Lisa A. Boothby

Vitamin C and Vitamin E for Alzheimer's Disease

OBJECTIVE To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimers disease (AD). DATA SOURCES Literature retrieval was accessed through MEDLINE (1966–March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimers disease, and dementia. International Pharmaceutical Abstracts (1970–March 2005), Current Contents (1996–March 2005), Cochrane Database of Systematic Reviews (1994–March 2005), and Ebscos Academic Search Elite (1975–March 2005) were searched with the same key words. STUDY SELECTION AND DATA EXTRACTION Articles related to the objective that were identified through PubMed were included. DATA SYNTHESIS Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E ≥400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses ≥400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted. CONCLUSIONS In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.

FDA Labeling System for Drugs in Pregnancy

OBJECTIVE: To review the current Food and Drug Administration (FDA) pregnancy labeling system, examine the new FDA-proposed pregnancy labeling system for form and content, and provide comments on its suitability for implementation. DATA SOURCES: Data were obtained from the FDAs Web site (www.fda.gov), PubMed, Federal Register, LexisNexis, Physicians Desk Reference (PDR), Drugdex, and Current Contents. STUDY SELECTION: Research and articles involving drugs and pregnancy, drugs and lactation, and the subcommittee meeting of the FDA were included. DATA EXTRACTION: Prospective, case-control studies from pregnancy registries. DATA SYNTHESIS: Currently, only 40% of drugs in the PDR have pregnancy categories listed. The medical profession has resorted to other means to assess pregnancy risk, such as retrospective chart review, case reports, and consultation with experts such as regional drug information centers. CONCLUSIONS: The proposed pregnancy labeling system strives for more clinical usefulness by reliance on human data derived from pregnancy registries. The clinical usefulness of the new labeling remains to be seen.

Treatment of Itching Associated with Intrahepatic Cholestasis of Pregnancy

OBJECTIVE: To review the drug therapy for the treatment of itching associated with intrahepatic cholestasis of pregnancy (ICP). DATA SOURCES: A comprehensive literature search was conducted in MEDLINE (1966–July 2002) using the following MeSH terms: pregnancy, itching, intrahepatic cholestasis, cholestyramine, ursodeoxycholic acid, and phenobarbital. Current Contents (1966–July 2002), International Pharmaceutical Abstracts (1970–June 2002), and Cochrane Database were also searched using those terms. Web of Science search was used to search references found in articles. DATA SYNTHESIS: Eight clinical trials and several observational studies were identified evaluating the safety and efficacy of ursodeoxycholic acid (UDCA) in the treatment of ICP. Although these studies were small and inconsistent, improvement in maternal and fetal morbidity was demonstrated. Observational studies suggest that cholestyramine may be associated with improved maternal morbidity without a documented improvement in fetal outcome. Two observational studies evaluated the efficacy of phenobarbital for ICP treatment. Phenobarbital use was not associated with improved maternal or fetal morbidity/mortality. CONCLUSIONS: Data from large, well-designed, randomized, controlled trials of treatment of ICP are lacking. Data that are available support the use of UDCA as a first-line agent and cholestyramine as a second-line agent for treatment of ICP. There is little evidence to recommend phenobarbital in the treatment of itching associated with that condition.

Bioidentical hormone therapy : a panacea that lacks supportive evidence

Purpose of review In the practice of ‘bioidentical hormone therapy’, it is our belief that pharmacists are compounding bioidentical hormone therapy with the best intentions. These pharmacists are, however, ill informed regarding the lack of scientific underpinning associated with the efficacy and safety of the practice of bioidentical hormone therapy. It is the purpose of this review to systematically examine the scientific rigor of the arguments posed by the proponents of bioidentical hormone therapy, and to differentiate the practice of bioidentical hormone therapy from the legitimate practice of pharmacy compounding. Recent findings Most medical organizations have in essence refuted the bioidentical hormone therapy claims as unsubstantiated. The profession of pharmacy needs to address this issue in an authoritarian, scientific way, outside of the compounding issue. Summary Bioidentical or natural hormones are expected to have similar efficacy and safety profiles as the commercially available hormonal therapies that have been studied in clinical trials, regardless of whether the active principle hormones are compounded by individual pharmacies or manufactured by large companies. Estriol is a weak estrogen that is not Food and Drug Administration approved for use as a prescription drug in the United States; thus, clinical trials are necessary to demonstrate the efficacy and safety profile for estriol. Further, supplementary clinical trials are necessary to determine whether there are efficacy or safety differences between natural progesterone and synthetic progestin, as studies to date are inconclusive.

Putting an Ecstasy Test Kit to the Test: Harm Reduction or Harm Induction?

