Conflicting data in the literature: a true dilemma.
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Drug Therapy↗
Biomedical subjects
C S Conner
Publications and source records attributed to C S Conner.
beta-Lactamase inhibitors.
Numerous beta-lactamase inhibitors have been developed to overcome the problems of bacterial resistance to beta-lactam antibiotics. One such agent, clavulanic acid, has been combined with amoxicillin, and the combination is effective against many amoxicillin-resistant organisms. Clinical studies have demonstrated the efficacy of amoxicillin/clavulanate in a variety of infections, however, comparative studies are few and have not demonstrated sufficiently the superiority of the combination over conventional antibiotic therapy. In addition, side effects appear to be more frequent than with amoxicillin alone. The place in therapy of amoxicillin/clavulanate is discussed.
Amoxicillin↗
Therapy with monoclonal antibodies.
Monoclonal antibodies (MABs) are an exciting development in the field of clinical immunology. Secreted in large amounts from hybrid myeloma (hybridoma) cell lines, MABs are directed at a specific antigen, such as tumor cell antigens, providing a major advantage over conventional, heterogeneous antisera. MABs have shown promise in the treatment of cancer, producing remission in some patients with leukemia and lymphoma. The future uses of MABs are enormous, including passive immunization against infections and allergies, treatment of autoimmune disease, and specific antibody treatment of drug intoxications. The impact of MAB technology on clinical medicine will be felt in the years to come.
Antibodies, Monoclonal↗
Ribavirin.
Despite the plethora of antibiotics available for the treatment of bacterial infections, very few agents have been developed to treat viral diseases. Ribavirin (Virazole) is a triazole nucleoside antiviral agent that produces selective antiviral effects against a broad spectrum of RNA and DNA viruses. The drug has been effective in the treatment of naturally occurring influenza A and B infections when administered by aerosol; oral administration has been ineffective. Ribavirin aerosol therapy also has proven effective to reduce symptoms of respiratory syncytial virus infections in young adults and hospitalized neonates. Ribavirin aerosol may be the first antiviral agent to treat these common diseases.
Adult↗
Marijuana and alcohol use in pregnancy.
The literature is sparse on the adverse effects of moderate alcohol consumption and marijuana use during pregnancy. Recent studies have evaluated the association of these drugs of abuse with pregnancy outcome, each using interview and medical record data of over 12 000 women. Children of marijuana users were more likely to have one or more major malformations, lower birthweight, and shorter gestation than children of nonusers. However, when logistic regression was used to control for other variables, these relationships were not statistically significant. The odds ratio for major malformations does, however, remain suggestive for marijuana. The use of similar logistic regression techniques revealed that the only statistical association between alcohol intake of 14 or more drinks per week was placenta abruptio. With the exception of placenta abruptio, alcohol intake of fewer than 14 drinks weekly was not associated with an increased risk of any adverse outcome. There was no association between alcohol use at any level and the rate of congenital malformations. Recommendations based on these data are presented.
Abnormalities, Drug-Induced↗
Isotretinoin: a reappraisal.
Isotretinoin is remarkably effective in the treatment of severe cystic acne, however, many complications have been observed during treatment and new toxic effects have been reported. Hypertriglyceridemia associated with decreases in high density lipoprotein (HDL) cholesterol has occurred in 25 percent of patients and requires monitoring during treatment. Painful erosions with granulation tissue recently have been reported in patients with severe acne. Other complications have included corneal opacities, pseudotumor cerebri, hypercalcemia, photosensitivity reactions, abnormal liver function tests, and skeletal hyperostosis. Isotretinoin is teratogenic and should be avoided during pregnancy. With the increasing acceptance and use of isotretinoin for cystic acne, as well as related disorders (inflammatory papulopustular acne with scarring, gram-negative folliculitis, and acne rosacea), a reevaluation of isotretinoin aimed at reducing complications is in order. Patient selection criteria and guidelines directed at reducing these complications are presented.
Acne Vulgaris↗
Etomidate and adrenal suppression.
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Adrenal Cortex↗
Mitoxantrone: a replacement for doxorubicin?
