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At least 19 recordsLinked to original sources
PubMed1976

[Cutaneous side effects of systemic drugs. Part 4 of a synopsis. 6/7. Drugs affecting the central nervous system. C. Drug-induced photosensitivity. D. Drug-induced changes of skin color].

This, the fourth part of a synopisis of cutaneous side effects of drugs, covers the drugs affecting the central nervous system: antiepileptics, hypnotics, narcotics and psychopharmaceutics; the myorelaxants and antiallergics follow, and lastly there is a section on drug addiction and placebo. The various cutaneous side effects are listed in chart form referring to more than 500 sources. A drug index is attached for handy reference. The reviews of certain drug induced skin disorders are continued with tables covering photosensitivity and changes in skin colour. Phototoxicity, photoallergy and light sensitivity by porphyria are differentiated. The various pigmentation disorders, colour changes due to metal deposits as well as different localisations are included.

Anticonvulsants↗
PubMed2026

Anti-psychotic drugs act synergistically in combination with antifungal drugs to inhibit drug-resistant Cryptococcus neoformans and Candida albicans.

UNLABELLED: Systemic fungal infections cause an estimated 3.8 million deaths annually, approximately 10% of which are caused by drug-resistant infections. With only five classes of antifungal drugs, treatment options are limited. Here, we explore synergistic drug combinations-when the efficacy of two drugs combined is greater than expected based on the sum of each individual drug's efficacy-to improve treatment of drug-resistant Cryptococcus neoformans and Candida albicans. Chlorpromazine acts synergistically with both amphotericin B and fluconazole against multiple fungal species, including azole-resistant C. neoformans and C. albicans. We then performed a genome-wide knockout mutant screen and found that ESCRT pathway mutants are resistant to chlorpromazine, while knockout mutants of genes involved in fatty acid biosynthesis are sensitive. Based on these data, we investigated sterol and fatty acid composition in chlorpromazine-treated cells and found only minor increases in sterol precursors, but a substantial increase in lipid droplet size and decreased lipid droplet numbers. This lipid droplet formation potentially sequesters lipid bioavailability and response to membrane stress. Together, these data suggest that chlorpromazine and its analogs are potentially promising treatments for systemic fungal infections that act via lipid homeostasis and stress response. IMPORTANCE: Fungal infections are a large and expensive health burden with high mortality rates. People with compromised immune systems from cancer, solid organ transplant, HIV infection, and other conditions are particularly affected. Systemic fungal infections are difficult to treat because there are few available drugs and treatment periods last months or years. Long treatment times increase the risk of treatment failure and can contribute to the rise of resistance. We identified an additional class of drugs, chlorpromazine and other phenothiazine drugs, that amplify the activity of existing antifungal drugs amphotericin B (AmB) and fluconazole (FLZ). AmB and FLZ act by targeting ergosterol, the fungal equivalent of cholesterol, which is required for a functional plasma membrane. Chlorpromazine increases the formation of lipid drops, which sequester lipids such as ergosterol. When chlorpromazine is combined with AmB, the fungal cell cannot respond to the plasma membrane damage caused by AmB, inhibiting the fungal cells. This work identifies new target processes and drugs that could treat deadly fungal infections.

antifungal resistance↗
PubMed1979

Drug effects on the liver: a tabular compilation of drugs and drug-related hepatic diseases.

Geneic and chemical names of drugs and the possible adverse effects of these drugs on the human liver were tabulated. All drugs compiled in these tables have been approved by the Federal Drug Administration. They are currently available in the United States, and they are listed in the 1979 Physicians' Desk Reference. The tables include: (1) names of drugs that have caused a characteristic morphologic change, such as cholestatic lobular hepatitis; (2) morphologic diagnoses that have been documented after administration of each drug; and (3) references that can be matched to each drug and to its effects on the liver.

Chemical and Drug Induced Liver Injury↗
PubMed1976

Assessment of drugs in schizophrenia. Asessment of drug-induced extrapyramidal reactions and of drugs given for their control.

