ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03545.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Temazepam is a 1,4‐benzodiazepine, newly marketed in the United States for the symptomatic treatment of the complaint of insomnia. The manufacturer recommends a dose of 30 mg before bedtime for most adults and 15 mg for geriatric or debilitated patients. A dose of 30 mg usually produces peak plasma concentrations within 3 hours after oral ingestion and has a mean half‐life of 10 to 15 hours. Thus, temazepam is absorbed more slowly and metabolized more quickly than flurazepam, the only other benzodiazepine marketed in the United States specifically for insomnia. Eight sleep laboratory and 21 clinical studies on temazepam indicate that temazepam reduces awakening during the night and increases sleep duration. However, there was no consistent evidence that temazepam reduces sleep latency — probably because temazepam, taken at bedtime, does not reach sufficiently high blood levels in time to affect sleep onset. One sleep laboratory study on 8 insomniac patients given 35 consecutive nightly doses of 30 mg found no evidence of tolerance or rebound insomnia. Studies on tolerance, metabolism and carry‐over effects have shown that temazepam has no long‐acting metabolites and does not affect waking function following use at bedtime. In patients for whom hypnotic medication is appropriate, temazepam should be an effective drug for reducing most symptoms of

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03546.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03547.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Trimethoprim has recently been marketed as a single‐entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram‐positive aerobic cocci and some gram‐negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition.Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused byE. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim‐sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging. (Pharmacotherapy 1981;

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03548.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03549.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Ibuprofen is a derivative of propionic acid that was originally marketed in the United States as an antirheumatic agent in 1974. In 1979, it was approved for use as an analgesic. Of the 18 published double‐blind clinical trials reviewed, only 6 were well designed. These six studies provide strong evidence that ibuprofen is effective for dental pain due to tooth extractions, dysmenorrhea and episiotomy pain. Thus, ibuprofen appears to be an effective drug for mild to moderate pain. It is as effective or more effective than aspirin, codeine or propoxyphene. Recommended initial dosage is 300 mg every six hours, increasing as needed to 400 mg every four hours. Adverse effects are relatively minor and infrequen

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03550.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Metronidazole is a 5‐nitroimidazole that has selective activity against anaerobic microorganisms, including bacteria and protozoa. Intravenous metronidazole has recently been approved by the U.S. Food and Drug Administration for the treatment of serious anaerobic bacterial infections. It is usually bactericidal at low concentrations, and its spectrum of activity encompasses almost all anaerobic bacteria and some capnophilic organisms. Anaerobic bacteria known to be resistant to metronidazole include occasional anaerobic cocci, some nonsporulating gram‐positive bacilli and propionibacterium. Metronidazole is the most active antimicrobial agent againstBacteroides fragilis, the most resistant of anaerobic bacteria. Kill‐curve studies demonstrate that there is a 2 to 5 log decrease in the number of colony forming units of S.fragilisandClostridium perfringenswithin one hour. The only well documented metronidazole‐resistant strain is aB. fragilisisolated from the normal flora of a patient on long‐term metronidazole therapy for Crohn's Disease. Metronidazole resistance inTrichomonas vaginalishas recently been described in a few strains that are able to survive at increased oxygen tensions. Metronidazole has been shown to be efficacious in certain protozoal infections including trichomonal vaginitis, extraintestinal amebiasis, and giardiasis. Clinical studies have shown metronidazole to be efficacious in the therapy of a variety of anaerobic infections, including non‐traumatic brain abscesses, intraabdominal sepsis, pelvic suppuration and necrotizing soft tissue infections. There have been disappointing results in the therapy of anaerobic pleuropulmonary infections with a number of superinfections caused by aerobic bacteria. Since metronidazole lacks any activity against aerobic bacteria, it must be combined with other agents, usually aminoglycosides, in the treatment of mixed infections involving anaerobic and aerob

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03551.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Myasthenia gravis is a neuromuscular disease that presents clinically as fluctuating weakness of one or more skeletal muscle groups. Weakness becomes more severe with exercise and improves with rest. The disease is caused by an autoimmune reaction at or near the post‐synaptic nicotinic acetylcholine receptor. The results of this immune reaction are the lytic destruction of the post‐synaptic membrane and a reduction in the number of acetylcholine receptors.Myasthenia gravis can be diagnosed by repetitive exercise of the involved muscles, administration of edrophonium (Tensilon), electrophysiologic testing, or demonstration of anti‐acetylcholine receptor antibodies.When the myasthenic weakness is mild or limited to the extraocular muscles, it may be treated with acetylcholinesterase inhibitors. When the weakness is more severe and/or more generalized, immunotherapy is most often indicated. Prednisone or prednisone plus thymectomy is the most frequently used form of immunotherapy. Azathioprine, 6‐mercaptopurine, plasmapheresis, or gamma globulin injections are other immunotherapeutic options that may be useful in selected patients.A large number of drugs may precipitate or exacerbate myasthenic w

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03552.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The rationale for pharmacokinetic monitoring of aminoglycosides is critically reviewed. Retrospective studies suggest that for optimal antibacterial effect, peak serum gentamicin concentrations should exceed 5 μg/ml, despite the fact that these concentrations are indirect measures of the concentration of drug at the site of infection. When quantitative results of antimicrobial susceptibility are known (e.g. MIC or MBC), limited data suggest that for most infections, the peak serum aminoglycoside concentration should exceed the minimum inhibitory concentration by four‐fold. However, the optimal duration for which the serum concentration should exceed the MIC or MBC during each dosing interval and the detrimental effect of prolonged subinhibitory drug concentrations have not been evaluated. Furthermore, the immunological competence of the host and the pathogenicity of the infecting organism are important factors in achieving antibacterial response.Using serum creatinine as an indirect and relatively late indicator of nephrotoxicity, nadir gentamicin concentrations greater than 2 μg/ml may predispose patients to develop nephrotoxicity. In addition, recent information indicates that patients who accumulate excessive amounts of aminoglycosides In their tissues may be at higher risk for developing nephrotoxicity; these patients may be identified based on the extent of accumulation in their nadir concentrations with continuous dosing. The aminoglycosides diffuse into the inner ear fluids slowly and diffuse out with a half‐life of decline in inner ear fluid concentrations slower than that in serum. High transient peak serum concentrations probably do not contribute significantly to the risk of ototoxicity. However, there is evidence from early clinical trials, studies using continuous infusions of aminoglycosides, and animal studies indicating that elevated nadir serum concentrations relate to the development of ototoxicity.There is considerable interpatient variability in the peak serum concentration, even when identical dosages based on body weight or surface area are administered. Similarly, the half‐life for decline In serum concentrations is highly variable from patient to patient, even in patients with stable normal renal function. Absorption after intramuscular administration is reliable in most patients, although critically ill patients may experience erratic absorption. The distribution of aminoglycosides is altered in obese patients because of differences in extracellular fluid content between fat and other tissues. Maintaining serum aminoglycoside concentrations in the desired therapeutic range is difficult in patients with impaired renal function, and frequent monitoring of serum concentrations is essential in these patients. Neonates, infants and children differ from adults in their ability to eliminate aminoglycosides and in their central volume of distribution. Fever, state of hydration, “third‐spaces”, and concurrent penicillin therapy may also affect the pharmacokinetics of the aminoglycosides. Diseases which affect some of the factors mentioned above (e.g. burns) may cause unpredictable changes in pharmacokinetic behavior.The approach at St. Jude Children's Research Hospital to pharmacokinetic monitoring of aminoglycoside therapy in children with cancer is presented. This method accounts for tissue accumulation, and allows for dosage adjustments using individualized pharmacok

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1981.tb03553.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY