fármacos , Fenilbutazona/administração & dosagem , Fenilbutazona/efeitos adversos , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos
6.
J Vet Pharmacol Ther ; 41(2): 239-245, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29148168

RESUMO

In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups. Before treatment and 3 and 7 days after initiation of treatment, gastroscopy was performed and glandular gastric biopsies were collected and frozen at -80°C. Glandular disease was assessed on a scale of 0-4. Prostaglandin E2 concentrations in biopsies were measured using a commercially available enzyme-linked immunosorbent assay. All phenylbutazone-treated horses developed grade ≥2 glandular disease. Prostaglandin concentrations increased over time (p = .0017), but there was no effect of treatment (p = .49). These findings indicate that despite induction of glandular disease grade ≥2, phenylbutazone did not decrease basal glandular gastric prostaglandin E2 concentration.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dinoprostona/análise , Mucosa Gástrica/química , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/efeitos adversos , Gastropatias/veterinária , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Mucosa Gástrica/patologia , Gastroscopia/veterinária , Doenças dos Cavalos/patologia , Cavalos , Gastropatias/induzido quimicamente , Gastropatias/metabolismo , Gastropatias/patologia
8.
PLoS One ; 10(10): e0141419, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26512724

RESUMO

The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN) and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac and ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species. The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or pathological lesions were noted following exposure. Clinical signs of lethargy and depression were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within the population reference interval in contrast to the effects previously described for diclofenac and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological changes and/or long half-lives of elimination suggests that all three drugs have a potential for toxicity in a larger population or on repeat administration. In conclusion while the studied substances were not as overtly toxic as diclofenac, they are of safety concern.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carbazóis/farmacologia , Clonixina/análogos & derivados , Falconiformes , Fenilbutazona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacocinética , Biomarcadores , Carbazóis/administração & dosagem , Carbazóis/efeitos adversos , Carbazóis/farmacocinética , Clonixina/administração & dosagem , Clonixina/efeitos adversos , Clonixina/farmacocinética , Clonixina/farmacologia , Testes de Função Hepática , Fenilbutazona/administração & dosagem , Fenilbutazona/efeitos adversos , Fenilbutazona/farmacocinética
9.
J Vet Pharmacol Ther ; 38(3): 257-64, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25287371

RESUMO

Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti-inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide dismutase, SOD; catalase, CAT; nitric oxide, NO; total glutathione, GSH; myeloperoxidase, MPO; and malondialdehyde, MDA), PGE2 levels, and the ulcerative lesions score were assessed. The results demonstrated decreased levels of antioxidant variables, increased levels of oxidant variables, and alterations in the prostaglandin E2 (PGE2 ), myeloperoxidase (MPO), and glutathione (GSH) levels. In conclusion, PBZ induces oxidative stress in the gastric glandular mucosa of horses by changing the antioxidant-oxidant balance of this surface, which might be regarded as another mechanism of injury in the horse stomach.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenilbutazona/efeitos adversos , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Catalase/análise , Dinoprostona/análise , Feminino , Mucosa Gástrica/química , Mucosa Gástrica/metabolismo , Gastroscopia/veterinária , Glutationa/análise , Doenças dos Cavalos/induzido quimicamente , Cavalos , Masculino , Malondialdeído/análise , Óxido Nítrico/análise , Peroxidase/análise , Fenilbutazona/administração & dosagem , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/análise
10.
PLoS One ; 9(3): e91874, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24626481