I have tried to bring out some of the important methodological problems found in examining the effectiveness of drugs used in the control of druginduced parkinsonism by referring mainly to studies in which I have taken part. I hope I have shown that the whole topic is far less well understood than is often assumed. The main points may be summarized as follows: there is doubt as to whether many of the drugs used in controlling drug-induced parkinsonism are really effective; the results of many studies are conflicting; many studies contain serious flaws in design; methods for assessing extrapyramidal signs are not well developed; we are ignorant of the way in which drug-induced extrapyramidal signs change spontaneously. There is a clear need for further research in this area to improve techniques of assessment, to provide basic information on drug-induced syndromes, and to rigorously examine the efficacy of the drugs used in controlling them.

Amantadine↗
PubMedDate not supplied

The metabolism of drugs in isolated rat hepatocytes. A comparison with in vivo drug metabolism and drug metabolism in subcellular liver fractions.

The metabolism of drugs in isolated rat hepatocytes has been investigated. Drugs which are metabolized by aromatic hydrolation, aliphatic hydroylation, N-demethylation, or glucuronidation have been used as substrates. With some substrates the rate of metabolism in isolated hepatocytes compares with that in hepatic 900g supernatant fraction or microsomes, but other substrates are metabolized at a slower rate in isolated hepatocytes. For example, the rate of butamoxane hydroxylation in isolated hepatocytes is slower than that in microsomes. However, the rate of hydroxylation is hepatocytes is identical to that in perfused liver. The metabolism of drugs in isolated hepatocytes correlates with in vivo drug metabolism better than does metabolism in the hepatic 9000g supernatant fraction or microsomes.

Animals↗
PubMed1977

Drug resistance and plasmid mediated transfer of drug resistance in Escherichia coli isolated from various districts of the human organism. A possible relationship with the antimicrobial drug concentrations during therapy.

The study of the prevalence of drug resistances and of the frequency of R factors among resistant strains, in E. coli isolated respectively from the respiratory, intestinal and urinary tracts of patients, during 1976, has shown that the frequency of drug resistances is highest among E. coli strains isolated from the respiratory tract and lowest among the E. coli strains isolated from urines. The frequency of R factors, among resistant strains, follows an exactly opposite distribution. This behaviour could be related to the gradient of antimicrobial drug concentrations achieved in the various compartments during ordinary antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed1979

Developing drug-use profiles from drug-charge records.

The potential for developing a drug-use profile from drug-charge records was studied at an 830-bed community hospital. Patient drug charges were reviewed retrospectively for one year (1975) to identify: (1) which key drugs accounted for a high percentage of cost and usage; (2) where key drugs were used within the hospital; (3) how they were used; and (4) who were the chief prescribers. Of the drugs used, 8% accounted for 80% of total drug product costs. Seven drug groups (10% of the total drug groups) appeared in the top 10 of both drug cost and quantity categories. Six individual drugs also appeared in the top 10 of both categories. According to cost, cephalosporin antibiotics were ranked first among drug groups but were sixth according to quantity. Analgesics-antipyretics were ranked first among drug groups by quantity and second by cost. Cephalothin was ranked first among individual drugs by cost and was not in the top 10 in quantity. Diazepam was ranked first among individual drugs by quantity and third by cost. Patients' drug-charge records can be used effectively to generate drug-use profiles for ongoing drug use review, quality assurance and cost containment programs.

California↗
PubMed1976

Renal failure, drug pharmacokinetics and drug action.

Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.

Drug Administration Schedule↗
PubMedDate not supplied

Drug-drug interactions among residents in homes for the elderly: a pilot study.

This pilot study investigated epidemiologically the potential for clinically significant drug-drug interactions, a subclass of adverse drug responses, in two homes for the elderly. The agent (drugs), host (residents), and environment (rural and urban nursing homes) in the illness known as drug-drug interaction were studied. Drug profiles on 188 subjects were compiled and screened by computer. Of these, 100 (80 in the rural home and 20 in the urban home) had the potential for clinically significant drug-drug interactions. Laboratory diagnostic procedures essential to confirm the unintentional interaction of two or more drugs were beyond the scope of the study; therefore, physicians independently reviewed the records of 66 residents who could be interviewed, agreeing that 27 residents were potential drug-drug interactors. These subjects had twice as many drug products and three times as many pro re nata products prescribed for them as did subjects without the potential for drug-drug interaction. The possible cause of interaction found most frequently was digitalis combined with thiazide or furosemide. The results of this pilot study suggest several implications for practice within the research setting.

