Drug interactions of clinical importance with antihyperglycaemic agents: an update.
in Drug Safety : An International Journal of Medical Toxicology & Drug Experience (2005), 28(7), 601-31
Because management of type 2 diabetes mellitus usually involves combined pharmacological therapy to obtain adequate glucose control and treatment of concurrent pathologies (especially dyslipidaemia and ... [more ▼]
Because management of type 2 diabetes mellitus usually involves combined pharmacological therapy to obtain adequate glucose control and treatment of concurrent pathologies (especially dyslipidaemia and arterial hypertension), drug-drug interactions must be carefully considered with antihyperglycaemic drugs. Additive glucose-lowering effects have been extensively reported when combining sulphonylureas (or the new insulin secretagogues, meglitinide derivatives, i.e. nateglinide and repaglinide) with metformin, sulphonylureas (or meglitinide derivatives) with thiazolidinediones (also called glitazones) and the biguanide compound metformin with thiazolidinediones. Interest in combining alpha-glucosidase inhibitors with either sulphonylureas (or meglitinide derivatives), metformin or thiazolidinediones has also been demonstrated. These combinations result in lower glycosylated haemoglobin (HbA(1c)), fasting glucose and postprandial glucose levels than with either monotherapy. Even if modest pharmacokinetic interferences have been reported with some combinations, they do not appear to have important clinical consequences. No significant adverse effects, except a higher risk of hypoglycaemic episodes that may be attributed to better glycaemic control, occur with any combination. Challenging the classical dual therapy with sulphonylurea plus metformin, there is a recent trend to use alternative dual combinations (sulphonylurea plus thiazolidinedione or metformin plus thiazolidinedione). In addition, triple therapy with the addition of a thiazolidinedione to the metformin-sulphonylurea combination has been recently evaluated and allows glucose targets to be reached before insulin therapy is considered. This triple therapy appears to be safe, with no deleterious drug-drug interactions being reported so far.Potential interferences may also occur between glucose-lowering agents and other drugs, and such drug-drug interactions may have important clinical implications. Relevant pharmacological agents are those that are widely coadministered in diabetic patients (e.g. lipid-lowering agents, antihypertensive agents); those that have a narrow efficacy/toxicity ratio (e.g. digoxin, warfarin); or those that are known to induce (rifampicin [rifampin]) or inhibit (fluconazole) the cytochrome P450 (CYP) system. Metformin is currently a key compound in the pharmacological management of type 2 diabetes, used either alone or in combination with other antihyperglycaemics. There are no clinically relevant metabolic interactions with metformin, because this compound is not metabolised and does not inhibit the metabolism of other drugs. In contrast, sulphonylureas, meglitinide derivatives and thiazolidinediones are extensively metabolised in the liver via the CYP system and thus, may be subject to drug-drug metabolic interactions. Many HMG-CoA reductase inhibitors (statins) are also metabolised via the CYP system. Even if modest pharmacokinetic interactions may occur, it is not clear whether drug-drug interactions between oral antihyperglycaemic agents and statins may have clinical consequences regarding both efficacy and safety. In contrast, a marked pharmacokinetic interference has been reported between gemfibrozil and repaglinide and, to a lesser extent, between gemfibrozil and rosiglitazone. This leads to a drastic increase in plasma concentrations of each antihyperglycaemic agent when they are coadministered with the fibric acid derivative, and an increased risk of adverse effects.Some antihypertensive agents may favour hypoglycaemic episodes when co-prescribed with sulphonylureas or meglitinide derivatives, especially ACE inhibitors, but this effect seems to result from a pharmacodynamic drug-drug interaction rather than from a pharmacokinetic drug-drug interaction. No, or only modest, interferences have been described with glucose-lowering agents and other pharmacological compounds such as digoxin or warfarin. The effects of inducers or inhibitors of CYP isoenzymes on the metabolism and pharmacokinetics of the glucose-lowering agents of each pharmacological class has been tested. Significantly increased (with CYP inhibitors) or decreased (with CYP inducers) plasma levels of sulphonylureas, meglitinide derivatives and thiazolidinediones have been reported in healthy volunteers, and these pharmacokinetic changes may lead to enhanced or reduced glucose-lowering action, and thus hypoglycaemia or worsening of metabolic control, respectively. In addition, some case reports have evidenced potential drug-drug interactions with various antihyperglycaemic agents that are usually associated with a higher risk of hypoglycaemia. [less ▲]Detailed reference viewed: 51 (3 ULg)
Drug Interactions with Normal and TEN Epidermal Keratinocytes.
