Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DRUGS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2005

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

Antibiotics, Antineoplastic↗
PubMed2000

[Unwanted drug interaction between anti-arrhythmic drugs and drugs used for heart failure].

The appearance of adverse drug reactions may depend on the category of used drugs as well as on the coexistence of a pathological stage. Clinically important are: interactions of digitalis glycoside drugs leading to the occurrence or intensification of toxic symptoms characteristic for those drugs; interactions of antiarrhythmic drugs which may cause proarrhythmic effects and hypotension, and also interactions of nitrates resulting in lowering of the blood pressure. Quinidine, verapamil, nitrendipine, amiodaron, propafenone, captopril, spironolactone decrease renal clearance of digoxin, and amilorid/triamteren lower the extrarenal clearance of this drug. Thus the outcome of those concommitant therapies is the increase of digoxin serum concentration and appearance of toxic symptoms. Clinically dangerous, in the course of the antiarrhythmic therapy, is the increased risk of the arrhythmia appearance when two or more antiarrhythmic drugs are applied concomitantly. Antiarrhythmic drugs class IA (quinidine, disopyramide), class III (sotalol, amiodarone), class IV (calcium channel blockers) used at the same time with potassium depleters diuretics or beta-blocking agents result in the inhibition of repolarization and the increased duration of activation potential with the risk of developing arrhythmia of the torsade de pointes types. Nitrates interactions are mainly of the pharmacodynamic character. Most common adverse drug reaction, observed during the concomitant nitrates and another circulatory drug therapy, is excessive lowering of the blood pressure. These may lead to the decrease in the therapeutic efficacy of these combinations. Interactions of circulatory drugs are numerous, sometimes difficult to predict and they may lead to the intensification of the adverse drug reaction and lowering of their therapeutic efficacy.

Anti-Arrhythmia Agents↗
PubMed2004

Drug interaction ontology (DIO) for inferences of possible drug-drug interactions.

Drug Interaction Ontology (DIO) was developed for formal representation of pharmacological knowledge. It provides a fundamental framework for accumulation of reusable knowledge components in molecular pharmacology. Ontology was employed and implemented as a relational model. Some features include: 1) Drug-biomolecule interaction was assumed as a primitive knowledge element. 2) Symbolic representation was developed for drug-biomolecule interaction. Consequences of two conjugated units of interaction were defined by using symbols. These are applied for query development for identification of possible drug-drug interaction. 3) The triadic relationship model was developed as a ground model for bio-logical interactions and/or function, including semantic ones. One application of DIO is to support hypothesis generation of drug interaction by providing new hypotheses from a structured database storing literature information on known drug-biomolecule interactions. A knowledge base using DIO that contains information beginning with anti-cancer drugs is now under development. Detection of possible drug interaction was tested and its capacity to lead clinically known ones was confirmed. The system generated theoretically possible drug-drug interactions, which implies potential usefulness of new drugs to be tested before actual clinical application. In this paper, sorivudine and 5-fluorouracil mediated by dihydropyrimidine dehydrogenase are presented.

Arabinofuranosyluracil↗
PubMed2000

Dose staggering as a strategy to reduce drug--drug interactions due to reversible enzyme inhibition between orally administered drugs with high first pass effect: a computer simulation study.

A physiological computer model was designed to simulate the metabolic drug-drug interactions between two orally co-administered drugs due to reversible enzyme inhibition using drug concentrations in the portal vein. The extent of interactions was compared at steady-state for the effects of a delay in time between the administration of the substrate and the inhibitor. It was demonstrated that the extent of the interactions can be strongly affected by a time interval between the two drug administrations. By delaying the administration of the inhibitor until after the absorption phase of the substrate, one can significantly reduce the extent of the drug--drug interactions. This is because drug concentrations in the portal vein and the liver are much higher than that in the systemic circulation during the absorption phase. The model also showed that interactions involving substrates with a high extraction ratio (E(H)), i.e., drugs with higher first-pass effect, can be more strongly affected by dose staggering. Substrates with a low absorption rate constant (k(a)) require a longer interval with the inhibitor in order to reduce the extent of the interactions. This observation suggests dose staggering as a simple and cost-effective way to reduce the extent of unwanted drug--drug interactions in clinical practice.

Administration, Oral↗
PubMed1993

The economic context of drug and non-drug reinforcers affects acquisition and maintenance of drug-reinforced behavior and withdrawal effects.

