Clinical pharmacy最新文献

Findings on the efficacy of nutritional supplements used by athletes are reviewed. Many athletes have turned away from anabolic steroids and toward nutritional supplements in the hope of gaining a competitive edge without threatening their health. Athletes may require slightly more protein than sedentary people do to maintain positive nitrogen balance, but it is dubious whether extra dietary protein will help someone to achieve athletic goals. Purified amino acids have become a popular if expensive form of protein supplementation; there is no scientific evidence, however, to support their use. Excessive protein supplementation can lead to dehydration, gout, liver and kidney damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins and minerals in excess of recommended daily allowances appears to have no effect on muscle mass or athletic performance. Other substances touted as having ergogenic properties are carnitine, cobamamide, growth hormone releasers, octacosanol, and ginseng; again, there is no reliable scientific evidence to support claims that products containing these compounds have ergogenic potential, and heavy supplementation may lead to adverse effects. Nutritional supplements are promoted through unsubstantiated claims by magazine advertisements, health food stores, coaches, and other sources. The FDA considers nutritional supplements to be foodstuffs, not drugs, and therefore has not required that they be proved safe and effective. Dosage guidelines are inadequate, and quality control is poor. The FDA has begun to revise regulations governing labeling and health claims for these products. There is little if any evidence that nutritional supplements have ergogenic effects in athletes consuming a balanced diet, and some products have the potential for harm.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of sotalol hydrochloride are reviewed. The chemical name of sotalol hydrochloride is 4'-[1-hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide monohydrochloride. Sotalol is a class III antiarrhythmic that prolongs the action potential and refractoriness of cardiac tissue and has potent nonselective beta-blocking activity. Sotalol is well absorbed after oral administration. The pharmacokinetics of sotalol can be described by an open, linear, two-compartment model. The drug is eliminated primarily by the kidneys; mean elimination half-life is 12 hours. Sotalol has been found to be effective in controlling life-threatening ventricular arrhythmias, including sustained ventricular tachycardia, ventricular fibrillation, and premature ventricular complexes. Although sotalol has FDA-approved labeling for use in the treatment of ventricular arrhythmias only, it is also effective against a variety of supraventricular arrhythmias. Noncardiac adverse effects include fatigue, impotence, depression, headache, nausea, diarrhea, and increased triglyceride levels. Cardiovascular adverse effects include atrioventricular block, bradycardia, hypotension, exacerbation of heart failure, and polymorphic ventricular tachycardia. Overall, 11-21% of patients experience adverse effects; 6-18% of these patients have reactions serious enough to warrant the discontinuation of sotalol therapy. The initial dosage of oral sotalol hydrochloride in adults is 80 mg twice daily or 160 mg once daily; the dosage can be increased every three to four days in increments of 40-160 mg/day to a maximum of 480 mg/day. Sotalol is useful in the control of intractable, life-threatening ventricular arrhythmias, as well as a variety of supraventricular arrhythmias, in patients who do not respond to or are intolerant of more conventional antiarrhythmics.

The pharmacologic characteristics of low-molecular-weight (LMW) heparins and unfractionated heparin are reviewed, and clinical trials comparing LMW heparins with unfractionated heparin for the initial treatment of deep-vein thrombosis (DVT) are described. LMW heparins are derived from native heparin and range in mass from 3000 to 8000 daltons. All LMW heparins contain the antithrombin III-specific pentasaccharide unit found on unfractionated heparin. LMW heparins are stronger inhibitors of factor Xa than unfractionated heparin, but their mechanisms of action, like that of unfractionated heparin, is predominantly the inhibition of thrombin. The efficacy of LMW heparins in the prophylaxis of DVT is not correlated with activated partial thromboplastin time (APTT); monitoring of APTT or anti-factor Xa may not be necessary. Compared with unfractionated heparin, LMW heparins have a lower affinity for heparin cofactor II, platelet factor 4, von Willebrand factor, and vascular epithelium. Subcutaneously administered LMW heparins are more bioavailable than s.c. unfractionated heparin. In clinical trials in patients with DVT, LMW heparins (dalteparin, enoxaparin, nadroparin, and tinzaparin) have resulted in venography scores similar to those obtained with unfractionated heparin. Frequencies of recurrent thromboembolism and bleeding complications were also similar. Dalteparin and logiparin were effective when administered in single daily subcutaneous doses; this could lead to lower treatment costs. Additional studies are needed to compare LMW heparins and unfractionated heparin with respect to efficacy, bleeding complications, mortality, and cost. LMW heparins may be valuable alternatives to unfractionated heparin for the treatment of DVT.

The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenström's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is $3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL.

The pharmacology, pharmacokinetics, and clinical efficacy of zolpidem tartrate, a new hypnotic agent, are described. Zolpidem belongs to the imidazopyridine class. It exhibits high-affinity binding at a benzodiazepine-receptor subtype that is located in the cerebellum and cerebral cortex but not in the spinal cord or peripheral tissues. It decreases sleep latency and increases total sleep time and sleep efficiency without affecting sleep architecture. Zolpidem tartrate is absorbed rapidly. Bioavailability is 67% after oral doses of 5-20 mg. Pharmacokinetics show age-related and sex-related variations. The disposition of zolpidem is reduced in hepatically and renally impaired patients. Clinical studies have shown effectiveness of zolpidem in increasing sleep time and decreasing sleep latency. It has demonstrated efficacy equal to that of benzodiazepines without causing rebound insomnia or withdrawal effects. Comparative trials have found zolpidem as effective as flunitrazepam, flurazepam, and triazolam. The optimum dose of zolpidem tartrate is 10 mg at bedtime; 5 mg for elderly patients. Adverse reactions to zolpidem are dose-related and have primarily CNS and gastro-intestinal manifestations. Zolpidem exhibits similar efficacy to the benzodiazepines in the treatment of insomnia. Zolpidem's advantages over benzodiazepines are that it does not lead to tolerance, withdrawal phenomena, or REM rebound; however, for short-term, as-needed use, these advantages are not relevant.