Use of antioxidant supplements and its association with cognitive function in a rural elderly cohort: the MoVIES Project. Monongahela Valley Independent Elders Survey.

There has been much interest recently in the therapeutic benefits of antioxidants, including a possible protective role in preventing or delaying cognitive decline. This study describes the use of antioxidant supplements among 1,059 rural, noninstitutionalized elderly residents of southwestern Pennsylvania who are participants in the Monongahela Valley Independent Elders Survey. The data were collected during the survey's second wave of follow-up (1989-1991). The mean age of participants was 74.5 years (standard deviation 5.5), and 57.3% were women. Current use of nutritional supplements containing vitamin A, C, or E, beta-carotene, zinc, or selenium was measured through self-report. Subjects were administered a battery of 15 neuropsychological tests measuring performance in several cognitive domains. Of the 1,059 persons, 342 (32.3%) were taking antioxidant supplements. Women and persons with higher levels of education were more often antioxidant users. Antioxidant use did not vary significantly by age, race, or income. In univariate analyses, antioxidant use was significantly and positively associated with performance on several cognitive tests. However, after adjustment for age, education, and sex, there were no significant differences in cognitive test performance between antioxidant users and nonusers. This study is one of only a few that have analyzed the relation between antioxidants and cognition in a community-based sample. After potentially confounding factors are accounted for, the results do not support the hypothesis that antioxidant supplement use is associated with cognitive function.

Over-the-counter medication use in an older rural community: the MoVIES Project.

OBJECTIVE: To examine the self-reported use of over-the-counter (OTC) medications and the factors associated with OTC use in a rural older population. DESIGN: A cross-sectional study of an age-stratified random community sample. SETTING: The mid-Monongahela Valley, a rural area of Southwestern Pennsylvania. PARTICIPANTS: A total of 1059 older individuals with a mean age of 74.5 (+/- 5.5) years, 96.9% of whom were white and 57.3% of whom were women. MEASUREMENTS: Self-reported over-the-counter drug use and demographic information, and information about prescription drug use and recent use of health services. RESULTS: The majority (87.0%) of the sample were taking at least one OTC medication; 5.7% reported taking five or more OTCs. Women took significantly more OTCs than did men (P < .001). Individuals with more education took significantly more OTCs than those who had less (P = .018). The OTC category used most commonly was analgesics (66.3% overall), followed by vitamin and mineral supplements (38.1%), antacids (27.9%), and laxatives (9.7%). The use of analgesics decreased significantly (P = .018) with increasing age, whereas the use of laxatives increased significantly (P < .001). Women were more likely than men to be using each of these four major OTC groups. Unlike the associations with prescription drug use we reported previously in the same population, there were no significant associations for overall OTC use with age or with the use of health services. However, although vitamin use (as an example of an OTC drug taken for "preventive" purposes) was not associated with health services use, the use of laxatives (as an example of a "curative" OTC) was significantly associated (P < or = .002) with a greater number of physician visits, emergency room visits, hospitalizations during the past 6 months, home health care service utilization, and number of prescription medications. CONCLUSIONS: A substantial proportion of our older sample reported using a variety of over-the-counter drugs. Analgesics and vitamin/mineral supplements were the most frequently used categories. Women and those with more education were taking more OTC drugs. OTC use was not related to age, but the use of analgesics decreased with age while laxative use increased with age. Unlike prescription drug use, overall OTC drug use was not associated with health services utilization.

Use of prescription medications in an elderly rural population: the MoVIES Project.