; Delvenne, Philippe ; PIERARD, Gérald
in Current Drug Safety (2012), 7(5), 352-6
Human epidermal keratinocytes (EKs) are metabolically involved in various drug transport mechanisms, as well as in detoxification or activation processes. The overall cell mechanisms of drug ... [more ▼]
Human epidermal keratinocytes (EKs) are metabolically involved in various drug transport mechanisms, as well as in detoxification or activation processes. The overall cell mechanisms of drug metabolization, and more specifically drug processing are reviewed in normal EKs. The overall drug metabolism involves different phases corresponding to the uptake, biotransformation and anti-transport steps. In EKs, both the enzymes and transportassociated proteins are different from those involved in the hepatocyte metabolism. Some cytochrome P450 enzymes and the flavin-containing mono-oxygenases are particularly involved in EKs. Basically, EKs represent key cells likely involved during the initial stage of drug-induced toxic epidermal necrolysis (TEN). Only limited advances have been made so far in this field. Nevertheless, mitigating EKs metabolic disturbances in TEN probably represent a promising specific treatment of the disease. [less ▲]Detailed reference viewed: 11 (3 ULg)
Drug related problems and interventions of pharmacists on prescribed medicines in Belgium
; ; et al
in International Journal of Clinical Pharmacy [=IJCP] (2013, June), 35(3), 497
Aim of project/study (1) To study the frequency and nature of drug related problems (DRP) detected by community pharmacists and internship students when dispensing prescribed medicines. (2) To investigate ... [more ▼]
Aim of project/study (1) To study the frequency and nature of drug related problems (DRP) detected by community pharmacists and internship students when dispensing prescribed medicines. (2) To investigate the nature and frequency of interventions by pharmacists. (3) To study whether there is a difference between DRP detection at the moment of dispensing versus in a quiet setting. [less ▲]Detailed reference viewed: 98 (13 ULg)
Drug resistance among therapy-naive HIV-infected patients studied by sequencing and VERSANT (TM) HIV-1 resistance assays (LiPA) has limited impact on treatment response
; ; et al
in Antiviral therapy (2002), 7(Suppl. 1), 181Detailed reference viewed: 12 (3 ULg)
Drug sensitivity and clinical aspects of Plasmodium falciparum malaria in african children
; ; et al
Conference (1994, October)Detailed reference viewed: 12 (1 ULg)
Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s. Achievements and future developments.
in Drugs (1997), 54(3), 355-68
Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a heterogeneous disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. There are various ... [more ▼]
Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a heterogeneous disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. There are various pharmacological approaches to improving glucose homeostasis, but those currently used in clinical practice either do not succeed in restoring normoglycaemia in most patients or fail after a variable period of time. For glycaemic regulation, 4 classes of drugs are currently available: sulphonylureas, biguanides (metformin), alpha-glucosidase inhibitors (acarbose) and insulin, each of which has a different mode and site of action. These standard pharmacological treatments may be used individually for certain types of patients, or may be combined in a stepwise fashion to provide more ideal glycaemic control for most patients. Adjunct treatments comprise a few pharmacological approaches which may help to improve glycaemic control by correcting some abnormalities frequently associated with NIDDM, such as obesity (serotoninergic anorectic agents) and hyperlipidaemia (benfluorex). There is intensive pharmaceutical research to find new drugs able to stimulate insulin secretion (new sulphonylurea or nonsulphonylurea derivatives, glucagon-like peptide-1), improve insulin action (thiazolidinediones, lipid interfering agents, glucagon antagonists, vanadium compounds) or reduce carbohydrate absorption (miglitol, amylin analogues, glucagon-like peptide-1). Further studies should demonstrate the superiority of these new compounds over the standard antidiabetic agents as well as their optimal mode of administration, alone or in combination with currently available drugs. [less ▲]Detailed reference viewed: 27 (0 ULg)
Drug-delivery implants : Pharmaceutical advantages and current processing technologies
; Jérôme, Christine ;
Scientific conference (2014, February 25)Detailed reference viewed: 21 (4 ULg)
Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide.