The focus of this review is to examine the effect of non-drug alternative reinforcers on drug-reinforced behavior. An increasing number of animal laboratory as well as human clinical studies have demonstrated the effectiveness of non-drug reinforcers in reducing steady-state levels of drug self-administration. One goal of this review was to determine what behavioral economic conditions are optimal for reducing drug-reinforced behavior. Variables such as price of the drug and non-drug reinforcer have been manipulated by changing fixed-ratio (FR) value of these commodities. Income has been changed by limiting the amount of access to the commodities or by changing session length. Substitution was evaluated by determining whether decreased demand for a drug (due to increased price) was related to increased demand for a non-drug reinforcer. A second goal of this review was to investigate transition states in the drug addiction process with respect to the role of alternative non-drug reinforcers. Animal models of acquisition and withdrawal were examined to identify behavioral economic conditions under which acquisition may be prevented or withdrawal effects (and potential for relapse) may be alleviated.

Animals↗
PubMedDate not supplied

Retrospective drug utilization review: incidence of clinically relevant potential drug-drug interactions in a large ambulatory population.

OBJECTIVE: To determine the incidence of clinically relevant potential drug-drug interactions (DDIs) in a large population of ambulatory patients utilizing a computerized, retrospective drug utilization review (DUR) program followed by clinical pharmacist audit. METHODS: The drug claims database included approximately 2.9 million patients with more than 30 million prescriptions dispensed in the 12-month period from September 2001 through August 2002. Cases were identified by a computerized, retrospective DUR program with embedded triggers to detect 69 prespecified potentially serious DDIs, with "serious" defined as an interaction that would likely require a change in therapy or use of additional clinical or laboratory monitoring. Two types of automated, computerized assessments were conducted: the first simply detected coprescribed drug pairs, and the second assessment used more sophisticated filters to reduce false positive alerts for coprescribed drug pairs. Clinical pharmacist audit then determined the final incidence of clinically relevant warnings; in this audit, coprescribed drug pairs were defined as clinically relevant if they could cause potentially serious DDIs. RESULTS: Eighteen drug pairs had insufficient cases for inclusion, leaving 51 drug pairs for evaluation. A total of 244,703 cases of potential DDIs were identified (0.8% of total prescription claims) by simple automated screens. More sophisticated DDI filters reduced the 244,703 potential DDIs by 70.8%, to a total of 65,544 pairs (0.2% of total prescription claims). Clinical pharmacist review reduced the number of potential DDIs by an additional 80.6%, to 12,722 drug pairs (0.04% of total prescription claims) deemed clinically relevant. The combination of sophisticated DDI filters and clinical pharmacist review reduced the incidence of potentially serious DDIs by 94.3%. CONCLUSION: The incidence of potentially serious DDIs is relatively low (less than 1%) among ambulatory patients; however, the incidence depends on the method of case finding. Retrospective DUR programs, especially those with additional automated filters or that utilize additional pharmacist review, appear to be important screening tools in determining true rates of coprescribed drug pairs that can lead to potentially serious DDIs.

Ambulatory Care↗
PubMed1987

Drug findings in 'Driving Under the Influence of Drugs' cases: a problem of illicit drug use.

Drug findings in 137 drug positive cases of Driving Under the Influence of Drugs (DUID) occurring in St. Louis, Missouri, U.S.A. from June 1983 through May 1986 are presented. Thirty-two different drugs were detected. A single agent was detected in only 34% (47/137) of cases. The most frequently encountered drugs, expressed as percent of positive cases, were: phencyclidine, 47%; marijuana, 47%; benzodiazepines, 22%; barbiturates, 15%; opiates, 11%; and cocaine, 9%. Most multiple drug cases involved popular illicit drug mixtures, such as cocaine and morphine (speedballs) or phencyclidine on marijuana (whack). All the drivers in this survey had displayed inappropriate or impaired operation of a motor vehicle to the extent that a law enforcement officer had stopped and charged them for DUID. In at least 81% of the drug positive cases, persons impaired in the operation of a motor vehicle from a drug or drugs other than alcohol, were impaired not as the result of side effects of therapeutic drug use, but as the result of deliberate self intoxication with illicit or controlled substances.

Automobile Driving↗
PubMed2003

Adverse drug reaction monitoring in Jena. Relevance of polymorphic drug metabolizing enzymes for inducing adverse drug reactions.

