Geneviève Durrieu

Parkinson's disease and weight loss: A study with anthropometric and nutritional assessment

In order to investigate a putative weight loss in patients with Parkinsons disease, an anthropometric and biochemical study was undertaken. We compared body weight and indexes of fat [body mass index (BMI), tricipital skinfold] and lean [midarm muscle area (MMA), calf circumference] mass in men and women suffering from idiopathic Parkinsons disease with normal controls. We found that women suffering from Parkinsons disease exhibited a significant weight loss (−8.5%) and decreased calf circumference when compared with controls. A decrease (−4.3%) in total body weight was also found in men with Parkinsons disease but the difference did not reach the level of significance. Protein biochemical markers of nutritional status (albumin, prealbumin, retinol binding protein, transferrin) were normal in Parkinsons disease patients. The present study demonstrates the occurrence of weight loss in a large population of patients with Parkinsons disease. The putative mechanisms involved in the weight loss are discussed.

Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database

Nefopam is widely used for the relief of moderate acute pain. Its safety profile remains to be specified. The objective of the study was to review adverse reactions to nefopam spontaneously reported to the French Pharmacovigilance system. All cases of adverse drug reactions (ADRs) associated with nefopam, registered in the French Pharmacovigilance database from January 1, 1995 to December 31, 2004, were reviewed. For each reported ADR, information about patient (age, gender, medical history), drug exposure (suspected and concomitantly used drugs), characteristics of ADRs (imputability score, time of onset, seriousness, outcome) were collected. A total of 114 ADRs with an imputability rated from ‘plausible’ (I2) to ‘likely’ (I3) and ‘very likely’ (I4) was analysed. The most frequent ADRs included ‘expected’ ADRs such as sweating, nausea, tachycardia, malaise or vomiting; 61 ADRs were ‘unexpected. No overdose was reported; 26 ADRs (23%) were considered as ‘serious’. Most of them were ‘unexpected’, including neuropsychiatric (hallucinations, convulsions) or cutaneous (pruritus, erythema, urticaria) ADRs. Six cases of anaphylactic ADRs (two angioedema and four anaphylactic shocks) were reported, all occurring shortly after use of nefopam during the post‐operative period. Physicians should be aware of the possible occurrence of some serious ADRs when using nefopam such as convulsions and anaphylactic shocks, especially when the drug is used in special medical conditions, like post‐operative periods.

Drug interactions between antihypertensive drugs and non‐steroidal anti‐inflammatory agents: a descriptive study using the French Pharmacovigilance database

Drug–drug interactions (DDIs) between antihypertensive drugs and non‐steroidal anti‐inflammatory drugs (NSAIDs) can lead to adverse drug reactions (ADRs). Guidelines are available to help prescribers deal with these drug associations, but their implementation is not well evaluated. The aims of this study were to assess the prevalence of NSAIDs exposure in patients treated with antihypertensive drugs, using the French Pharmacovigilance database, and explore the ADRs related to DDIs between antihypertensive drugs and NSAIDs. Over the 11, 442 notifications of ADRs recorded in this database in patients treated with oral antihypertensive drugs between 2008 and 2010, 517 (4.5 and 95% CI: 4.1–4.9) also included exposure to NSAIDs. These subjects were more frequently women, took more drugs in general, and were younger and less frequently treated with antiplatelet drugs. In 24.2% of them (125 patients), a DDI between NSAIDs and antihypertensive drugs was potentially the cause of the reported ADR. Acute renal failure caused by DDIs between NSAIDs and angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or diuretics was the most frequently reported ADR (20.7%). Finally, in the French Pharmacovigilance database, around one‐fourth of associations NSAIDs + antihypertensive drugs are associated with a ‘serious’ ADR (mainly acute renal failure), suggesting that this well‐known DDI is not enough taken into account by prescribers.

Life-threatening drug-associated hyperkalemia: a retrospective study from laboratory signals

Life‐threatening hyperkalemia may be induced by drugs and preventable in at‐risk patients. This study was designed to describe cases of ‘serious’ drug‐associated hyperkalemia.