OBJECTIVE: To determine the pharmacoepidemiology of prescription drug use in a rural elderly community sample, specifically the numbers and categories of medications taken and the factors associated with them. DESIGN: Cross-sectional community survey. SETTING: The mid-Monongahela Valley of southwestern Pennsylvania. PARTICIPANTS: An age-stratified random sample of 1360 community-dwelling individuals, aged 65 years and older. MEASURES: Self-reported use of prescription drugs demographic characteristics, and use of health services. RESULTS: Nine hundred sixty-seven participants (71%) reported regularly taking at least one prescription medication and 157 (10%) reported taking five or more medications (median 2.0, range 0-13). Women took significantly more medications than men (median 2.0, range 0-13 and median 1.0, range 0-9, respectively; p = 0.01). The use of a greater number of medications was independently and statistically significantly associated with older age, hospitalization within the previous 6 months, home health care in previous year, visit to a physician within the previous year, and insurance coverage for prescription medication. Individuals older than 85 years were significantly more likely to be taking cardiovascular agents, anticoagulants, vasodilating agents, diuretics, and potassium supplements. Significantly more women than men were taking nonsteroidal antiinflammatory drugs, antidepressants, potassium supplements, and thyroid replacement medications. CONCLUSIONS: Both the number and the types of prescription medications vary with age and gender. The demographic and health service use variables associated with greater medication use in the community may help define high-risk groups for polypharmacy and adverse drug reactions. Longitudinal studies are needed.

Empiric antibiotic selection by physicians: evaluation of reasoning strategies.

The objectives of the study were to evaluate the appropriateness of empiric antibiotic selection by housestaff treating medical patients with bacteremia. The design was a prospective, observational study at a university-affiliated hospital. Seventy-eight patients with bacteremia were evaluated. A clinical grade of acceptable or not acceptable was assigned to each antibiotic prescription by a consensus panel. The consensus panel found that 34.6% of antibiotic prescriptions were unacceptable (clinical grade). At least one flaw in the chain of reasoning was found in 56.4% of the 78 cases evaluated. Assessment of the clinical setting was correct in 94.9% of the cases; the portal of entry was identified in 91%; adequate knowledge of the bacterial flora at the suspected site of infection was found in 69%; the diagnostic workup was appropriate in 81%, and the correct antibiotic susceptibility patterns were given in 72%. A correct chain of reasoning was more likely to result in an acceptable clinical grade than flawed reasoning (p less than 0.005). However, an appropriate antibiotic selection was made by some physicians despite flawed reasoning, and inappropriate antibiotic selection occurred in a few cases despite fautless reasoning. In 3.8% of cases, unexpected organisms appeared in blood culture. Prescription of broad spectrum antibiotics may then be learned response. If so, educational efforts that emphasize narrow, rather than broad spectrum prescribing may be inadequate to change physician prescribing habits.

Clindamycin pharmacokinetics and tissue penetration after head and neck surgery.

Penetration of clindamycin into surgical wounds was studied in 10 patients undergoing radical head and neck surgery. Patients received one preoperative and three postoperative intravenous doses of clindamycin 600 mg. During surgery, samples of plasma and sternocleidomastoid muscle were obtained. Additional plasma samples were collected just before the fourth dose of clindamycin, just after that dose was infused, and 1, 2, 4, 6, 8, and 12 hours after dosing. Samples of wound exudate were collected at 2, 4, 6, 8, and 12 hours after the fourth dose. The muscle, plasma, and wound exudate samples were assayed for clindamycin base by a gas-liquid chromatographic method. Plasma and wound exudate samples obtained during surgery and one and eight hours after the fourth dose were assayed by a radial immunodiffusion technique for content of alpha 1-acid glycoprotein (AAG), the major binding protein for clindamycin. Pharmacokinetic values for plasma and wound drainage were calculated and compared. Concentrations of clindamycin in muscle (three to six hours after the first dose) ranged from 0.6 to 5.1 micrograms/g; the ratio of tissue to plasma concentrations ranged from 0.24 to 0.82. The highest mean clindamycin concentration in wound drainage was 4.9 micrograms/mL after the fourth dose, approximately 90% of simultaneous plasma concentrations. Concentrations in wound exudate exceeded those measured in plasma four hours after the dose, and elimination from the wound was slower than from plasma. AAG concentrations in plasma increased from a mean of 89 mg/dL intraoperatively to 134 mg/dL postoperatively. AAG was present in wound exudate in concentrations that were approximately 53% of those observed in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of methods for determining unbound theophylline concentrations.