Inter-subject variability in therapeutic drug response and drug toxicity is a major problem in clinical practice. In this field genetic polymorphisms of drug metabolizing enzymes play an important role. In a multicenter study supported by the German Federal Institute for Drugs and Medical Devices (BfArM, Z 12.01-68502-201) adverse drug reactions (ADRs) leading to hospital admission to departments of internal medicine have been registered and evaluated. The aim of the presented part of the study was to look for evident differences in genotypes for polymorphic drug metabolizing enzymes between adverse drug reaction cases and controls. All cases found in the local area--Jena and Weimar--were genotyped for N-acetyl-transferase 2 (NAT2), cytochrom P450 (CYP) 2D6 and 2C19 in comparison to a control population of the same region. The investigation on genotype was carried out for about 2 years (2000-2002). 254 blood samples from patients of the ADR study were analyzed. The genotype of drug metabolizing enzymes was determined by means of polymerase chain reaction using allel specific primers or restriction enzyme analysis. Within all ADRs cases genotyped, no exceptional frequencies for slow acetylators or poor metabolizers (PM) of CYP2D6 or CYP2C19 were found. About 65% of the individuals with ADR genotypically displayed a slow acetylator state. 6.3% PM for CYP2D6, including CYP2D6*3, *4 and *6 alleles, and 2.0% PM frequency for CYP2C19 (*2) have been found in ADR cases. A direct connection between PM genotype and the ADR observed may be assumed only in few of them. Further investigations on genotype and ADR-associated drugs require a much larger sample of patients to obtain more data allowing to focus an association on specific drugs, ADR and polymorphisms genotype of drug metabolizing enzymes might be useful.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Predicting inhibitory drug-drug interactions and evaluating drug interaction reports using inhibition constants.

OBJECTIVE: To review the use of inhibitory constants (Ki) determined from in vitro experiments in the prediction of the significance of inhibitory drug-drug interactions (DDIs). DATA SOURCES: Searches of MEDLINE (1966-August 2004) and manual review of journals, conference proceedings, reference textbooks, and Web sites were performed using the key search terms cytochrome P450, drug-drug interaction, inhibition constant, and Ki. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and information deemed relevant was included for this review. DATA SYNTHESIS: The cytochrome P450 isoenzymes factor prominently in the explanation of numerous DDIs. Although the regulation of these enzymes by one drug can affect the pharmacokinetics of other drugs, the consequences may not necessarily be significant either in terms of pharmacokinetic or clinical outcomes. Yet, many DDI monographs originate as unconfirmed case reports that implicate the influence of one drug on the CYP-mediated metabolism of another, and these often uncorroborated mechanisms can eventually become regarded as dogma. One consequence of this process is the over-prediction of potentially important DDIs. The pharmaceutical industry, Food and Drug Administration, and pharmaceutical scientists have developed a strategy for predicting the significance of inhibitory DDIs at the earliest possible stages of drug development based on a new chemical entity's Ki value, determined in vitro. CONCLUSIONS: We suggest that the use of Ki values of drugs purported to behave as CYP inhibitors be incorporated in the assessment of case reports that ascribe DDIs to inhibition of metabolism of one drug by another.

Area Under Curve↗
PubMed1997

Newer anticonvulsant drugs: role of pharmacology, drug interactions and adverse reactions in drug choice.

In the last few years a number of new anticonvulsants have been introduced into clinical practice mainly as add-on therapy in patients who do not become seizure-free while receiving established anticonvulsants. Up to now, no single drug has been shown to be more effective at controlling seizures of a particular type than another, so other factors such as mechanism of action, pharmacokinetics, dosage regimens or the spectrum of adverse drug reactions and interactions are used when making a choice between one agent and another. The mechanism of action of tiagabine and vigabatrin is very specific; both agents increase gamma-aminobutyric acid (GABA) levels through inhibition of reuptake and catabolism respectively. However, the mechanism of action of gabapentin is unknown and those of felbamate, lamotrigine and topiramate are not sufficiently clarified as yet, and may be multiple. Great advances have been made in improving the pharmacokinetic characteristics of these newer anticonvulsants. Gabapentin and vigabatrin exhibit relatively ideal pharmacokinetic properties as they are not bound to proteins, are excreted mostly unchanged in the urine and show linear pharmacokinetics. Lamotrigine possesses a highly variable elimination half-life depending on the co-medication. Tiagabine is highly protein bound and zonisamide shows nonlinear pharmacokinetics; both these drugs are extensively metabolised. Problematic drug interactions between newer anticonvulsants and other drugs in general occur rarely when these agents are given concomitantly. However, in common with most new drugs, there are very few data on the use of the newer anticonvulsants in women of childbearing age. Studies done so far on interactions with oral contraceptives used low anticonvulsant dosages for a very short time. The newer anticonvulsants elicit adverse reactions that, while not being unique, are particularly associated with that drug. For example, felbamate may cause aplastic anaemia and fulminant liver failure, lamotrigine is prone to cause skin rash, and oxcarbazepine may cause symptomatic hyponatraemia. Topiramate and zonisamide cause kidney stones, and vigabatrin may induce psychiatric syndromes. Although highly diverse in structure and activity, these newer drugs offer new possibilities for treating refractory epilepsy. However, since no single factor can dictate the choice of drug nor predict the success of treatment, prescribing of these rather expensive drugs has to depend upon careful consideration of the aims of treatment, the characteristics of the drug and the needs of the individual patient.

