Low-molecular-weight heparins in coronary arterial thrombus disease: a review of the literature.

Popularity of low-molecular-weight heparins (LMWH) continues to grow. Clinical trials established their efficacy for various venous thromboembolic disease states. Their use in arterial disorders is also becoming widespread. Unfortunately, clinical trials in this population subgroup are either lacking or show little or no benefit of LMWH. Specifically, they appear to offer no benefit over antiplatelet agents, such as aspirin and ticlopidine, after percutaneous transluminal coronary angioplasty. Conversely, they may have a role in the management of unstable angina. At this time, however, their efficacy appears equivalent only to therapeutic dosages of unfractionated heparin.

Phenytoin malabsorption after jejunostomy tube delivery.

The literature supports interactions between phenytoin and both enteral feeding products and nasogastric feeding tubes; however, no published reports exist regarding the interaction of phenytoin with jejunostomy feedings. A 29-year-old woman with cerebral palsy, mental retardation, and a history of seizures was treated with intravenous phenytoin, which yielded detectable therapeutic serum concentrations. After switching to a comparable phenytoin suspension administered by jejunostomy tube, her serum phenytoin concentrations fell to below assay sensitivity concentrations. This drop, nearly 100%, was the greatest that we found reported in the literature. Distal placement of the jejunostomy tube within the small bowel may augment potential phenytoin-tube-enteral product interactions. In addition, the possible decrease in gastrointestinal transit time because of anatomic placement may not allow for adequate drug absorption. Decreased phenytoin bioavailability may become more common with increased use of supplemental feeding tubes.

The appropriateness of initial vancomycin dosing.

BACKGROUND: Vancomycin use has markedly increased over the past several years because of an increased incidence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus. Despite the availability of dosing nomograms and the use of peak and trough levels, vancomycin dosing has remained problematic. METHODS: All intravenous vancomycin orders over a 3-month period in a community and teaching hospital were screened for appropriateness of initial dosing based on available dosing nomograms. RESULTS: Of the 48 patients who received intravenous vancomycin, only 19 (39.6%) were given initial doses that achieved the desired serum concentration. There were no significant differences in the appropriateness of initial dosing between family medicine residents, attending physicians, and private staff physicians. Older patients in our study were at higher risk for overdosing, whereas younger patients were more likely to be underdosed. In this study, nomogram use could have yielded correct initial dosages in 40 of the 48 patients (83.3%). CONCLUSIONS: Our study indicates a high percentage of inappropriate initial vancomycin dosing in a community and teaching hospital. The investigators believe inappropriate initial vancomycin dosing is common and may result in unnecessary expense, increased risk of therapeutic failures, and greater potential for adverse drug reactions. Increased use of vancomycin dosing nomograms could improve the rate of correct initial dosages.

Ampicillin-specific rashes.

Ampicillin is one of the most common drugs to elicit a rash, with an overall incidence of 3% to 8%. "Ampicillin-specific" rashes are thought to be nonhypersensitivity reactions and cause maculopapular erythema with minimal irritation or pruritus. If the rash is indeed an ampicillin-specific one, then discontinuation of ampicillin is not mandatory, and subsequent use of ampicillin or other beta-lactam antibiotics is tolerated. On the other hand, true hypersensitivity reactions with urticarial and anaphylactic properties demand prompt discontinuation of the drug and warrant supportive care. Unfortunately, there is no immediate definitive scientific method to differentiate between the two.

Optimizing enteral nutrition.

Adequate nutritional support is an important aspect of the care of all patients. Enteral nutritional support accesses the gastrointestinal tract and includes both oral supplementation and tube-feeding techniques. Enteral nutritional support should be considered when a patient has functioning intestines but cannot or will not eat. Most patients require a caloric intake of 25 to 35 kcal per kg per day. The choice of route of administration for tube feedings should be based primarily on the anticipated length of therapy and patient comfort. Three schedules for the initiation and delivery of tube feedings are presented in this article. Both nasogastric and percutaneous endoscopic gastrostomy tubes are associated with potential complications, including aspiration and gastrointestinal intolerance. Important parameters include the patient's weight and volume status, and periodic laboratory determinations of the patient's serum electrolytes and protein status.

A critical review of the new oral cephalosporins. Considerations and place in therapy.

Oral cephalosporins are key antimicrobials in the family physician's therapeutic armamentarium. The list of available agents within this class has been recently expanded to include cefixime, cefprozil, cefpodoxime proxetil, and loracarbef. Each of these antibiotics has differing antimicrobial coverage patterns and approved therapeutic uses. Compared with older, more established antimicrobials such as penicillin, amoxicillin, cefaclor, a combination of amoxicillin and clavulanate potassium, and erythromycin, the newer cephalosporins offer little, if any, therapeutic advantage. Clinical efficacy has been shown to be equal in virtually all studies comparing the newer cephalosporins with traditional agents for various community-acquired infections. While the four newer agents may be given less often, they are relatively expensive. In light of the available clinical data, the newer oral cephalosporins should be reserved as second- or third-line choices.

Extended dosage intervals for aminoglycosides.

The rationale for and effectiveness of extended dosage intervals for aminoglycosides are discussed. Aminoglycosides can be given once daily despite an elimination half-life of two to three hours because of the postantibiotic effect (PAE) of these agents. Aminoglycosides have a prolonged PAE against a variety of common gram-negative and gram-positive organisms. Higher serum aminoglycoside concentrations are associated with longer PAEs and increased bactericidal activity. Once-daily administration may reduce the potential for adaptive postexposure resistance by allowing less contact time between organism and drug. A major concern with aminoglycosides is the risk of nephrotoxicity and ototoxicity. The uptake of specific aminoglycosides by renal cortical cells is saturable; a longer dosage interval may decrease the risk of nephrotoxicity because higher transient serum aminoglycoside levels appear to be less nephrotoxic than lower but more persistent serum concentrations. Once-daily administration may reduce the risk of ototoxicity through a similar mechanism. An increasing number of clinical trials suggest tht once-daily administration of aminoglycosides and regimens involving shorter dosage intervals are equally effective in patients with normal renal function and gram-negative infections and that once-daily administration may reduce the frequency of toxicity or delay it. Patients with renal dysfunction or neutropenia may also benefit from once-daily administration. Most trials have been small, and in some of them other antimicrobials were given concurrently. Although more study is needed, the evidence to date suggests that once-daily administration of aminoglycosides is as effective as traditional regimens entailing shorter dosage intervals and may reduce the potential for toxicity.

Evaluation of dosage-release formulations on inhibition of drug clearance: effect of sustained- and immediate-release verapamil on propranolol pharmacokinetic parameters.

Limited information exists regarding the influence of dosage-release formulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and sustained-release (SR) verapamil on the pharmacokinetic parameters of propranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Phase B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossover fashion. Of the 12 subjects enrolled, only seven were able to be analyzed secondary to assay interference. Oral clearances for L-propranolol for Phases A, B, and C were 198 +/- 70, 156 +/- 76, and 143 +/- 85 L/h, respectively. Oral clearances for D-propranolol for Phases A, B, and C were 203 +/- 96, 172 +/- 96, and 152 +/- 102 L/h, respectively. No significant differences were observed. However, when the verapamil groups (Phase B and C) were combined and compared to Phase A, a significant decrease in clearance for propranolol isomers was observed. In conclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the three treatment phases. However, there is a trend suggesting that SR verapamil had the greatest effect on propranolol clearance, which may warrant caution when changing from one formulation to another.