Prescription drug misuse/abuse in the elderly.

One quarter of the prescription drugs sold in the United States are used by the elderly, often for problems such as chronic pain, insomnia, and anxiety. The prevalence of abuse may be as high as 11 percent with female gender, social isolation, depression, and history of substance abuse increasing risk. Screening instruments for prescription drug abuse have not been validated in the geriatric population. Benzodiazepines, opiate analgesics, and some skeletal muscle relaxants may result in physical dependence; however, tolerance, withdrawal syndrome, and dose escalation may be less common in the older patient. Lower doses may decrease the risk of abuse and dependence; however, fear of abuse often results in a failure to adequately treat symptoms such as anxiety, pain, and insomnia.

Potential in vitro interaction between tenecteplase and unfractionated heparin.

STUDY OBJECTIVE: To explore the potential of a direct drug interaction between unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic propensity of UFH to prolong the activated partial thromboplastin time (aPTT). DESIGN: In vitro experiment. SETTING: Texas Tech University School of Pharmacy, with sample analysis performed at an independent, contract laboratory. Samples. Blood samples collected from healthy volunteers. INTERVENTION: Three separate in vitro experiments were conducted to explore the relative influence of various thrombolytic agents with and without UFH on aPTT prolongation. In each experiment, blood from healthy volunteers (12 for each experiment) was treated with different concentrations and combinations of tenecteplase and UFH. MEASUREMENTS AND MAIN RESULTS: When the effects of tenecteplase plus UFH versus UFH alone on aPTT prolongation were compared, each experiment demonstrated attenuation of aPTT with the combination versus UFH alone. In contrast, findings for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT compared with UFH alone. CONCLUSION: The results indicate a possible drug interaction between tenecteplase and UFH, with tenecteplase attenuating the intensity of anticoagulation of UFH in vitro. Further investigation into this possible interaction is warranted in the clinical setting.

Comparison of effects of quinapril versus enalapril on vasoactive substances following acute myocardial infarction.

The true existence of a class effect in angiotensin-converting enzyme (ACE) inhibitors remains controversial. The present trial explored the effects of 2 ACE inhibitors after acute myocardial infarction and found no difference in endothelin-1 production but a greater increase in the production of total nitric oxide with quinapril than with enalapril.

Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation.

BACKGROUND: In the Treatment with Ibutilide and Magnesium Evaluation (TIME) study, a retrospective multicentre cohort trial, prophylactic magnesium was found to improve the antiarrhythmic efficacy of ibutilide as demonstrated by an increase in the rate of successful chemical conversion and reduction in the need for direct current cardioversion (DCC). OBJECTIVE: The primary objective of this piggyback cost-effectiveness analysis of the TIME study was to compare the cost per successful conversion of atrial fibrillation (AF) for ibutilide in the presence and absence of magnesium prophylaxis. A secondary objective was to determine whether specific factors predict costs in the conversion of AF. METHOD: The study was conducted from the US hospital-payer perspective. Direct medical costs (USD, 2002 values) including drugs, intravenous admixture and administration, DCC, electrocardiographs and physicians' fees were obtained directly from the provider. Nonparametric bootstrapping was conducted to calculate confidence intervals for the incremental cost-effectiveness ratios. One-way sensitivity analysis was conducted varying efficacy, and drug, hospital and physician costs. Multivariate analysis was conducted to determine whether specific baseline factors were predictors of total cost. RESULTS: Total costs per patient were lower in the ibutilide plus magnesium group compared with ibutilide alone (USD1075 vs USD1201); however, the difference was not statistically significant (p = 0.116). Patients receiving ibutilide plus magnesium had lower DCC costs compared with those receiving ibutilide alone (USD261 vs USD399; p = 0.036), but higher magnesium-associated costs (USD0.50 vs USD0; p < 0.001). Bootstrapping revealed that the ibutilide plus magnesium strategy would result in lower costs and greater efficacy 93.4% of the time. These results remained robust to changes in both cost and efficacy. No baseline factors were found to be independent predictors of total costs. CONCLUSION: Our data suggest that adding prophylactic magnesium to ibutilide may be cost effective, from a US hospital-payer perspective, for the acute conversion of patients in AF or flutter compared with ibutilide alone.

Exploring the effects of ACE inhibitor tissue penetration on vascular inflammation following acute myocardial infarction.

BACKGROUND: Questions remain as to the existence of a class effect amongst angiotensin converting enzyme (ACE) inhibitors, and some literature suggests that pharmacological effects and outcomes may be determined by an ACE inhibitor's propensity to penetrate and inhibit the ACE enzyme at the vascular tissue level. Because vascular inflammation contributes to adverse outcomes following acute myocardial infarction (AMI), and angiotensin II influences inflammation at the vascular level, we hypothesized that high-tissue penetrating ACE inhibitors would provide more favorable effects on C-reactive protein (CRP) after AMI compared to low-tissue penetrating ACE inhibitors. METHODS AND RESULTS: In a randomized open-label trial, patients received the high-tissue penetrating quinapril (n = 15) or low-tissue penetrating enalapril (n = 15) following AMI. C-reactive protein was measured at baseline and periodically over 14 days following drug initiation. All baseline characteristics and blood pressure response to treatment between groups were equivalent. Prior to initiating study medication, CRP concentrations (mg/g) were similar between enalapril and quinapril (0.327 +/- 0.571 versus 0.273 +/- 0.380, respectively, p = 0.77). The percent magnitude of change in CRP concentrations favored quinapril at all time points, starting 12 h after treatment initiation. When characterizing CRP production during treatments, the time courses were significantly different and demonstrated lower CRP concentrations with quinapril (p = 0.0107). CONCLUSIONS: Overall, this investigation into the importance of ACE inhibitor tissue penetration on a common marker of vascular inflammation, suggests a potential vascular anti-inflammatory benefit with a more highly tissue penetrating ACE inhibitor following AMI. Further investigation into the true pharmacological similarities and differences amongst this class of drugs is warranted.

Questioning a class effect: does ACE inhibitor tissue penetration influence the degree of fibrinolytic balance alteration following an acute myocardial infarction?

There is a common belief in a class effect among angiotensin-converting enzyme (ACE) inhibitors. This is unsubstantiated for acute myocardial infarction (AMI). Because vascular tissue is a source of the endogenous fibrinolytic markers, and ACE inhibition in vascular tissue favorably influences the fibrinolytic system, the authors hypothesized that a high-tissue-penetrating ACE inhibitor would provide a more favorable reduction in plasminogen activator inhibitor-1 (PAI-1) and an increase in tissue plasminogen activator (t-PA) after AMI compared to a low-tissue-penetrating ACE inhibitor. In a randomized open-label trial, patients received the high-tissue-penetrating quinapril (n = 15) or low-tissue-penetrating enalapril (n = 15) immediately following an AMI. PAI-1 and t-PA antigen (ng/mL) were measured at baseline and through 14 days of treatment. There was no difference in baseline PAI-1 or t-PA antigen between treatments. PAI-1 antigen trended toward being lower with quinapril versus enalapril on day 1 (24.44 +/- 14.96 vs. 36.94 +/- 19.49, respectively, p = 0.059) and was significantly lower on day 3 (17.32 +/- 9.57 vs. 27.49 +/- 9.61, respectively, p = 0.009). Analysis of PAI-1 antigen over time by two-factor ANOVA with replication found significantly lower concentrations of PAI-1 antigen over the entire treatment period with quinapril versus enalapril (p < 0.003). This investigation of ACE inhibitor tissue-penetrating influence on markers of reinfarction risk suggests there may be a greater early reduction in PAI-1 with a more highly tissue-penetrating ACE inhibitor.

Impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion of atrial fibrillation or flutter.

The impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion of atrial fibrillation and flutter to normal sinus rhythm was studied. In this multicenter cohort study, all patients in three large, tertiary care centers who received ibutilide for acute chemical conversion of atrial fibrillation or flutter from August 1996 through December 2001 were identified through pharmacy or billing records. Patients who did not receive magnesium before or during ibutilide therapy served as the control group, while those who received magnesium less than two hours before or during ibutilide administration served as the study group. The rate of administration of direct-current cardioversion (DCC) and the occurrence of ventricular arrhythmia were compared between those who did and did not receive magnesium. The rates of successful cardioversion were also assessed. Categorical data were analyzed using chi-square analysis or Fisher's exact test. Demographic data were analyzed using Student's t test. The medical records of 321 patients were analyzed. Successful chemical cardioversion in the study group was approximately 19% higher than in those who did not receive magnesium (p = 0.040). The use of DCC in the group who received magnesium was reduced by approximately 34% (p = 0.045). The conversion rate of atrial fibrillation or flutter with ibutilide was enhanced by magnesium administration (p = 0.040), and the rate of administration of DCC was reduced (p = 0.045) in patients who received magnesium. There was a nonsignificant reduction in the occurrence of ventricular arrhythmias (p = 0.533). The efficacy of ibutilide was enhanced by concomitant administration with intravenous magnesium.