RESUMO

Previously we have developed a transgenic zebrafish line (LiPan) with liver-specific red fluorescent protein (DsRed) expression under the fabp10a promoter. Since red fluorescence in the liver greatly facilitates the observation of liver in live LiPan fry, we envision that the LiPan zebrafish may provide a useful tool in analyses of hepatotoxicity based on changes of liver red fluorescence intensity and size. In this study, we first tested four well-established hepatotoxins (acetaminophen, aspirin, isoniazid and phenylbutazone) in LiPan fry and demonstrated that these hepatotoxins could significantly reduce both liver red fluorescence and liver size in a dosage-dependent manner, thus the two measurable parameters could be used as indicators of hepatotoxicity. We then tested the LiPan fry with nine other chemicals including environmental toxicants and human drugs. Three (mefenamic acid, lindane, and arsenate) behave like hepatotoxins in reduction of liver red fluorescence, while three others (17ß-estradiol, TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] and NDMA [N-nitrosodimethylamine]) caused increase of liver red fluorescence and the liver size. Ethanol and two other chemicals, amoxicillin (antibiotics) and chlorphenamine (pain killer) did not resulted in significant changes of liver red fluorescence and liver size. By quantitative RT-PCR analysis, we found that the changes of red fluorescence intensity caused by different chemicals correlated to the changes of endogenous fabp10a RNA expression, indicating that the measured hepatotoxicity was related to fatty acid transportation and metabolism. Finally we tested a mixture of four hepatotoxins and observed a significant reduction of red fluorescence in the liver at concentrations below the lowest effective concentrations of individual hepatotoxins, suggesting that the transgenic zebrafish assay is capable of reporting compound hepatotoxicity effect from chemical mixtures. Thus, the LiPan transgenic fry provide a rapid and convenient in vivo hepatotoxicity assay that should be applicable to high-throughput hepatotoxicity test in drug screening as well as in biomonitoring environmental toxicants.


Assuntos
Fígado/efeitos dos fármacos , Proteínas Luminescentes/biossíntese , Peixe-Zebra/genética , Acetaminofen/efeitos adversos , Animais , Animais Geneticamente Modificados/genética , Aspirina/efeitos adversos , Substâncias Perigosas/farmacologia , Humanos , Isoniazida/efeitos adversos , Fígado/patologia , Proteínas Luminescentes/genética , Fenilbutazona/efeitos adversos
11.
J Vet Pharmacol Ther ; 37(4): 413-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24354928

RESUMO

Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10-day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine-specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co-administration of phenylbutazone and firocoxib may cause renal disease.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças dos Cavalos/induzido quimicamente , Nefropatias/veterinária , Fenilbutazona/efeitos adversos , Sulfonas/efeitos adversos , 4-Butirolactona/administração & dosagem , 4-Butirolactona/efeitos adversos , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Proteínas Sanguíneas , Creatinina/sangue , Quimioterapia Combinada , Doenças dos Cavalos/sangue , Cavalos , Nefropatias/induzido quimicamente , Fenilbutazona/administração & dosagem , Prostaglandina-Endoperóxido Sintases/metabolismo , Sulfonas/administração & dosagem
13.
Ann Pharmacother ; 46(12): 1688-99, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23249870

RESUMO

OBJECTIVE: To review the current literature on drug-induced parotitis. DATA SOURCES: Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. DATA SYNTHESIS: Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. CONCLUSIONS: Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other drugs have been implicated in the development of parotitis; however, the evidence supporting this association is insufficient to determine causality at this time.


Assuntos
Parotidite/induzido quimicamente , Sialadenite/induzido quimicamente , Asparaginase/efeitos adversos , Clozapina/efeitos adversos , Humanos , Parotidite/diagnóstico , Parotidite/patologia , Fenilbutazona/efeitos adversos , Sialadenite/patologia
14.
J Am Vet Med Assoc ; 239(4): 499-503, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21838588

