Melody Ryan

Factors Leading Patients to Discontinue Multiple Sclerosis Therapies

OBJECTIVES To determine the percentages of patients who discontinued treatment with the multiple sclerosis medications intramuscular interferon beta-1a (IFN-beta-1a; Avonex-Biogen), interferon beta-1b (IFN-beta-1b; Betaseron-Berlex), and glatiramer acetate (Copaxone-Teva) and to determine the factors that led to discontinuation of the medications. DESIGN Cross-sectional study. SETTING University-based neurology clinic. PATIENTS 108 patients with multiple sclerosis who were prescribed intramuscular interferon beta-1a, subcutaneous interferon beta-1b, or subcutaneous glatiramer acetate. INTERVENTION Telephone survey. MAIN OUTCOME MEASURES Discontinuation percentages and the factors that contributed to discontinuation. RESULTS There was no significant difference between the percentages of patients who discontinued and did not restart treatment with the products (interferon beta-1b, 41%; intramuscular interferon beta-1a, 34%; and glatiramer acetate, 28%). Four main reasons for medication discontinuation emerged: adverse effects (52%), physician-documented disease progression (40%), patient perception of drug ineffectiveness (20%), and cost (4%). No statistical differences were identified among the three agents for any of the reasons for discontinuation. CONCLUSION Patient education on adverse effects and realistic patient expectations may be potential areas of study to improve discontinuation percentages with these agents.

Use and monitoring of bromides in epilepsy treatment

Bromides are no longer a mainstay of epilepsy therapy because of the significant toxicity associated with their use and the availability of safer agents. However, bromides occasionally find a niche in the treatment of patients with refractory seizures, particularly in pediatrics. When the decision to utilize this therapy is made, the clinician may be frustrated by the lack of concise, current information regarding bromides. This review provides an update on the mechanism of action, efficacy, pharmacokinetics, dose, and adverse effects of bromides.

Topiramate concentration in saliva: an alternative to serum monitoring.

This study examines the relationship between serum and saliva topiramate concentrations, and attempts to determine if saliva may be a useful alternative to serum for therapeutic monitoring. Saliva and blood specimens were collected from 31 epilepsy patients (mean age 10.5 +/- 6.0 years; range 2.5 years to 24.8 years), and topiramate concentrations were determined by fluorescence polarization immunoassay. One patients results were omitted because the saliva concentration was below the limit of quantitation of the assay. A strong correlation exists between serum and saliva topiramate concentrations (adjusted r(2) = 0.97, n = 30, P < 0.0001). The mean fraction of saliva to serum concentration is 89.8% +/- 12.1% (range 62.9% to 112.7%). The results of this study support the use of saliva as a viable alternative to serum for monitoring topiramate therapy. Topiramate concentration in saliva: an alternative to serum monitoring.

Seizures in HIV-seropositive individuals: epidemiology and treatment.

Seizures are a relatively common occurrence in patients with HIV infection. They may be a result of HIV infection of the CNS or a manifestation of an opportunistic infection. Because seizures are likely to recur in patients infected with HIV and because they are a poor prognostic indicator, it is generally recommended that all HIV-seropositive patients experiencing a first seizure without a recognisable and reversible cause be treated. Clinicians faced with treating seizures in HIV-seropositive patients often encounter a therapeutic dilemma since few data exist in this area. In selecting appropriate anticonvulsant therapy, clinicians must consider both therapy-compromising drug-drug and drug-disease interactions. Ideal anticonvulsants for this setting are those that do not effect viral replication, have limited protein binding and have no effects on the cytochrome P450 system, such as gabapentin, topiramate and tiagabine. Unless the benefits outweigh the risks, valproic acid (sodium valproate) should be avoided as it has been shown to stimulate HIV replication. Since few data exist, controlled trials examining pharmacokinetic and pharmacodynamic interactions between anticonvulsants and antiretrovirals are needed. Until such time, clinicians caring for these patients should examine existing data carefully and employ vigilant monitoring.Seizures are a relatively common occurrence in patients with HIV infection. They may be a result of HIV infection of the CNS or a manifestation of an opportunistic infection. Because seizures are likely to recur in patients infected with HIV and because they are a poor prognostic indicator, it is generally recommended that all HIV-seropositive patients experiencing a first seizure without a recognisable and reversible cause be treated. Clinicians faced with treating seizures in HIV-seropositive patients often encounter a therapeutic dilemma since few data exist in this area. In selecting appropriate anticonvulsant therapy, clinicians must consider both therapy-compromising drug-drug and drug-disease interactions. Ideal anticonvulsants for this setting are those that do not effect viral replication, have limited protein binding and have no effects on the cytochrome P450 system, such as gabapentin, topiramate and tiagabine. Unless the benefits outweigh the risks, valproic acid (sodium valproate) should be avoided as it has been shown to stimulate HIV replication. Since few data exist, controlled trials examining pharmacokinetic and pharmacodynamic interactions between anticonvulsants and antiretrovirals are needed. Until such time, clinicians caring for these patients should examine existing data carefully and employ vigilant monitoring.