In order to determine the suitability of using tears and saliva to estimate theophylline concentrations, simultaneous plasma, tear, and saliva samples were obtained in 22 adult male patients taking theophylline. Unbound theophylline concentrations were determined by equilibrium dialysis for nine of the subjects and compared with the concentrations determined in saliva and tears. The mean tear/unbound and saliva/unbound ratios were 0.94 +/- 0.12, r = 0.88, and 1.25 +/- 0.14, r = 0.91, respectively. Tear/plasma ratios ranged from 0.36 to 0.76 (mean 0.58 +/- 0.11), and tear concentrations correlated well with plasma concentrations (r = 0.94). Saliva/plasma ratios ranged from 0.52 to 1.16 (mean 0.79 +/- 0.19), and there was a positive correlation between plasma and saliva concentrations (r = 0.84). The mean tear/unbound and saliva/unbound ratio predicted the unbound concentration within 1 microgram/ml in 50 and 78% of the cases, respectively. Saliva and tears have limited clinical value in estimating the unbound concentration of theophylline.

Pharmacodynamic evaluation of the benzodiazepine-oral contraceptive interaction.

The sedative, psychomotor, and memory effects of single oral doses of alprazolam (ALP), lorazepam (LOR), temazepam (TMP), and triazolam (TRZ) were evaluated in women taking oral contraceptives (OCs) and a comparable group of control women. Nine women taking OCs and 11 control women took doses of 1 mg ALP and 2 mg LOR and 10 OC users and 10 control women took 30 mg TMP and 0.5 mg TRZ on two occasions separated by 28 days. Minimal psychomotor impairment was noted after TMP. ALP, LOR, and TRZ produced greater performance impairment in the OC users. Correcting the maximum observed performance decrement for plasma concentration did not account for the differences between OC users and controls. After TMP, there was less sedation during the first 2 hours in OC users, who also had higher plasma TMP clearance. There were no differences in sedation between OC users and controls after ALP, LOR, and TRZ; however, there was less than 50% power to detect a 30% difference. Amnestic effects in OC users and controls did not differ after any of the four drugs. The observed patterns of anterograde amnesia were different, with the earliest and most pronounced recognition failure after TRZ (50% at 1.5 hours), while the LOR effect increased to a maximum (30%) 4 hours after dosing. Our data suggest that differences in benzodiazepine pharmacokinetics between OC users and control women do not account for observed differences in psychomotor impairment. Women taking OCs are more sensitive to the psychomotor effects of single oral doses of benzodiazepines.(ABSTRACT TRUNCATED AT 250 WORDS)

The excretion of rosaramicin in breast milk.

The excretion of rosaramicin, a macrolide antibiotic, was studied in the breast milk of ten lactating women. Breast milk and serum samples were collected for 48 hours after a single 250-mg oral dose of rosaramicin. Mean serum half-life, apparent volume of distribution, and oral clearance were 4.4 hours, 3.41 L/kg, and 6.34 mL/min/kg, respectively. Mean milk/serum ratio was 0.12 and the total amount of drug recovered over the first ten hours was 6.25 micrograms, approximately 0.0025% of the dose. A positive correlation between breast milk volume and breast milk clearance was found, suggesting that the amount of drug received by a nursing infant will depend on the volume of milk produced by the mother. Drug-induced toxicity from the parent drug is unlikely to occur in nursing infants since the amount of rosaramicin that a nursing infant could ingest is small.

Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics.

The effects of low-dose estrogen oral contraceptives (OC) on the elimination of the oxidized benzodiazepines triazolam (TRZ) and alprazolam (ALP) and the conjugated benzodiazepines temazepam (TMZ) and lorazepam (LOR) were studied in two parallel crossover studies of 20 women each. Women taking OC steroids containing low doses of estrogen and women matched for age, weight, and cigarette smoking received single oral doses of TRZ (0.5 mg) and TMZ (30 mg) or ALP (1 mg) and LOR (2 mg). Kinetics were determined as plasma concentrations during 48 hr after dosing. OCs inhibited the metabolism of ALP: The AUC increased and the elimination rate constant was greater in users of OCs. For TRZ, which has an intermediate extraction ratio, the AUC was increased by OCs but not significantly so. In contrast, OCs decreased the AUC for TMZ and the elimination rate constants for LOR and TMZ. The AUC of LOR was not affected by OCs. Low-dose estrogen OCs may therefore inhibit the metabolism of some oxidized benzodiazepines and accelerate the metabolism of some conjugated benzodiazepines.