Doxorubicin (Adriamycin) is an unquestionably effective anticancer agent for many types of tumors, including advanced breast cancer. However, cardiotoxic effects of the drug have limited its use. Methods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone ( Novantrone ). Mitoxantrone was developed to reduce the cardiotoxicity associated with doxorubicin while maintaining effective antitumoral effects. Initial reports suggested that mitoxantrone might lack cardiotoxic potential; however, recent studies indicate that the drug can produce adverse cardiac effects (congestive heart failure), perhaps with similar frequency to that observed with doxorubicin. It is doubtful that mitoxantrone will be a significant advance over doxorubicin if direct comparative studies reveal a similar incidence of cardiomyopathy.
Anthraquinones↗
Alzheimer's disease: clinical features, pathogenesis, and treatment.
Alzheimer's disease is an insidious degenerative disease of the brain and is the leading cause of dementia in the U.S. Numerous etiologies have been postulated, including a large body of evidence suggesting a slow viral infection, possibly in genetically predisposed individuals, but this remains to be proven. Differential diagnosis is based primarily on exclusion of other treatable forms of dementia. Neurochemical studies suggest a cholinergic deficit; thus primary emphasis in treatment has been directed at enhancing cholinergic activity. Choline and lecithin supplementation generally has been ineffective. Results with physostigmine are encouraging and further studies with this drug prototype are needed. Physostigmine's clinical usefulness is limited, however, due to peripheral side effects and its short duration of action. Other pharmacological approaches, such as naloxone, neural metabolic enhancers, stimulants, and vasopressin analogs, have been investigated. The clinical features and pathology of the disease are reviewed.
Acetylcholine↗
Atracurium and vecuronium: two unique neuromuscular blocking agents.
Atracurium and vecuronium are two new nondepolarizing skeletal muscle relaxants that were developed to overcome the deficiencies seen with currently available agents (tubocurarine, metocurine, pancuronium, and gallamine). Both compounds have unique metabolic profiles, separating them from other nondepolarizing agents. Neither drug depends on normal renal function for excretion and each can safely be given to patients with renal failure. Atracurium also does not depend on hepatic function for metabolism; however, vecuronium may require dosing adjustments in hepatic disease. Atracurium and vecuronium have similar onset times for muscle relaxation but shorter durations of action than other nondepolarizing muscle relaxants. Both agents produce minimal cumulative effects with repeated doses. A major advantage of both agents is their relative lack of cardiovascular effects when given in clinically effective doses, differing from other nondepolarizing muscle relaxants. Both agents produce a lower degree of histamine release than other agents, although atracurium appears to produce a higher incidence of histamine-like reactions than vecuronium. Vecuronium appears to be the agent of choice in patients with a history of asthma or allergy. The place in therapy for these new agents is discussed.
Anesthesia↗
Oral gold in arthritis.
There are few drugs available with purported disease-modifying or healing effects in rheumatoid arthritis. The two agents that have gathered the most support in favor of these effects are parenteral gold and cyclophosphamide; however, both can produce intolerable toxicity. A new oral gold compound (auranofin; Ridaura) is being investigated in rheumatoid arthritis. Available studies suggest that auranofin may be slightly less effective than parenteral gold, but is significantly less toxic, the main side effect being diarrhea. There is evidence to suggest auranofin slows radiologic progression of the disease, but further studies are indicated. If further studies demonstrate a healing effect of the drug, comparable with data suggesting this effect for parenteral gold, auranofin may become a first-line agent in rheumatoid arthritis.
Administration, Oral↗
Transdermal nitroglycerin: a reevaluation.
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Administration, Topical↗
Intravenous streptokinase in acute myocardial infarction.
Intracoronary streptokinase has been reported to be successful in producing coronary recanalization and lowered morbidity and mortality in acute myocardial infarction patients, when administered shortly after the onset of chest pain. However, intracoronary administration of streptokinase is not practical for most hospitals at present, and intravenous administration would enable treatment of larger numbers of patients and enable the drug to be administered earlier than by the intracoronary route. Available studies have suggested benefits of the intravenous route and results of randomized clinical trials indicate an approximately 20-percent decrease in mortality after intravenous use. Intravenous streptokinase after acute myocardial infarction warrants further investigation.
Humans↗
Nifedipine: two new uses.