A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer’s disease

The past decade has seen an increase in therapeutic options for Alzheimer’s disease (AD) that target neurotransmitters, such as acetylcholine, and research continues to target abnormal proteins in the AD brain. Recently, glutamate excitotoxicity has also become a target for AD treatment with the advent of memantine. Clinical trial data reviewed for memantine show good tolerability, low side-effect profiles and a positive therapeutic impact in moderate-to-severe AD, both as monotherapy and in conjunction with donepezil. However, additional data suggest variable benefits in the mild stages of AD. Furthermore, published reports support reduced dosing in patients with significant renal disease. However, the opportunity to target a second mechanism in the treatment of AD, thereby providing added symptomatic benefit, appears to be a useful consideration for clinicians who treat this devastating neurodegenerative disorder.

Stability of salivary concentrations of the newer antiepileptic drugs in the postal system.

Saliva antiepileptic drug (AED) concentrations strongly correlate with serum concentrations. Saliva collection is painless and noninvasive, and untrained personnel can easily be taught the collection process. Remote patients could mail saliva samples to a laboratory for monitoring, and samples could be obtained in the immediate postictal state to provide a “real-time” concentration. The objectives of this study were to assess the stability of saliva lamotrigine (LMT), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), and zonsiamide (ZNS) concentrations sent through the United States Postal Service (USPS) and to quantify the amount of time needed for patients and the USPS to return samples to clinic. Saliva samples were obtained from patients currently taking 1 of the targeted AEDs. Samples were split into 2 storage vials. One sample was sealed in an addressed envelope, which the patient mailed from home, whereas the other sample was frozen immediately. Postmark date and day returned were collected for mailed samples. Saliva concentrations were determined using HPLC. Wilcoxon rank sum tests were used to compare the immediately-frozen and mailed sample means. Correlations were determined by the Spearman test. Thirty-seven patients were enrolled in the study. The median time between collection and postmark was 1 day (range 0-6 days); and between collection and receipt was 4 days (range 1-160 days). The mean concentrations for mailed and immediately frozen samples were similar for each AED (P > 0.15). Spearman rank order correlations between mailed and immediately frozen aliquots were strong (LMT rs = 1, LEV rs = 1, OXC rs = 0.964, TPM rs = 0.90, and ZNS rs = 1). Saliva samples mailed by patients maintain stability and can be returned in a reasonable length of time. Further studies are needed to assess patient/caretaker capability of obtaining an adequate sample.

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD).

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Childrens Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 ± 10.0 μg/mL, and the mean saliva concentration was 23.1 ± 10.1 μg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 ± 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.

Correlation of Lamotrigine Concentrations between Serum and Saliva

Study Objective. To compare the relationship between serum and salivary concentrations of lamotrigine in pediatric and adult epilepsy populations.

Factors Associated With Pharmacy Student Interest in International Study

Objectives. To examine the interest of pharmacy students in international study, the demographic factors and involvement characteristics associated with that interest, and the perceived advantages and barriers of engaging in international opportunities during pharmacy school. Methods. A self-administered electronic survey instrument was distributed to first-, second-, and third-year pharmacy students at the University of Kentucky College of Pharmacy. Results. There were 192 total respondents, for a response rate of 50.9%. Seventy-two percent reported interest in international study. Previous international study experience (p=0.001), previous international travel experience (p=0.002), year in pharmacy school (p=0.03), level of academic involvement (p<0.001), and level of diversity involvement (p<0.001) were associated with international study interest. Positive influences to international study included desire to travel and availability of scholarships. Perceived barriers included an inability to pay expenses and lack of foreign language knowledge. Conclusions. The needs and interests of pharmacy students should be considered in the development and expansion of internationalization programs in order to effectively optimize global partnerships and available international experiences. Colleges and schools of pharmacy should engage students early in the curriculum when interest in study-abroad opportunities is highest and seek to alleviate concerns about expenses as a primary influence on study-abroad decisions through provision of financial assistance.

Association of antiepileptic drugs, vitamin D, and calcium supplementation with bone fracture occurrence in epilepsy patients.

The aim of this study is to determine whether calcium and vitamin D supplementation reduces the risk of bone fractures in adult epilepsy patients. Records were obtained on 7716 patients with epilepsy prescribed antiepileptic drugs (AED) from the Veteran Affairs Hospital in Lexington, Kentucky. We performed a single center, retrospective cohort study to examine the proportion of fractures in 3303 patients on AED who took supplements compared to patients on AED not taking supplements. Patients prescribed long-term AEDs taking calcium and vitamin D were as likely to have fractures as those who did not take these supplements (11.7% vs. 9.9%, χ(2)=0.59, p=0.44). Phenytoin use was associated with a statistically significant increased risk of fractures OR=1.55 (1.10-2.24). Thus, in this group of patients with epilepsy on AED, bone fractures were not prevented in individuals taking calcium and vitamin D supplementation.