Adult↗
PubMed2003

Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interaction between quinolones and anti-inflammatory drugs.

Quinolones have been reported to possess potent convulsant activity, which is enhanced when they are administered concurrently with anti-inflammatory drugs. To define the individual drug interactions of quinolones with anti-inflammatory drugs, we studied the convulsant activity of six quinolones with or without 13 anti-inflammatory drugs and 3 analgesic/antipyretic drugs in mice. Intraventricular injections of norfloxacin (NFLX), enoxacin (ENX), ciprofloxacin, lomefloxacin (LFLX), levofloxacin, and gatifloxacin induced convulsions in mice in a dose-dependent manner. Concurrent administration of biphenylacetic acid strongly enhanced the convulsant activity of NFLX, ENX, and LFLX. Flurbiprofen also strongly enhanced the activity of NFLX and ENX, and ketoprofen strongly enhanced the activity of ENX. However, mefenamic acid, piroxicam, tenoxicam, meloxicam, etodolac, sulpyrine, isopropylantipyrine, and acetaminophen had no effect on the convulsant activity of quinolones. These results suggest that each quinolone has an individual drug interaction with each anti-inflammatory drug. It was suggested that we should know which anti-inflammatory drugs enhance the convulsant activity of individual quinolones, and which quinolone has no/weak drug interaction with different anti-inflammatory drugs when these drugs are used concurrently for the treatment of patients with infectious diseases.

Animals↗
PubMed2000

Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG-anhydride-drug linkages.

We have designed a new mucoadhesive drug delivery formulation based on H-bonded complexes of poly(acrylic acid) (PAA) or poly(methacrylic acid) (PMAA) with the poly(ethylene glycol) (PEG), of a (PEG)-drug conjugate. The PEGylated prodrugs are synthesized with degradable PEG-anhydride-drug bonds for eventual delivery of free drug from the formulation. In this work we have used indomethacin as the model drug which is PEGylated via anhydride bonds to the PEG. The complexes are designed first to dissociate as the formulation swells in contact with mucosal surfaces at pH 7.4, releasing PEG-indomethacin, which then hydrolyses to release free drug and free PEG. We found that as MW of PAA increases, the dissociation rate of the complex decreases, which results in decreased rate of release of the drug. On the other hand, the drug release from PEG-indomethacin alone and from solid mixture of PEG-indomethacin+PAA was much faster than that from the H-bonded complexes. Due to the differences in the thermal stability, PMAA complex exhibited slightly faster drug release than that of the PAA complex of comparable MW. These H-bonded complexes of degradable PEGylated drugs with bioadhesive polymers should be useful for mucosal drug delivery.

Acrylic Resins↗
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↗
PubMed1983

The drug-consuming patient and his drugs. II. The drugs.

The drug consumption pattern and patients' knowledge about their drugs have been studied in 506 patients, acutely admitted to hospital. The patients took a mean of 3.2 drugs before hospitalization, the majority of them being used for more than one year. Calculated on all 506 interviewed patients, women took more drugs than men, but among the 406 users there was no significant difference in the number of drugs taken by men or women. The number of drugs increases markedly with age. The drugs most commonly used were digoxin (30% of the patients), nitrazepam (19%), furosemide (18%), potassium (17%) and nitroglycerin (14%). Dosage reduction with advancing age was registered i.a. for digoxin. Judging from the number of adverse drug reactions (ADRs) and subjective side-effects, the dosage reduction should probably have been even greater. Twenty-six patients (5%) were admitted because of an ADR, another 10 (2%) with an ADR. For the majority of drugs (84%) the patients had some understanding of the expected effect, but knowledge about possible side-effects was reported for 26% of the drugs only.

Acute Disease↗
PubMed2003

Dissemination of information on potentially fatal adverse drug reactions for cancer drugs from 2000 to 2002: first results from the research on adverse drug events and reports project.

PURPOSE: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug-associated adverse drug reactions (ADRs) reported in the postmarketing setting. METHODS: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed. RESULTS: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period. CONCLUSION: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Drug-drug interaction studies on first-line anti-tuberculosis drugs.