Aged↗
PubMed1978

Drug therapy reviews: clinical pharmacology of antiepileptic drugs.

The absorption, distribution, biotransformation, excretion and clinical pharmacokinetics of antiepileptic drugs are reviewed. Six guidelines for the therapeutic use of these drugs are given: (1) when therapy with an antiepileptic drug is initiated or when dosage is raised or lowered, the new steady-state drug serum concentration and the full effect of the dosage change will not occur for five elimination half-lives; (2) a loading dose is usually necessary to immediately achieve a steady-state serum drug concentration equal to the usual maintenance steady-state serum drug concentration; (3) the choice of dosage intervals for antiepileptic drugs is determined in part by the range of fluctuation in drug concentration between doses that is acceptable; (4) addition of a drug to an existing antiepileptic regimen may raise or lower the serum concentration of prior drugs by inhibition or induction of their metabolism; (5) if possible, make only one change at a time in an antiepileptic drug regimen; and (6) antiepileptic drugs should not be given by the i.m. route in emergency situations.

Absorption↗
PubMed1979

Constraints of drug regulation on the development of new drugs.

A review is given of the various regulations for the preclinical and clinical evaluation of new drugs, their effects on the clearance of new medicines for general use by practising physicians, and their repercussion on industrial drug research. Undoubtedly, extensive and continuously increasing regulatory procedures, which in addition have to be satisfied repeatedly in individual countries, claim an unproportionally high percentage of the industrial capacity for research and development of new drugs, leaving too little for basic research, which is a prerequisite for the discovery of new medicines that are more than just "me too" products. Despite the fact that regulatory language differs from scientific attitude and arguments, the wall of regulations should be neither too thick nor too high to impede research and to hinder the prompt application of important new drugs. Even the most sophisticated and extensive drug regulations cannot prevent the use of drugs which is not indicated, because it is impossible to regulate ignorance. To regulate drugs is necessary, but the governments and their drug agencies should also encourage drug research and should support industry in the development of new drugs. On the other hand, the drug companies must adhere to the accepted standards and create an atmosphere of confidence by presenting reliable and complete data.

Drug Industry↗
PubMed2026

Surveilled subjectivation: narratives of drug policing among people who use prohibited drugs in Sweden.

In Sweden, possession and personal use of drugs are criminalized since 1988, resulting in police work being directed towards minor drug offenses. Despite this, police and other authorities are encouraged to protect the health and wellbeing of people who use prohibited drugs (PWUPD). Knowledge is scarce on how this drug policy plays out in practice. This study therefore analyzes interviews with 20 PWUPD who visited harm reduction services and interacted with policing agents in Stockholm, Sweden. The analysis is based on the participants' narratives of drug policing, and it concerns how they produced themselves as subjects through relations between materiality and discourse. We utilize the concept of surveilled subjectivation to elucidate what the participants could do, what they knew and who they could be or become under drug policing. Four themes were identified illustrating the link between discourse and materiality in PWUPD's surveilled subjectivation: "Material aspects of surveillance"; "Resisting the 'drug abuser' identity"; "Fighting power with power"; and "Crossing boundaries and becoming-other". The participants described nonstop efforts to prevent their bodies, activities, belongings and environments from being enfolded by drug law enforcement, which otherwise would fuel even more surveillance. They therefore disassociated themselves from the "drug abuser" identity, and managed encounters with policing agents by keeping a low profile or acting compliantly. While the study highlights the skills and knowledges the participants deployed to navigate omnipresent drug policing, we conclude that their production of autonomous and empowered subjectivities would be facilitated if possession and use of drugs were no longer criminalized.

Humans↗
PubMed1976

[Drug-drug interactions (author's transl)].

This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field.

Age Factors↗
PubMed1977

Comparison of ethanol, pentobarbital, and phenobarbital using drug vs. drug discrimination training.