RESUMO

CASE DESCRIPTION: A 15-year-old Quarter Horse gelding and a 26-year-old Thoroughbred gelding were evaluated because of hematuria of 4 to 6 days' duration following prolonged oral administration of phenylbutazone. CLINICAL FINDINGS: The horses had received either treatment with phenylbutazone for 3 months or intermittent long-term phenylbutazone treatment prior to development of hematuria. Each horse was systemically stable but had orthopedic or neurologic problems. Clinicopathologic findings included normochromic normocytic anemia in both horses and hypoalbuminemia and high BUN concentration in 1 horse. In both horses, urinalysis revealed proteinuria and RBCs, but no evidence of WBCs or bacteria. Ulceration and hemorrhage of the urinary bladder with no evidence of uroliths were observed via cystoscopy. Gastric ulceration along the margo plicatus was observed via gastroscopy. TREATMENT AND OUTCOME: For each horse, phenylbutazone treatment was discontinued and a synthetic prostaglandin (misoprostol) was administered. The hematuria resolved, and results of a follow-up CBC, serum biochemical analysis, urinalysis, and cystoscopy 25 or 30 days after cessation of phenylbutazone treatment were unremarkable in both cases. CLINICAL RELEVANCE: Given the known adverse effects of NSAID treatment in several species, phenylbutazone and its metabolites were suspected to have caused ulceration of the urinary bladder, resulting in hematuria, in the 2 horses. A definitive cause of urinary bladder ulceration was not confirmed in these cases; however, resolution of ulceration after discontinuation of phenylbutazone treatment and administration of synthetic prostaglandins and exclusion of other causes suggested an association between phenylbutazone administration and ulcerative cystitis in these horses.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Cistite/veterinária , Hematúria/veterinária , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/efeitos adversos , Animais , Antiulcerosos/uso terapêutico , Cistite/induzido quimicamente , Hematúria/induzido quimicamente , Cavalos , Masculino , Misoprostol/uso terapêutico , Omeprazol/uso terapêutico , Fenilbutazona/administração & dosagem , Fenilbutazona/uso terapêutico , Úlcera/induzido quimicamente , Úlcera/tratamento farmacológico , Úlcera/veterinária
16.
N Z Vet J ; 58(5): 224-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20927172

RESUMO

AIM: To evaluate the adverse effects of flunixin, ketoprofen and phenylbutazone when administered I/V to clinically normal miniature donkeys. METHODS: Twenty clinically normal adult (2.0-2.5 years old) male miniature donkeys weighing 113-136 kg and 0.81- 0.86 m tall were randomly assigned to one of four groups, and administered either saline (n=5), 1.0 mg/kg flunixin (n=5), 2.2 mg/kg ketoprofen (n=5), or 4.4 mg/kg phenylbutazone (n=5) I/V at 0800 hours on Day 1, then every 12 h, for 12 days. The animals were observed every 8 h, and examined physically daily. Blood, faeces and urine samples were collected daily from all donkeys, for haematological indices and enzyme activities, occult blood, and urinalysis, respectively. Immediately after euthanasia, complete post-mortem examinations were performed on all donkeys, and gross lesions recorded. Histopathology was conducted on a wide range of tissues. RESULTS: Clinically, mild anorexia and diarrhoea were observed during the study only in donkeys treated with phenylbutazone. There was an effect of treatment with the non-steroidal anti-infl ammatory drugs (NSAID) on red blood cell (RBC) counts, packed cell volume (PCV) and enzyme activities, but not on urine. Lesions were observed in the glandular mucosa of the stomach of all donkeys treated with NSAID, including ulceration in most. Also, in donkeys treated with NSAID, hyperaemia, erosion and ulceration of the gastrointestinal tract, and congestion of the liver, kidney and spleen, were observed. Microscopically, hepatic and renal lesions comprised biliary hyperplasia and interstitial nephritis, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The gastrointestinal, hepatic and renal lesions observed in the donkeys treated with NSAID demonstrated the toxic potential of NSAID, which was greatest for animals treated with phenylbutazone, less for flunixin, and least for ketoprofen. When use of these compounds is contemplated in clinical cases, the risk of adverse effects and the comparative toxic potential should be considered, together with the efficacy of the compound for the condition being treated.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Clonixina/análogos & derivados , Equidae , Cetoprofeno/efeitos adversos , Fenilbutazona/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Clonixina/administração & dosagem , Clonixina/efeitos adversos , Método Duplo-Cego , Equidae/sangue , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/veterinária , Cetoprofeno/administração & dosagem , Nefropatias/induzido quimicamente , Nefropatias/veterinária , Masculino , Fenilbutazona/administração & dosagem , Esplenopatias/induzido quimicamente , Esplenopatias/veterinária
18.
Food Chem Toxicol ; 48(5): 1270-4, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20176071

