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Biomedical subjects

N H Shear

Publications and source records attributed to N H Shear.

At least 91 records · Page 5Linked to original sources
PubMed1997

Drug interactions in human neuropathic pain pharmacotherapy.

Current practice predicates the use of multiple drug combinations in the treatment of neuropathic pain. These combinations may be required because of multiple pain symptoms directly arising from neuropathic pathology, other symptoms attributable to the chronicity and severity of the patient's pain or conditions unrelated to their pain. A fear exists that combination drug use or the addition of a new drug to a therapeutic regimen may lead to increased drug toxicity or decreased efficacy. Many of the drug interactions of significance to neuropathic pain physicians involve the cytochromes P450 2D6 and 3A3/4 isoenzymes. Drug interactions should be more predictable based on the knowledge of which compounds induce, inhibit or are metabolized by specific cytochrome P450 enzymes. Mechanisms of induction or inhibition of biotransformation via the P450 hepatic enzyme system are discussed and various inducers, inhibitors and substrates relating to neuropathic pain pharmacotherapy are listed.

Analgesics↗
PubMed1997

Serious dermatologic reactions in children.

Although serious reactions comprise only a small percentage of total adverse drug reactions, they are important in terms of morbidity and potential mortality. An update on serious dermatologic reactions in children is presented including serum sickness-like reactions due to cefaclor, hypersensitivity syndrome reactions (HSRs), and drug-induced pseudoporphyria. More detailed information on minocycline-induced reactions including drug-induced lupus and HSRs and lamotrigine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome will be discussed.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Seasonal prevalence of vitamin D deficiency in institutionalized older adults.

OBJECTIVE: To determine the prevalence and seasonal variation of vitamin D deficiency among older residents of long-term care facilities. DESIGN: Cross-sectional survey with 6-month follow-up. SETTING: Three long-term care facilities in Toronto. PATIENTS: Persons more than 65 years old, medically stable, who had resided in the facility for at least 6 months and had no conditions known to interfere with vitamin D metabolism. MEASUREMENTS: Information regarding demographics, past health, and medication use was collected. Mental and functional status were assessed by questionnaire. Venous blood samples were analyzed for alkaline phosphatase, calcium profile, albumin, intact parathyroid hormone, 25 hydroxyvitamin D (25OHD), and vitamin D binding protein in September 1994 and March 1995. In a subgroup of patients, bone specific alkaline phosphatase was measured, and dietary intake of vitamin D was assessed. RESULTS: A total of 155 subjects completed the study. The mean age of the subjects was 83.2 years (SD 7.1), and 47% were female. The mean 25OHD level in the March sample (39.9 nmol/L, SD 19.7) was significantly lower than the mean 25OHD level in the September sample (44.9 nmol/L, SD 16.9) (P = .001). The prevalence of vitamin D deficiency in the osteomalacic range (25OHD < 25 nmol/L) increased from 9% in the fall sample to 18% after the winter (chi 2 = 4.65, P = .03). The prevalence of borderline deficiency or hypovitaminosis D (25OHD < 40 nmol/L) increased from 38% in the fall sample to 60% in the spring sample (chi 2 = 14.9, P < .001). Dependence in transfers was associated with an increased risk of hypovitaminosis D, odds ratio 2.08 (95% confidence interval 1.08-4.01), dependence in ambulation 2.57 (1.26-5.23), and regular use of a wheelchair 2.17 (1.09-4.31). When entered into a forward conditional logistic regression model, only dependence in ambulation remained significant, with an adjusted odds ratio of 2.57 (95% CI: 1.26-5.18). CONCLUSIONS: Vitamin D deficiency and borderline vitamin D status are common among older residents of long-term care facilities in Canada. Even though this population has limited outdoor exposure, seasonal variation in the prevalence of deficiency remains significant. Evaluation of interventions to improve the status of vitamin D nutrition in this population is needed.

Aged↗
PubMed1997

Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Antitubercular Agents↗
PubMed1997

Onychomycosis. Going for cure.