PIP: Because benzodiazepines and oral contraceptives (OCs) are among the most widely prescribed drugs and have a potential for interaction, 2 parallel crossover studies were conducted to determine the effects of OCs on the elimination of the oxidized benzodiazepines triazolam (TRZ) and alprozolam (ALP) and the conjugated benzodiazepines temazepam (TMZ) and lorazepam (LOR). 20 healthy women taking OCs containing does of under 35 mcg of ethinyl estradiol for 3 months or more and 20 women matched for age, weight, and cigarette smoking received single oral doses of TRZ (.5 mg) and TMZ (30 mg) or ALP (1 mg) and LOR (2 mg). Treatments were seperated by 28 days to control for effects of menstural cycle on drug metabolism. Kinetics were determined as plasma concentrations during 48 hours after dosing. The data indicated that OCs differentially affect the elimination of the benzodiazepines studied. OCs inhibited the metabolism of ALP: the area under the curve (AUC) increased and the elimination rate constant was greater in users of OCs. For TRZ, which has an intermediate extraction ratio, the AUC was increased by OCs but not significantly so. OCs decreased the AUC for TMZ and the elimination rate constants for LOR and TMZ. The AUC of LOR was not affected by OCs. It was concluded that low-dose estrogen OCs may inhibit the metabolism of some conjugated benzodiazepines and accelerate the metabolism of some conjugated benzodiazepines, but the clinical implications are unclear. The relationship between plasma concentration and effect has not been determined for most benzodiazepines, but the results suggest that the time required to achieve steady-state concentrations would be longer and that there would be higher steady state concentrations of ALP in OC users. Because both TMZ and LOR are eliminated more rapidly by OC users, women taking OCs should achieve steady-state concentrations more rapidly than nonusers. Because TMZ clearance is increased by OCs, mean plasma concentration may be decreased. The usual 30 mg dose of TMZ may therefore be less effective as a hypnotic in OC users.

Managing drug interactions with oral contraceptives.

An increasing concern to nurses is the possibility of drug interactions involving oral contraceptives. Information regarding the mechanisms, significance, and management of drug interactions with oral contraceptives is provided. Approaches to counseling patients also are discussed.

PIP: Drus interactions involving oral contraceptives (OCs) are of increasing concern. Antitubercular drugs, anticonvulsants, and antibiotics are among the drugs believed to alter the efficacy of OCs. Rifampin, for example, appears to induce an increase in the rate of metabolism of OCs, resulting in unacceptable rates of breakthrough bleeding and pregnancy. Phenobarbital stimulates the liver's drug metabolizing enzymes and may alter the disposition of some progestogens by increasing their binding affinity to plasma proteins. In addition, OCs may affect the activity of certain drugs and vitamins, including anticoagulants, vitamin B6, and folic acid. Conscientious family planning nurse practitioners can play an important role in the management of these drug interactions. OC users who require antibiotic therapy should be monitored for signs of diminished estrogen effect. Women receiving anticoagulants should be monitored when OCs are either begun or discontinued, and weekly or twice weekly determinations of prothrombin time may be required. Significant drug interactions may indicate the need for another means of contraception. Effective contraceptive counseling in such cases requires a sympathetic approach and a review of alternate contraceptive methods. Techniques of insertion, known side effects, and noncontraceptive benefits should be discussed. Patients who are switched to another OC preparation should be instructed to report breakthrough bleeding. Family planning nurse practitioners, especially those working with very young or low income women, should stress the need for adequate nutrition. In some cases, nutritional supplements may be indicated. In addition, patients should be instructed to question other health care providers about possible interactions with OCs whenever drug therapy is prescribed.