The purpose of this study was to carry out drug-drug compatibility studies on pure first line anti-tuberculosis drugs, viz., rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol hydrochloride (E). Various possible binary, ternary, and quaternary combinations of the four drugs were subjected to accelerated stability test conditions of 40 degrees C and 75% relative humidity (RH) for 3 months. For comparison, parallel studies were also conducted on single drugs. Changes were looked for in the samples drawn after 15, 30, 60, and 90 days of storage. Analyses for R, H, and Z were carried out using a validated HPLC method. The E was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), as it does not absorb in ultraviolet (UV). All single pure drugs were relatively stable and showed only 3%-5% degradation under accelerated conditions for 3 months. However, significant interactions were observed in case of the drug mixtures. In particular, ternary and quaternary drug combinations containing R and H along with Z and/or E were very unstable, showing 90%-95% and 70%-75% loss of R and H, respectively. In all these cases, isonicotinyl hydrazone (HYD) of 3-formylrifamycin and H was found to be the major degradation product. In case of RE and RZE mixtures, where H was absent, 3-formylrifamycin was instead the key degradation product. Another unidentified peak was observed in the mixture containing RZE. Apart from these chemical changes, considerable physical changes were also observed in pure E and the mixtures containing E, viz., RE, ZE, RHE, RZE, and RHZE. In addition, significant physical changes associated with noteworthy loss of H and E were also observed in mixtures containing HE and HZE. The present study thus amply shows that the four primary anti-tuberculosis drugs, when present together, interact with each other in a multiple and complex manner.

Antitubercular Agents↗
PubMed1980

Preliminary studies on the validity of in vitro measurement of drug toxicity using HeLa cells. III. Lethal action to man of 43 drugs related to the HeLa cell toxicity of the lethal drug concentrations.

The human lethal plasma concentrations of 46 drugs were divided by their IC50 for HeLa cells in vitro to make up a series of cytotoxic quotients (CQLv). CQLv was then compared with the recorded lethal action to man of 43 of the drugs. While the 7 drugs with the lowest CQLv values produce a non-cytotoxic interference with neuro-transmission, most of the remaining 36 drugs have a known local or systemic cytotoxicity to man. A majority of the 36 drugs induces a non-specific central nervous system (CNS)-depression at lethal dosage, intermingled with function loss from organs outside CNS in proportion to decreasing drug accumulation in CNS cells and increasing CQLv. The remaining drugs which do not penetrate CNS cells and at lethal dosage induce a widespread injury and function loss of tissues outside the CNS, have a CQLv near unity. Non-specific CNS-depression may thus be the primary human reaction to lethal systemic drug cytotoxicity, while widespread drug injury to various tissues outside CNS--conventionally considered to be cytotoxic in origin--may be the obligatory human reaction to drugs that do not penetrate cells well. The present findings indicate a relevance to human toxicity of the HeLa toxicity for most drugs.

Cell Survival↗
PubMed2002

Dual dependence: assessment of dependence upon alcohol and illicit drugs, and the relationship of alcohol dependence among drug misusers to patterns of drinking, illicit drug use and health problems.

AIMS: The study investigates severity of alcohol dependence among drug misusers. Specifically, it investigates the inter-relationship of alcohol and drug dependence and associations with alcohol consumption, drug consumption and substance-related problems. DESIGN, SETTING, PARTICIPANTS: The sample comprised 735 people seeking treatment for drug misuse problems, who were current (last 90 days) drinkers. MEASUREMENTS: Data were collected by structured face-to-face interviews. Dependence upon illicit drugs and upon alcohol was measured by the Severity of Dependence Scale (SDS). FINDINGS: Three groups of drinkers were identified: non-alcohol-dependent drug misusers (63%); low-dependence (19%); and high-dependence (18%). Many drug misusers were drinking excessively and alcohol dependence was related to patterns of alcohol and drug consumption. High-dependence drinkers were more likely to drink extra-strength beer; they were less frequent users of heroin and crack cocaine but more frequent users of benzodiazepines, amphetamines and cocaine powder; they reported more psychological and physical health problems. The SDS was found to have good reliability and validity as a measure of alcohol dependence. SDS scores for alcohol and drug dependence were unrelated. CONCLUSIONS: Alcohol use is an important and under-rated problem in the treatment of drug misusers. A comprehensive assessment of alcohol use among drug misusers should include separate assessments of alcohol consumption, alcohol-related problems and severity of alcohol dependence.

Adult↗