in Clinical Pharmacokinetics (2007), 46(2), 93-108
This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for ... [more ▼]
This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for improving insulin secretion of patients with type 2 diabetes mellitus. They are increasingly used either in monotherapy or in combination with other oral antihyperglycaemic agents for the treatment of type 2 diabetes. Compared with sulfonylureas, glinides have been shown to (i) provide a better control of postprandial hyperglycaemia, (ii) overcome some adverse effects, such as hypoglycaemia, and (iii) have a more favourable safety profile, especially in patients with renal failure.The meal-related timing of administration of glinides and the potential influence of food and meal composition on their bioavailability may be important. In addition, some food components (e.g. grapefruit juice) may cause pharmacokinetic interactions. Because glinides are metabolised via cytochrome P450 (CYP) 3A4 isoenzyme, they are indeed exposed to pharmacokinetic interactions. In addition to CYP3A4, repaglinide is metabolised via CYP2C8, while nateglinide metabolism also involves CYP2C9. Furthermore, both compounds and their metabolites may undergo specialised transport/uptake in the intestine, another source of pharmacokinetic interactions. Clinically relevant drug-drug interactions are those that occur when glinides are administered together with other glucose-lowering agents or compounds widely coadministered to diabetic patients (e.g. lipid-lowering agents), with drugs that are known to induce (risk of lower glinide plasma levels and thus of deterioration of glucose control) or inhibit (risk of higher glinide plasma levels leading to hypoglycaemia) CYP isoenzymes concerned in their metabolism, or with drugs that have a narrow efficacy : toxicity ratio.Pharmacokinetic interactions reported in the literature appear to be more frequent and more important with repaglinide than with nateglinide. Rifampicin (rifampin) reduced repaglinide area under the plasma concentration-time curve (AUC) by 32-85% while it reduced nateglinide AUC by almost 25%. Reported increases in AUCs with coadministration of drugs inhibiting CYP isoenzymes never exceeded 80% for repaglinide (except with ciclosporin and with gemfibrozil) and 50% for nateglinide. Ciclosporin more than doubled repaglinide AUC (+144%), a finding that should raise caution when using these two drugs in combination. The most impressive pharmacokinetic interaction was reported with combined administration of gemfibrozil (a strong CYP2C8 inhibitor) and repaglinide (8-fold increase in repaglinide AUC). Although no studies have been performed in patients with type 2 diabetes, the latter combination should be avoided in clinical practice. [less ▲]Detailed reference viewed: 105 (1 ULg)
Drug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
in Clinical pharmacokinetics (2014)
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel ... [more ▼]
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (C max) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment. [less ▲]Detailed reference viewed: 20 (0 ULg)
Drug-eluting stents: a study of international practice.
; ; et al
in American heart journal (2009), 158(4), 576-84
OBJECTIVE: We aimed to analyze trends in drug-eluting stents (DES) use in four international health care and regulatory settings. BACKGROUND: Accounts suggest a differential approach to DES ... [more ▼]
OBJECTIVE: We aimed to analyze trends in drug-eluting stents (DES) use in four international health care and regulatory settings. BACKGROUND: Accounts suggest a differential approach to DES internationally and recent reductions in use following reports of late stent thrombosis. Current studies of clinical practice are limited in their scope. METHODS: Data were pooled from angioplasty registries in Alberta (Canada), Belgium, Mayo Clinic (Rochester, MN), and Scotland (UK) that have routinely recorded consecutive patients treated since 2003. Trend analysis was performed to examine variations in DES use over time and by clinical subgroup. RESULTS: A total of 178,504 lesions treated between January 2003 and September 2007 were included. In the Mayo Clinic Registry, rapid adoption to a peak of 91% DES use for all lesions by late 2004 was observed. In contrast, Alberta and Scotland showed delayed adoption with lower peak DES use, respectively, 56% and 58% of lesions by early 2006. Adoption of DES in Belgium was more gradual and peak use of 35% lower than other registries. Reductions in DES use were seen in all data sets during 2006, although this varied in absolute and relative terms and by clinical subgroup. CONCLUSION: Adoption and use of DES showed wide variation in four countries. The determinants of use are complex, and it is likely that nonclinical factors predominate. Recent reductions in use may be as a consequence of publicity and concerns regarding late stent thrombosis. The optimum application of DES in clinical practice is unclear and is reflected in the degree of international variation demonstrated. [less ▲]Detailed reference viewed: 4 (0 ULg)
Drug-eluting stents: meta-analysis in diabetic patients.
