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At least 181 records · Page 10Linked to original sources
PubMed2006

Unexpected link between iron and drug resistance of Candida spp.: iron depletion enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells.

Inthis study, we show that iron depletion in Candida albicans with bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its sensitivity to several drugs, including the most common antifungal, fluconazole (FLC). Several other species of Candida also displayed increased sensitivity to FLC because of iron restriction. Iron uptake mutations, namely, Deltaftr1 and Deltaftr2, as well as the copper transporter mutation Deltaccc2, which affects high-affinity iron uptake in Candida, produced increased sensitivity to FLC compared to that of the wild type. The effect of iron depletion on drug sensitivity appeared to be independent of the efflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by 15 to 30%. Subsequently, fluorescence polarization measurements also revealed that iron-restricted Candida cells displayed a 29 to 40% increase in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot assays revealed that the ERG11 gene was considerably down regulated in iron-deprived cells, which might account for the lowered ergosterol content. Our results show a close relationship between cellular iron and drug susceptibilities of C. albicans. Considering that multidrug resistance is a manifestation of multifactorial phenomena, the influence of cellular iron on the drug susceptibilities of Candida suggests iron as yet another novel determinant of multidrug resistance.

Antifungal Agents↗
PubMed1979

Use of computer drug-drug interaction program for detection of adverse drug reactions and related therapeutic problems.

Pharmacies currently using computers to detect drug-drug interactions may not be fully utilizing the computers' programs. Potential drug-disease interactions and some potential adverse drug reactions not traditionally defined as interactions can be detected by extending the basic concept of cross-referencing. For example, certain clinically important ADRs are readily detected by cross-referencing drugs which are often used to treat the results of specific ADRs with certain causative agents. The potential therapeutic implications of such a system when restricted to clinically significant ADRs can be readily appreciated, especially in situations where the pharmacist's time in patient-care areas is limited. This concept is currently being practiced at Bayfront Medical Center, and has added a new dimension to the clinical services provided by the pharmacy. It seems likely that detection of therapeutic situations in this manner may be appropriate in other hospital settings.

Drug Interactions↗
PubMed2002

Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system.

Liposome-encapsulated drugs often exhibit reduced toxicity and have also been shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs in liposomes has often resulted in an improved overall therapeutic efficacy. The results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for therapy of intracellular M. avium infection show enhanced cellular delivery of liposome-encapsulated antibiotics and suggest that efficiency of intracellular targeting is sufficient to mediate enhanced antimycobacterial effects. The antitubercular drugs encapsulated in lung specific stealth liposomes have enhanced efficacies against tuberculosis infection in mice. These results from stealth liposome study indicate that antitubercular drugs encapsulated in liposome may provide therapeutic advantages over the existing chemotherapeutic regimen for tuberculosis. Liposomes with encapsulated amikacin are able to protect collagen almost completely from adherence of bacterial cells of all strains examined and prevent from invading of bacteria.

Animals↗
PubMed2000

New drug applications; drug master files. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is revising its regulation governing drug master files (DMF's). FDA is removing the provision for submitting Type I DMF's and will no longer permit information submitted in a Type I DMF to be incorporated by reference in investigational new drug applications (IND's), new drug applications (NDA's), abbreviated new drug applications (ANDA's), or amendments or supplements to any of these. This rule is intended to eliminate submissions of information that are not necessary either to conduct inspections of manufacturing facilities or to review the chemistry, manufacturing, and controls sections of IND's, NDA's, and abbreviated applications.

Documentation↗
PubMed2000

Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; amendment of final monograph for OTC antitussive drug products. Food and Drug Administration, HHS. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph for over-the-counter (OTC) antitussive drug products (products that relieve cough). Use of topical/inhalant products containing camphor or menthol near a flame, in hot water, or in a microwave oven may cause the products to splatter and cause serious burns to the user. As part of its ongoing review of OTC drug products, FDA is adding warnings and directions to inform consumers about these improper uses and is amending its final regulations for OTC drug labeling requirements to add this new flammability warning for antitussive drug products containing camphor or menthol.

Anti-Asthmatic Agents↗
PubMed1985

On the non-specific antiinflammatory effects of other-than-antirheumatic drugs. Psychotropic drugs, inflammation and antiinflammatory drugs.