Rats learned drug vs. drug (D vs. D) or drug vs. no drug (D vs. N) discriminations in a T-maze shock escape task with various doses of pentobarbital, phenobarbital, or ethanol. Dose-effect curves were obtained for each drug using D vs. N training. After D vs. N training with any one of these drugs, rats made D choices during substitution tests with the other two drugs, suggesting drug interchangeability. D vs. D training also showed that pentobarbital and phenobarbital were virtually indistinguishable from one another. However, ethanol was readily discriminated from pentobarbital, showing that the two drugs differed. The results show the utility of D vs. D training as a method for studying drug differences that may be too small to detect with substitution tests.

Animals↗
PubMed1979

[Drugs and acute agranulocytosis: analysis of previous drug intake in 42 patients (author's transl)].

An exact account of previous drug intake was obtained in 42 patients with acute agranulocytosis. Because of the multiplicity of administered drugs, often in the form of multiple-drug preparations, it was possible in only a minority of cases to ascribe with any degree of certainty a causative role to any particular drug. But outstanding as possible causes were thyrostatic drugs and pyrazolone. But no conclusion could be drawn as to the incidence of agranulocytosis with regard to these drugs because of the absence of data on the frequency that they are prescribed and the unknown number of fatal cases of agranulocytosis. The results indicate that multiple drug treatment and in particular the unnecessary prescribing of multiple-drug preparations makes it difficult to ascertain side-effects of drugs. They once again point to the need of frequent checks of white cell count in the drug treatment of pyrexial diseases.

Acute Disease↗
PubMed1976

[The value of the thrombocytopenia test in the specific diagnosis of drug allergy, especially drug-exanthema].

125 thrombocytopenia tests (so-called thrombocytopenic index) from 94 patients with suspected drug allergies and negative skin tests were critically examined to determine the value of this in vivo method in the clarification of drug allergy. A consistent decrease of 20% or more in thrombocytes was rated as significant and therefore indicative of drug sensitization. 78.4% of the tests were in agreement with the expected result. Clinically relevant drug sensitivity was apparent in 30.4% of the tests, while the possibility of allergy could be eliminated in 48%. 16.8% of the results were inconclusive and 4.8% were false negatives. A flare-up occurred after 5.6% of the tests. A leukocyte count was considered unnecessary since it proved to be unrelated to a drop in thrombocytes and the existence of drug allergy. The thrombocyte test is a practical and valuable method for investigation of drug allergies, especially as the available in vitro tests are too complex to be used routinely in a diagnostic test program. However, the results must be considered critically in conjunction with an accurate case history, the clinical symptoms and the course of the disease. In the case of blisters and erythema exsudativum multiforme-like drug exanthema, renewed exposure to the suspected drug must be avoided due to the possible danger of a drug reaction. The latest research results have helped to clarify the underlying mechanism of the thrombocyte decrease.

Aspirin↗
PubMed1978

Conjugation of methotrexate to poly(L-lysine) increases drug transport and overcomes drug resistance in cultured cells.

Methotrexate and [(3)H]methotrexate were conjugated through a carbodiimide-catalyzed reaction to a 70,000 molecular weight poly(L-lysine) in molar ratios of approximately 13 to 1. The cellular uptake of labeled conjugate was far in excess of the uptake of free drug in cells that were either proficient or deficient in methotrexate transport. The conjugate markedly inhibited the growth of PRO(-)3 Mtx(RII) 5-3 Chinese hamster ovary cells, which are known to be drug resistant by virtue of a deficient methotrexate transport. The cells, however, were not inhibited by the same concentrations of free poly(Lys) and free drug. The 100-fold difference in drug concentration needed to inhibit the mutant cells and their corresponding wild type was totally abolished by exposing the methotrexate-resistant cells to methotrexate-poly(Lys). That the drug is carried into the resistant cells as intact drug-poly(Lys) is evident also from the fact that the conjugate is rendered inactive by brief trypsinization in vitro. Because the conjugate fails to inhibit dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP(+) oxidoreductase; EC 1.5.1.3) in vitro, it must be concluded that the strong growth inhibitory effect of the conjugate is due to the intracellular hydrolysis of its polymeric backbone, followed by the release inside the cell of a pharmacologically active form of methotrexate. Our date show that in methotrexate-resistant cells the intracellular release of active drug after uptake of conjugate is of the same order of magnitude as the uptake of free drug by transport-proficient cells and, hence, that the drug resistance due to deficient transport can be totally overcome.

Biological Transport↗