Objective. To evaluate the DanceSafe Complete Adulterant Screening Kit for Ecstasy with regard to its accuracy in identifying 3,4‐methylenedioxymeth‐amphetamine (MDMA) and methylenedioxyamphetamine (MDA) derivatives and its ability to detect certain contaminants.

Carisoprodol: A marginally effective skeletal muscle relaxant with serious abuse potential

This review examines literature on the efficacy and abuse potential of carisoprodol, makes recommendations for use of this agent in the hospital setting, and outlines applicable federal and state regulations. A Medline search using key words and MeSH terms was conducted. In addition, International Pharmaceutical Abstracts (1970–2002), Current Contents (1996–2002), Cochrane Database of Systematic Reviews (1999–2002), and Psych Info (1872–2002) were searched for relevant literature. Articles cited in the bibliographies produced by these searches were included in the review. A Web of Science search was conducted for all citations found in all the searches. Pain is a common physical symptom in patients with musculoskeletal problems, and pharmacologic therapy is often combined with nonpharmacologic measures to treat the pain etiology and symptomatology. Skeletal muscle relaxants (SMRs) and nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most common drug therapy choices in patients with mild-to-moderate somatic pain. Carisoprodol (Soma) is an SMR that has a poorly defined mechanism of action and a high potential for abuse. This literature review produced little evidence to support the use of carisoprodol in pain control. The research also showed that patients with a history of previous substance abuse are more likely to abuse this drug; thus carisoprodol does not meet safety and efficacy standards and should be removed from the market. At the very least, states should reschedule carisoprodol as a schedule IV controlled substance to minimize chronic misuse and abuse. If carisprodol is listed in hospital formularies, it should be handled as a controlled substance regardless of its federal status. Alternative sedatives (eg, phenobarbital) should be used to manage patients experiencing carisoprodol withdrawal symptoms.

Development and Validation of an HPLC Method for Oxytocin in Ringer's Lactate and its Application in Stability Analysis

Abstract Oxytocin is an important therapeutic peptide; it is commonly used for the induction and augmentation of the first stage of labor. A simple, isocratic, reproducible, and selective HPLC method was developed and validated to study oxytocin stability in Ringers Lactate. A C8 column with mobile phase of acetonitrile and potassium dihydrogen orthophosphate buffer 0.05 M, pH‐7.0 (20:80, v/v) at a flow rate of 1.25 mL/min was used. The detection wavelength was 220 nm and 100 µL of sample was injected. Ethyl p‐aminobenzoate was used as the internal standard (I.S.). The retention time for oxytocin and I.S were 8.5 and 17 min, respectively, with a total run time of 20 min. Solid phase extraction was used and a lower limit of quantitation (LLOQ) of 0.0075 USP units/mL could be achieved. The method showed excellent linearity in the range 0.0075–0.9 USP units/mL. Oxytocin recovery ranged from 80–99%. Precision and accuracy were within the acceptable limits. The method was used to estimate oxytocin concentrations in Ringers Lactate over an extended period of time.

Academic detailing of meperidine at a teaching hospital

Meperidine (Demerol) is an opiate analgesic that is not considered first-line therapy for most pain management indications because of concerns about its safety and efficacy. Inpatient data from a 417-bed community teaching hospital revealed high use of meperidine in oral, IM, and IV forms. A multifaceted academic detailing approach was employed to change prescribing behavior and decrease meperidine use. This approach included conducting two concurrent Medication Use Evaluations; Grand Rounds presentations for pharmacy staff, nurses, and medical residents; solicitation of opinion leaders; pocket and table-top cards; newsletter articles; and provision of pharmaceutical care. Comparing the number of meperidine doses dispensed per adjusted patient day before and after the intervention, use was reduced by 0.0966 doses per patient (P < 0.05: 95% CI, 0.0955 to 0.0977). The number of patients receiving meperidine was reduced by 2.43% (P < 0.05: 95% CI, 1.97 to 2.88). This translates into a relative reduction of 29.5% in patients receiving meperidine and a relative reduction of 31% in meperidine doses dispensed per patient after academic detailing initiatives vs before. Eighty-five percent of standard orders were changed to improve therapy; these changes included converting meperidine to morphine or hydromorphone, decreasing cumulative acetaminophen daily dosages, using controlled-release and immediate-release opioids for pain management when oral therapy was tolerated, and combining modalities with different mechanisms of action for synergy and to decrease potential adverse effects from larger dosages of single entities. Academic detailing of meperidine resulted in short-term changes in prescribing patterns and decreased meperidine use at this institution. Long-term implications for pain management have not yet been assessed.