The interference of non-antiinflammatory drugs with inflammation and with the effects of antiinflammatory/antirheumatic drugs (AIDs) is exemplified by various psychotropic drugs (PTDs). The antiinflammatory action was evaluated in 3 ways: (i) drug effects on bentonite raw-paw oedema after a prophylactic and a therapeutic dose in the same rat, (ii) effect on bentonite oedema of single and repeated administrations (oedema induction in the contralateral paw 7 days later, drug administration continued in the interim), and (iii) effects on traumatic rat-ear oedema of single and repeated pretreatment. Most of the PTDs tested (neuroleptics, anxiolytics, psychostimulants, etc.) suppressed significantly the acute oedema, and some of them (caffeine, nomifensine, lisuride, etc.) also suppressed the fully developed oedema. Many PTDs, when given repeatedly, lost their effects or even aggravated the later phase of inflammation. PTDs can interfere also with the antiinflammatory effects of AIDs, since caffeine and guaifenesin, but not nomifensine, increased the antiinflammatory effects of aspirin and paracetamol, although neither caffeine nor nomifensine interfered with the effect of Auranofin. Therefore in clinical practice the interference of PTDs must be taken account: a PTD taken by the patient can mask signs of acute inflammation (including posttraumatic and postsurgical states). Moreover, the antiinflammatory potential of various analgesic/antipyretic combinations containing a PTD should be considered in view of this interference, since this can sometimes be exploited therapeutically.

Animals↗
PubMed1997

Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions: evaluation of a paired approach for psychotropic medication.

The present study investigated the potential of therapeutic drug monitoring data to document pharmacokinetic drug interactions with psychotropic medication, both in terms of methodology and applicability. It focused on 105 patients exposed to one of five agents known for their capacity to induce (phenytoine, phenobarbital, and carbamazepine) or to inhibit (thioridazine and levomepromazine) the metabolism of psychotropic drugs. These patients were matched by gender, age, and monitored psychotropic medication to 105 patients randomly selected from a pool of subjects nonexposed to target comedication. Such a paired approach was shown to be effective in reducing variability for a majority of substances. Power analysis suggested that eight to 10 pairs of exposed and nonexposed patients would effectively allow the detection of twofold effects of interacting substances. In keeping with the literature, analysis of the ratios of dose-normalized exposed to nonexposed concentrations indicated that phenothiazine comedication led to significantly higher concentrations of desmethylated metabolites but not parent compounds, when clomipramine, imipramine, or amitriptyline were administered. A similar, as yet undocumented interaction was observed for the tetracyclic antidepressant mianserine. In contrast, the present study revealed that maprotiline concentrations were increased, but its metabolite was largely unaffected by phenothiazine comedication. Increased concentrations were also observed for moclobemide, but not citalopram or its metabolite. In addition to its long recognized capacity to decrease haloperidol concentrations, carbamazepine was shown to induce the metabolism of clopenthixol and possibly flupenthixol. The consistency of such a picture substantiates the need to consider therapeutic drug monitoring databases as cost-effective and reliable tools for postmarketing surveillance.

Adolescent↗
PubMed2000

Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date; reopening of administrative record. Food and Drug Administration, HHS. Final rule; delay of effective date; reopening of administrative record.

The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.

Drug Industry↗
PubMed2002

Abused drugs modulate RGS4 mRNA levels in rat brain: comparison between acute drug treatment and a drug challenge after chronic treatment.

While different classes of abused drugs interact with distinct signaling substrates, it appears that all utilize receptors in the mesolimbic dopamine system to mediate their reinforcing effects. The regulator of G-protein signaling (RGS) proteins modulate G-protein coupled receptor (GPCR) signaling by increasing the rate of GTP hydrolysis of G proteins. This study was undertaken to determine whether morphine, cocaine, or amphetamine would modulate RGS4 mRNA levels in relevant brain regions. Acute administration of morphine and cocaine decreased levels of RGS4 mRNA in the reticulotegmental pontine nucleus (RtTg) and locus coeruleus (LC). Increases in RGS 4 mRNA levels were observed in the nucleus accumbens (NAc) and dorsal central gray (CGD). Acute drug challenge after chronic drug administration increased RGS4 mRNA in the CGD and decreased RGS4 levels in the red nucleus and RtTg. Interestingly, the LC exhibited biphasic modulation, with decreased RGS4 mRNA levels after acute administration and increased levels after chronic administration. These findings indicate that RGS4 mRNA levels are modulated in a similar manner by different drugs of abuse and imply that a common substrate could mediate some effects of abused drugs.

Animals↗