OBJECTIVE: To review onychomycosis with an emphasis on the traditional and newer antifungal agents available to treat onychomycosis. QUALITY OF EVIDENCE: We searched MEDLINE for the years 1966 to 1995. We excluded case reports from our analysis. MAIN FINDINGS: For treating onychomycosis, newer antifungal agents (such as terbinafine, itraconazole, and fluconazole) are more cost-effective than the traditional agents griseofulvin and ketoconazole. Of the newer agents, only terbinafine is currently approved in Canada for treating onychomycosis. CONCLUSIONS: The new generation of drugs is an important addition to the armamentarium of therapies available for treating onychomycosis. At the moment, in Canada, terbinafine is the drug of choice and more cost-effective than griseofulvin for treating dermatophyte-induced onychomycosis.

Algorithms↗
PubMed1997

Comparative safety of tetracycline, minocycline, and doxycycline.

BACKGROUND: Because minocycline can cause serious adverse events including hypersensitivity syndrome reaction (HSR), serum sicknesslike reaction (SSLR), and drug-induced lupus, a follow-up study based on a retrospective review of our Drug Safety Clinic and the Health Protection Branch databases and a literature review was conducted to determine if similar rare events are associated with tetracycline and doxycycline. Cases of isolated single organ dysfunction (SOD) attributable to the use of these antibiotics also were identified. OBSERVATIONS: Nineteen cases of HSR due to minocycline, 2 due to tetracycline, and 1 due to doxycycline were identified. Eleven cases of SSLR due to minocycline, 3 due to tetracycline, and 2 due to doxycycline were identified. All 33 cases of drug-induced lupus were attributable to minocycline. Forty cases of SOD from minocycline, 37 cases from tetracycline, and 6 from doxycycline were detected. Hypersensitivity syndrome reaction, SSLR, and SOD occur on average within 4 weeks of therapy, whereas minocycline-induced lupus occurs on average 2 years after the initiation of therapy. CONCLUSIONS: Early serious events occurring during the course of tetracycline antibiotic treatment include HSR, SSLR, and SOD. Drug-induced lupus, which occurs late in the course of therapy, is reported only with minocycline. We theorize that minocycline metabolism may account for the increased frequency of serious adverse events with this drug.

Adolescent↗
PubMed1996

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports.

OBJECTIVE: To review reported cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with the use of selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES: A search of MEDLINE for reports of hyponatremia and SIADH associated with the use of fluoxetine, fluvoxamine, paroxetine or sertraline published between January 1980 and May 1995. Unpublished reports of cases were requested from the pharmaceutical industry, the Ontario Medical Association, the Health Protection Branch of Health Canada, the US Food and Drug Administration and the World Health Organization. DATA SELECTION AND EXTRACTION: Spontaneous reports from postmarketing surveillance. DATA SYNTHESIS: A total of 736 cases of hyponatremia [corrected] and SIADH associated with SSRI use were reported. Fluoxetine was involved in 554 (75.3%) of the cases, paroxetine in 91 (12.4%), sertraline in 86 (11.7%) and fluvoxamine in 11 (1.5%). Reports of 30 cases were published. The remaining 706 cases were reported to monitoring bodies and the pharmaceutical industry. According to information in the published reports, the median time to onset of hyponatremia was 13 days (range 3 to 120 days). Most (83%) of the published cases involved patients 65 years of age or more, as compared with 74% of the unpublished cases. CONCLUSION: Elderly people may be at increased risk for hyponatremia associated with SSRI use. Physicians caring for elderly patients should be aware of this potentially serious but reversible adverse effect. Further research is required to determine the incidence of this adverse effect, the relative risk of hyponatremia and SIADH in different age groups and the risk associated with different SSRI drugs.

1-Naphthylamine↗
PubMed1996

Dapsone in prevention of recurrent neutrophilic eccrine hidradenitis.

Neutrophilic eccrine hidradenitis has been described in patients with acute myelogenous leukemia and other malignant diseases, usually during chemotherapy. We describe a 46-year-old man with Hodgkin's disease in whom neutrophilic eccrine hidradenitis developed after each of the first two treatments with lomustine. Dapsone, 100 mg daily, was initiated 48 hours before the patient's third treatment with lomustine and was continued for 14 days. This regimen was successful in suppressing the reaction during the first course and three subsequent courses of lomustine.

Antineoplastic Agents↗
PubMed1996

Dapsone hypersensitivity syndrome.