Scheen, André ; Warzee, Fabian ; Legrand, Victor
in European heart journal (2004), 25(23), 2167-82168-9Detailed reference viewed: 14 (3 ULg)
Drug-induced changes in cortical inhibition in medication overuse headache.
; ; et al
in Cephalalgia : An International Journal of Headache (2011), 31(12), 1282-90
BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy ... [more ▼]
BACKGROUND: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. SUBJECTS AND METHODS: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. RESULTS: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 +/- 14.2 vs. 108.1 +/- 30.1 ms), but similar to that reported in migraineurs (59.9 +/- 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 +/- 46.4 and 103.8 +/- 47.2 ms). CONCLUSIONS: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission. [less ▲]Detailed reference viewed: 10 (0 ULg)
Drug-induced destructive cholangitis and total ductopenia in a young dog.
; ; et al
in Proceedings of the 13th Annual Congress of the ECVIM-CA (2003)Detailed reference viewed: 92 (2 ULg)
Drug-induced toxic epidermal necrolysis and pancytopenia: a puzzling association.
Paquet, Philippe ; ; et al
in International Journal of Molecular Medicine (2005), 16(1), 29-33
The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also ... [more ▼]
The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also suffered from prolonged severe methotrexate-induced pancytopenia. The objective of the study was to explore the nature of the cutaneous inflammatory infiltrate and the density in dermal dendrocytes (DD). Immunohistochemistry was used to identify activated T lymphocytes (CD45R0), monocyte-macrophages (Mac 387, CD68), DD (Factor XIIIa), and Langerhans cells (CD1a). The proliferation marker (Ki67) and the antibody to Fas receptor (CD95R) were also used to assess the distribution of the germinative pool of keratinocytes and the FAS-related apoptotic process, respectively. Numerous Factor XIIIa+ DD were present in the papillary dermis with only sparce perivascular CD45RO+ T lymphocytes and scattered CD68+ or Mac 387+ macrophages. Double immunostainings revealed that a minority of Factor XIIIa+ DD co-expressed the CD68 glycoprotein (a marker of phagocytic activity). No cells co-expressed factor XIIIa and Mac 387 immunoreactivities. CD45RO+ T lymphocytes, CD68+ and Mac 387+ macrophages were absent in the epidermis. The expression of CD95R was present although restricted to the basal keratinocytes, while the L1-protein (Mac 387+) was diffusely present in the epidermis. Langerhans cells (CD1a+) were sparce, but normal in distribution. The presence of a great number of Factor XIIIa+ DD without any possible recent recruitment from bone marrow suggests that these cells differentiated from resident cells of the skin. Indeed, there was no co-expression of Factor XIIIa and L1-protein, thus showing the absence of recruitment from monocytes. The simultaneous over-expression of Factor XIIIa and CD68 in some DD indicates some phagocytic activity. In view of the absence of inflammatory cells in the epidermis, keratinocytes appeared responsible for their own destruction through CD95-mediated and/or calcium-dependent apoptotic pathways. This finding entails that TEN treatments should target the keratinocyte metabolism rather than the circulating inflammatory cells which presumably play a limited role, if any, in the epidermal destructive process. [less ▲]Detailed reference viewed: 32 (0 ULg)
Drug-induced valvular heart disease.
; ; et al
in Heart (British Cardiac Society) (2013), 99(1), 7-12
Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs ... [more ▼]
Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate management. [less ▲]Detailed reference viewed: 23 (4 ULg)
. Drug-Induced variations of the microviscosity, shape and size of lipid bilayers: interaction of cholesterol and methyl-b-cyclodextrins with DMPC and DPPC liposomes: a SANS study
Grammenos, Angeliki ; Gaspard, Jean-Pierre ; Hoebeke, Maryse et al
Poster (2006, November)Detailed reference viewed: 16 (3 ULg)
Drugs and "Integrated"Policy. Between Intention and Execution
Lemaître, André ; Fincoeur, Bertrand
in Cahiers de la Sécurité (2009)Detailed reference viewed: 18 (4 ULg)
DRUPSSuC : Design and Renovation of Urban Public Spaces for Sustainable Cities, Final report Phase 1
; ; et al
Report (2009)Detailed reference viewed: 73 (7 ULg)