RESUMO

Sixty-seven million pounds of horsemeat derived from American horses were sent abroad for human consumption last year. Horses are not raised as food animals in the United States, and mechanisms to ensure the removal of horses treated with banned substances from the food chain are inadequate at best. Phenylbutazone (PBZ) is the most commonly used non-steroidal anti-inflammatory drug (NSAID) in equine practice. Thoroughbred (TB) race horses like other horse breeds are slaughtered for human consumption. Phenylbutazone is banned for use in any animal intended for human consumption because it causes serious and lethal idiosyncratic adverse effects in humans. The number of horses that have received phenylbutazone prior to being sent to slaughter for human consumption is unknown but its presence in some is highly likely. We identified eighteen TB race horses that were given PBZ on race day and sent for intended slaughter by matching their registered name to their race track drug record over a five year period. Sixteen rescued TB race horses were given PBZ on race day. Thus, PBZ residues may be present in some horsemeat derived from American horses. The permissive allowance of such horsemeat used for human consumption poses a serious public health risk.


Assuntos
Matadouros , Anti-Inflamatórios não Esteroides/análise , Resíduos de Drogas/análise , Contaminação de Alimentos/análise , Carne/análise , Fenilbutazona/análise , Matadouros/legislação & jurisprudência , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Qualidade de Produtos para o Consumidor , Resíduos de Drogas/efeitos adversos , Contaminação de Alimentos/legislação & jurisprudência , Cavalos , Humanos , Carne/normas , Fenilbutazona/efeitos adversos , Medição de Risco , Estados Unidos , United States Department of Agriculture/legislação & jurisprudência , United States Food and Drug Administration/legislação & jurisprudência
19.
Vet Ther ; 10(3): 113-20, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20037965

RESUMO

Eighteen mature, healthy horses were divided into three groups (six per group) receiving either no treatment, 15 consecutive days of phenylbutazone (PBZ), or 15 consecutive days of suxibuzone (SBZ) at recommended label doses. Horses underwent endoscopy before and after the treatment period and were assigned gastric ulcer scores. Gastric ulcer number and severity scores were similar across treatment groups. These findings suggest that when administered at the recommended label dose for 15 days, neither PBZ nor SBZ causes an increase in the number or severity of gastric ulcers over what would be expected with traditional stabling and intermittent feeding patterns. Also, PBZ-treated horses did not have more severe gastric ulcers than SBZ-treated horses, indicating that SBZ does not appear to offer an advantage over PBZ in preventing gastric ulcers when used at recommended label doses. However, ulcers in other regions of the gastrointestinal tract (e.g., right dorsal colon, duodenum) were not evaluated in horses in this study.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/análogos & derivados , Fenilbutazona/efeitos adversos , Úlcera Gástrica/veterinária , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Química Farmacêutica , Feminino , Doenças dos Cavalos/patologia , Cavalos , Masculino , Fenilbutazona/administração & dosagem , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
20.
J Orthop Surg (Hong Kong) ; 17(2): 223-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19721158

RESUMO

Necrotising fasciitis can be life threatening, requiring prompt diagnosis and surgical debridement. We report a case of necrotising fasciitis caused by an adulterate traditional Asian medication--Jamu Pegal Linu, containing toxic levels of phenylbutazone and dipyrone. The patient presented with severe neutropenia and sepsis. An urgent extensive debridement was carried out (within 6 hours of presentation). Repeated debridements were performed on days 2 and 5, augmented with antibiotics and granulocyte colony-stimulating factor.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dipirona/efeitos adversos , Fasciite Necrosante/induzido quimicamente , Medicina Tradicional do Leste Asiático/efeitos adversos , Fenilbutazona/efeitos adversos , Anti-Infecciosos/uso terapêutico , Desbridamento , Contaminação de Medicamentos , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/terapia , Humanos , Perna (Membro) , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
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