We describe a 22-year-old woman with cutaneous polyarteritis nodosa in whom dapsone hypersensitivity syndrome (DHS) developed 5 weeks after initiation of dapsone therapy. She had fever and cervical lymphadenopathy, and later a widespread erythematous eruption studded with pustules developed. She also had liver involvement with mixed hepatocellular and cholestatic features. The patient was treated with prednisone 60 mg daily. Once the patient's liver function normalized, prednisone dosage was reduced by 5 mg weekly. The clinical features and treatment of DHS are reviewed. We encourage immediate discontinuation of the drug in a patient in whom a fever or flu-like illness develops, especially 4 or more weeks after the treatment is started. We also suggest routine thyroid function testing 3 months after recovery because of the possible risk of hypothyroidism.

Administration, Oral↗
PubMed1996

Mechanisms of drug reactions: the metabolic track.

Hypersensitivity syndrome (HSR) describes a drug-induced symptom complex consisting of fever, rash, and internal organ involvement. Although these reactions are rare, they are very important because of their severity and unpredictability. The metabolic conversion of drugs to chemically-reactive products is now established as a prerequisite for many idiosyncratic drug reactions. In the setting of HSR, an imbalance in the rates of formation of reactive metabolites and of enzymatic detoxification can lead to accumulation of these byproducts. Reactive metabolites could act as haptens eliciting an immune response, covalently bind target proteins causing cell death, or interact with nucleic acids leading to mutations. The lymphocyte toxicity assay (LTA) provides an in vitro assessment of host susceptibility to reactive metabolites of a given drug. It has validated the clinical finding of increased risk of HSR in first degree relatives of patients. It is hoped that the LTA will be used to predict host susceptibility before drug exposure. Ultimately it is hoped that the genetic defects that lead to drug reactions will be identified. This would improve drug development safety and allow primary prevention of serious reactions.

Anticonvulsants↗
PubMed1996

Clinical and economic factors in the treatment of onychomycosis.

Onychomycosis is a fungal infection of fingernails and toenails, most cases of which are caused by dermatophytes. The disease accounts for 15% of all nail disease, and affects approximately 2 to 3% of people of all ages and both sexes. Topical treatment with tioconazole, amorolfine or ciclopirox has limited effectiveness. Oral griseofulvin 500 to 1000mg daily has been the mainstay of treatment, but prolonged therapy is required and success rates are low. Therapy with itraconazole 200mg daily for 3 to 6 months is more effective (70 to 85% success), although so-called 'pulse' therapy has shown similar success with potentially fewer adverse effects. Terbinafine 250mg daily produces clinical and mycological cure in approximately 80% of patients treated for 6 and 12 weeks for fingernail and toenail infections, respectively. The overall costs of treating onychomycosis are substantial, and it has been estimated that direct costs for Medicare patients with the disease were $US43 million in 1 year. In addition, the disease has a negative impact on quality of life, in the domains of mental functioning, health concern, social functioning, and physical appearance. Few pharmacoeconomic analyses have been published, but all have indicated an advantage of oral terbinafine over griseofulvin and other oral agents. To date, no economic studies have been performed on topical agents, pulse therapy or combination treatments.

Animals↗
PubMed1996

Serious adverse reactions induced by minocycline. Report of 13 patients and review of the literature.

BACKGROUND: Minocycline has been reported to cause serious, albeit rare, adverse events, including serum sickness-like reaction, hypersensitivity syndrome reaction, and drug-induced lupus. A retrospective review of patients seen in our Adverse Drug Reaction Clinic as well as information obtained from the Health Protection Branch was done to identify patients with minocycline-induced reactions. In addition, the literature concerning serious reactions to minocycline was reviewed. OBSERVATIONS: Six patients with a hypersensitivity syndrome reaction, 6 patients with a serum sickness-like reaction, and 1 patient who had symptoms consistent with drug-induced lupus were identified. A review of the literature identified 11 cases of hypersensitivity syndrome reaction, 1 case of serum sickness-like reaction, and 24 cases of drug-induced lupus. Serum sickness-like reactions occur sooner than hypersensitivity syndrome reactions (15.6 vs 23.7 days, P = .04). Drug-induced lupus occurs on average 2 years after the start of minocycline therapy. CONCLUSIONS: Dermatologists need to be aware of the serious adverse reactions that can develop after minocycline use. In patients who may require long-term therapy with minocycline ( > 1 year), we suggest that antinuclear antibody and hepatic transaminase levels be determined at baseline. Rechallenge with minocycline or other tetracyclines is currently not recommended for patients who develop these serious reactions.

Adolescent↗