Nifedipine, a calcium channel blocker currently indicated for vasospastic and chronic stable angina, undoubtedly will have many other uses because of its potent peripheral vasodilatory activity and minimal effects on cardiac contractility. These effects of the drug have proved beneficial in treatment of malignant hypertension and Raynaud's phenomenon. Single oral doses of nifedipine 10-20 mg have rapidly and smoothly reduced blood pressure in malignant hypertension, suggesting its use in the emergency room or office setting. Continuous monitoring of the patient is not required. Studies also have demonstrated the efficacy of nifedipine in Raynaud's phenomenon, and the drug should be considered as an initial agent of choice.
Humans↗
Therapy of syndrome malin.
Syndrome malin refers to neuroleptic malignant syndrome (NMS), a combination of extrapyramidal symptoms, hyperthermia, autonomic dysfunction, hypertension, and coma, which has been reported primarily with haloperidol administration, but also with fluphenazine, thiothixene, and thioridazine. NMS is much more severe than typical extrapyramidal reactions to neuroleptic agents and can result in fatality. The syndrome is not dose related and can begin within hours of initiation of therapy or after months of treatment. Treatment of NMS has been mainly supportive in the past. Recent reports have suggested benefits from the use of bromocriptine and amantadine (dopaminergic agonists), based on a possible etiology of neuroleptic-induced dopaminergic blockade. Dantrolene also has been utilized successfully in NMS on the hypothesis that the syndrome is similar to anesthetic-induced malignant hyperthermia. These agents provide a more specific treatment for this potentially lethal syndrome.
Antipsychotic Agents↗
Treatment of bulimia.
Bulimia (bulimia nervosa; binge eating) is characterized by episodic eating of large amounts of food, followed by self-induced vomiting or laxative abuse. Psychotherapy has been the mainstay of treatment and often has been unsuccessful. The similarity of bulimia to major depression has led to evaluation of antidepressant drugs for treatment of the disease. Imipramine has proven effective in reducing binging episodes, and further evaluation of antidepressants seems warranted. Phenytoin also has been effective in some cases, suggesting that bulimia may be a neurologic disorder analogous to epilepsy. Optimal treatment may be antidepressants combined with a nutrition/psychotherapy program.
Adolescent↗
Indapamide: a unique diuretic?
Indapamide (Lozol) is a new diuretic and antihypertensive agent. The drug appears to have a unique mechanism of action, combining diuretic effects with a direct vascular action, presumably secondary to calcium channel blockade. Available studies indicate that indapamide is comparable to hydrochlorothiazide, chlorothiazide, furosemide, and other diuretic agents in the management of hypertension and edema. The drug produces toxicity similar to that of the thiazide and loop diuretics; however, it does not appear to increase cholesterol levels. Although it is claimed that indapamide produces no effect on glucose levels, hyperglycemia has been reported. Indapamide is safe and effective for treatment of hypertension in mild to severe renal impairment, but advantages over furosemide are questionable. Indapamide is a unique diuretic, but does not appear to offer advantages over other available agents.
Antihypertensive Agents↗
Comparison of alphabetic and phonetic retrieval of online drug information.
Alphabetic, phonetic, and combined alphabetic and phonetic methods of retrieving online drug information were compared. Twenty-four volunteers participated in the study representing four user groups: physicians, nurses, pharmacists, and nonhealth-care hospital staff. Each subject performed 150 searches, 50 by each retrieval method. Using the alphabetic method, drug information was retrievable only if the drug name was spelled correctly. Using the phonetic method, searches were conducted based on the phonetic spelling of requests (e.g., "symetadine" for cimetidine). The combined method used a phonetic search only after an initial alphabetic search was unsuccessful. The elapsed time between the first entry and an indication that the information had been found or could not be found was determined, and the number of drug names not found and the number of excess tries were counted. There were no significant differences in elapsed time among the three methods. Pharmacists had the shortest mean elapsed time and physicians the longest. The average number of excess tries using the phonetic system was a third of the number required using the alphabetic method. The number of drugs not found showed only slight differences among the three methods. The subjects found the desired information on the first try 67% of the time with the alphabetic method, 66% with the combined method, and 90% with the phonetic method. The phonetic method had an average of 75 matches versus 20 for the alphabetic and combined methods. These results support use of a combined alphabetic and phonetic system for retrieving drug information.
Drug Information Services↗