Francesca E. Cunningham

Effects of Remifentanil, a New Short-acting Opioid, on Cerebral Blood Flow, Brain Electrical Activity, and Intracranial Pressure in Dogs Anesthetized with Isoflurane and Nitrous Oxide

BackgroundA new short-acting opioid, remifentanil, is metabolized by esterase activity in blood and tissue. It is important to know whether remifentanil may decrease the time to recovery of opioid-induced cardiovascular and cerebral effects compared to that of other short-acting agents such as alfentanil. MethodsBaseline measures were made during 1% end-tidal isoflurane and 50% N2O in oxygen in dogs. Approximately equipotent low- and high-dose remifentanil (0.5 and 1.0

Potentially inappropriate prescribing in elderly veterans: Are we using the wrong drug, wrong dose, or wrong duration?

mUg. kg−1. min−1) or alfentanil (1.6 and 3.2

Outpatient medications and hip fractures in the US: a national veterans study.

mUg. kg−1. min−1) were infused for 30 min each (total infusion time 60 min) followed by a 30-min recovery period. Blood pressure, heart rate, and intracranial pressure were recorded continuously. Electroencephalogram measurements were made using aperiodic analysis, and regional cerebral blood flow using radioactive microspheres. ResultsBoth remifentanil and alfentanil decreased blood pressure and heart rate 25–30%. Cortex, hippocampus, and caudate blood flow decreased 40–50% during opioid infusion, but flow changes in lower brain regions were modest or absent. The electroencephalogram showed a shift from low-amplitude, high-frequency activity during baseline to high-amplitude, low-frequency activity during opioid infusion. During a 30-min recovery period, heart rate, electroencephalogram, and regional cerebral blood flow recovered to baseline levels in remifentanil- but not in alfentanil-treated dogs. Blood pressure and intracranial pressure decreased during opioid infusion and increased above baseline levels during the recovery period in remifentanil-treated dogs. ConclusionsThese results show that the cardiovascular and cerebral effects of remifentanil and alfentanil are similar but that recovery of these parameters occurs sooner following remifentanil.

Pharmacologic Management of Postdural Puncture Headache

Objectives: To identify the extent of inappropriate prescribing using criteria for proper use developed by the Agency for Healthcare Research and Quality (AHRQ) and dose‐limitation criteria defined by Beers, as well as to describe duration of use and patient characteristics associated with inappropriate prescribing for older people.

Severe Dysglycemia with the Fluoroquinolones: A Class Effect?

BackgroundCertain medications have been linked to falls. One of the most severe fall-related injuries in the elderly is a hip fracture.ObjectiveThe objective of this study was to examine the use of medications known to increase fall risk that were prescribed on an outpatient basis to veterans prior to hospital admission for hip fracture.MethodsWe identified and analysed the use of outpatient fall-related medications in 2212 unique patients with hip fractures admitted in fiscal year 2003 to Veterans Health Administration hospitals compared with that for matched controls (exact match for age and sex) admitted for acute myocardial infarction (MI) or pneumonia. We analysed the medications selected from the three drug categories most often linked with an increased risk for falls. These categories included medications that affected the cardiovascular (CVS), CNS or the musculoskeletal system (MSS). The unit of analysis was the hip fracture linked with outpatient medications in the study group compared with matched control groups of patients with hospitalisations for an acute MI or pneumonia.ResultsOf the 2212 hip-fracture patients, 70% had fall-related medications prior to hospitalisation for hip fracture. The most notable differences in usage were seen in the drug classes antiepileptics/barbiturates, antidepressants (2-fold difference in use of selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]), and antiparkinson’s drugs (nearly 4-fold difference between cases and controls). There were also notable differences in usage of antipsychotics (3-fold difference for hip-fracture cases compared with acute MI) and cholinesterase inhibitors (nearly 2-fold difference for hip-fracture cases compared with pneumonia or acute MI). The most notable differences in polypharmacy combinations were CVS and CNS categories with differences of 9.44% (absolute) and 43% (relative) for hip-fracture patients over acute MI, and 4.83% (absolute) and 18% (relative) for hip-fracture patients over pneumonia patients.ConclusionsThis is the first national Veterans Health Administration hip fracture hospitalisation study that temporally linked outpatient fall-related medications in hip-fracture patients with matched controls. We found that of veterans with hip-fracture hospitalisations, 70% were prescribed outpatient medications from selected major drug categories that may potentially increase fall risk. Moreover, over one-third of hip-fracture patients received concomitant prescriptions of drugs from multiple selected drug categories. Hip-fracture patients, compared with matched controls of acute MI and pneumonia, had the largest pronounced differences in prescribed medications in the antiepileptics, antidepressants, antipsychotics and antiparkinson’s drug classes. Although a randomised clinical trial is the ‘gold standard’ for determining causation issues, exposing patients, particularly the elderly, to the potential risk of injurious falls would raise serious patient safety research approval issues. If the relationship between selected drugs and falls is indeed to some extent causative, future retrospective multivariate analyses could quantify the magnitude of these effects.

Pharmacokinetics of Intravaginal Metronidazole Gel

OBJECTIVE: To discuss the pathogenesis, incidence, and clinical presentation of postdural puncture headaches (PDPHs) and to provide a comprehensive evaluation on the pharmacologic management of PDPH. DATA SOURCE: A MEDLINE search was used to identify pertinent literature published in English including review articles, case reports, letters, and abstracts. Information was also extracted from textbooks for background purposes. STUDY SELECTION: All clinical studies, case reports, abstracts, and letters were included because of the limited amount of literature available on the pharmacologic therapy for PDPH. Related research articles and review articles were also used to provide background information on PDPH. DATA EXTRACTION: Methodology and results from clinical trials and abstracts were described and evaluated. Case reports and letters were summarized and critically reviewed for the feasibility of the different treatment modalities. Information on the pathophysiology, incidence and severity, and clinical presentation of PDPH was extracted from related research articles, review articles, and textbooks. DATA SYNTHESIS: The epidural blood patch (EBP) is one of the most effective treatments for PDPH. Pharmacologic management of PDPH offers a less invasive treatment modality than the EBP. Numerous drug therapies have been presented in the literature, though few merit clinical application. Caffeine therapy, both oral and parenteral, is the most commonly used pharmacologic treatment modality. Theophylline and sumatriptan are potentially promising agents for the treatment of PDPH. Epidural administration of fluids and drugs is also effective in the treatment of PDPH. Epidural administration of NaCl 0.9% and dextran may be an alternative to the EBP when the EBP is unsuccessful or contraindicated. Epidural adrenocorticotropic hormone and epidural morphine also demonstrate some potential in the treatment of PDPH. Individual patient characteristics (i.e., HIV, sepsis) need to be considered when deciding on a treatment. More reports, especially clinical studies, are necessary before a definitive statement can be made regarding any one treatment. In the meantime, therapy will be guided by clinical judgment based on the literature reviewed in this article. CONCLUSIONS: Intravenous and oral caffeine are effective and noninvasive treatments for PDPH. Epidural NaCl 0.9% or dextran are alternatives when the EBP is unsuccessful or contraindicated. Several methods of pharmacologic management have been cited in the literature, but all require further evaluation.

Potentially inappropriate prescribing for the elderly: Effects of geriatric care at the patient and health care system level

BACKGROUND Although gatifloxacin is no longer available, other fluoroquinolones may significantly interfere with glucose homeostasis. The objective of the present study was to compare the risk of severe hypo- and hyperglycemia in a cohort of patients treated with gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin. METHODS This was a retrospective inception cohort study of outpatients with a new prescription for gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin from 1 October 2000 through 30 September 2005 in the Veterans Affairs health care system. For patients who received one of these antibiotics, we identified outcomes of hospitalization with a primary diagnosis of hypo- or hyperglycemia. Multivariable logistic regression was used to determine the odds of hypo- and hyperglycemia with the individual fluoroquinolones versus azithromycin. RESULTS The crude incidence rates for severe hypo- and hyperglycemia among those who received gatifloxacin, levofloxacin, ciprofloxacin, and azithromycin were 0.35 and 0.45, 0.19 and 0.18, 0.10 and 0.12, and 0.07 and 0.10 cases per 1000 patients, respectively. Among patients with diabetes, the odds ratios for hypoglycemia compared with azithromycin were 4.3 (95% confidence interval [CI], 2.7-6.6) for gatifloxacin, 2.1 (95% CI, 1.4-3.3) for levofloxacin, and 1.1 (95% CI, 0.6-2.0) for ciprofloxacin. The odds ratios for hyperglycemia were 4.5 (95% CI, 3.0-6.9) for gatifloxacin, 1.8 (95% CI, 1.2-2.7) for levofloxacin, and 1.0 (95% CI, 0.6-1.8) for ciprofloxacin. CONCLUSIONS The odds of severe hypo- and hyperglycemia were significantly greater with gatifloxacin and levofloxacin, but not ciprofloxacin, than with azithromycin. Thus, the risk of a clinically relevant dysglycemic event appears to vary among the fluoroquinolones.

Patient characteristics and prescription patterns of atypical antipsychotics among patients with schizophrenia

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48‐hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500‐mg oral dose. The dose‐adjusted maximum serum concentration (898 ± 121 ng/mL vs. 237 ± 69 ng/mL) and area under the serum concentration—time curve (9362 ± 2873 ng * hr/mL vs. 4977 ± 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 ± 0.6 hr vs. 8.4 ± 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis.

Effect of increased copayments on pharmacy use in the Department of Veterans Affairs

Background:Many studies have identified patient characteristics associated with potentially inappropriate prescribing in the elderly (PIPE), however, little attention has been directed toward how health care system factors such as geriatric care may affect this patient safety issue. Objective:This study examines the association between geriatric care and PIPE in a community dwelling elderly population. Research Design:Cross-sectional retrospective database study. Subjects:Veterans age ≥65 years who received health care in the VA system during Fiscal Years (FY99-00), and also received at medications from the Veterans Administration in FY00. Measures:PIPE was identified using the Zhan adaptation of the Beers criteria. Geriatric care penetration was calculated as the proportion of patients within a facility who received at least 1 geriatric outpatient clinic or inpatient visit. Analyses:Logistic regression models with generalized estimating equations were used to assess the relationship between geriatric care and PIPE after controlling for patient and health care system characteristics. Results:Patients receiving geriatric care were less likely to have PIPE exposure (odds ratio, 0.64; 95% confidence interval, 0.59–0.73). There was also a weak effect for geriatric care penetration, with a trend for patients in low geriatric care penetration facilities having higher risk for PIPE regardless of individual geriatric care exposure (odds ratio, 1.14; 95% confidence interval, 0.99–1.30). Conclusions:Although geriatric care is associated with a lower risk of PIPE, additional research is needed to determine if heterogeneity in the organization and delivery of geriatric care resulted in the weak effect of geriatric care penetration, or whether this is a result of low power.

Provision of potentially teratogenic medications to female veterans of childbearing age.

Background:  Schizophrenia, one of the leading causes of disability, contributes substantially to the use of medical and mental health services. The treatment of schizophrenia is therefore particularly important to reduce deficits across a large number of neurocognitive domains.