Relationship Between Arterial Blood Pressure Disturbances and Alpha Adrenoceptor Density

To investigate the influence of blood pressure disturbances on human platelet alpha 2-adrenoceptor density, we studied 7 normotensive Parkinsonians with orthostatic hypotension and 23 mild essential hypertensive patients. Plasma catecholamine levels were measured by HPLC and alpha 2-adrenoceptor number and affinity determined by [3H]-yohimbine binding. Alpha-adrenergic reactivity was investigated by blood pressure response to noradrenaline infusion in Parkinsonians and by adrenaline-induced platelet aggregation in hypertensive patients. In Parkinsonians with orthostatic hypotension, in comparison with Parkinsonians without orthostatic hypotension and normotensive control subjects age and sex matched, noradrenaline plasma levels were significantly lower (62 +/- 11, 195 +/- 14 and 219 +/- 13 pg. ml-1 respectively, p < 0.05), platelet alpha 2-adrenoceptor number was significantly higher (313 +/- 52, 168 +/- 9 and 174 +/- 4 fmol.mg-1 protein respectively, p < 0.05) and the noradrenaline dose required for a 25 mm Hg increase of systolic blood pressure significantly lower (0.19 +/- 0.03, 0.86 +/- 0.11 and 0.68 +/- 0.10 microgram.Kg-1 respectively, p < 0.05). In hypertensive patients, in comparison with normotensive control subjects age and sex matched, plasma noradrenaline levels remained unchanged (306 +/- 68 vs 246 +/- 28 pg.ml-1) whereas both platelet alpha 2-adrenoceptor number (137 +/- 15 vs 177 +/- 15 fmol.mg-1 protein, p < 0.05) and velocity of adrenaline-induced platelet aggregation were significantly decreased. These results indicate that platelet alpha 2-adrenoceptor density is related to blood pressure values. In Parkinsonians with orthostatic hypotension, the up-regulation of alpha 2-adrenoceptors was induced by the decrease of endogenous catecholamines. In contrast, in essential hypertension a down-regulation of alpha 2-adrenoceptors was observed in spite of no significant increase of catecholamine levels. These results suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptor regulatory mechanisms.

Pharmacovigilance, risks and adverse effects of self-medication.

Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, seriousness and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

Adverse drug reactions to self‐medication: a study in a pharmacovigilance database

Although self‐medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self‐medication recorded in the Midi‐Pyrénées PharmacoVigilance between 2008 and 2014. Self‐medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three‐forth of the ADRs were ‘serious’. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy–homeopathy accounted for 9.1% of drugs.

More on the "Triple Whammy": antihypertensive drugs, non-steroidal anti-inflammatory agents and acute kidney injury - a case/non-case study in the French pharmacovigilance database.

Abstract It has been suggested that the risk of acute kidney injury (AKI) increases with the number of drugs associated between non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEis) [or angiotensin receptor blockers (ARBs)] and diuretics. We aimed to investigate whether the number of drugs associated between NSAIDs, ACEis, ARBs and diuretics was associated to disproportionate reporting of AKI in the French Pharmacovigilance Database. In reports of Adverse Drug Reactions (ADRs) recorded between 01 January 2008 and 31 December 2010, we selected patients whose medications included at least one oral antihypertensive drug. We used a case/non-case methodology. Cases were AKI and non-cases were all the remaining reports. Among the 11,442 ADR reports in patients under antihypertensive drug recorded in the French Pharmacovigilance Database, 837 ADRs were AKI (7.3%, 95% CI 6.8–7.8). AKI and the number of drugs associated were disproportionately reported (one drug alone: adjusted ROR 2.19, 95% CI: 1.65–2.89, two drugs: adjusted ROR 5.27, 95% CI: 4.00–6.94, three and more: adjusted ROR 16.46, 95% CI: 11.38–23.80). There was no significant association between NSAIDs’ half-lives and reporting of AKI (adjusted RORu2009=u20090.54, 95% CI: 0.25–1.15). Given the widespread use of these hazardous drugs in general population, caution is needed when they are associated.

Neuropathies médicamenteuses : analyse de la Banque française de pharmacovigilance de 1995 à 2005

INTRODUCTIONnDrug-induced neuropathies are mainly sensory and subacute. The pathophysiological mechanisms associated with them are not clearly established and few pharmacoepidemiologic studies are available.nnnMETHODnThis study investigated spontaneous reports of peripheral neuropathies reported to the French Adverse Drug Reaction (pharmacovigilance) database over a ten-year period.nnnRESULTSnBetween January 1995 and April 2005, 1110 cases were reported, predominantly among men (60%). Patients mean age was 53.6 years. Most of these reports concerned sensory neuropathies, and 538 (48%) cases were considered serious. Neuropathies related to dermatologic drugs (mainly retinoids) were serious in 85.7% of cases. Reactions were tentatively attributed to the following pharmacological classes, in decreasing order: antiviral and antibacterial (43.6%), antineoplastic and immunosuppressant (15.9%), cardiovascular (15.9%), central nervous system (7.9%) and gastrointestinal and metabolism (4.8%) agents. Specific drugs suspected of causing neuropathies were stavudine (198 cases), didanosine (134), lamivudine (124), thalidomide (57), ritonavir (55), zalcitabine (53) and amiodarone (47). This study allowed us to consider whether 2 other drugs (allopurinol and flecainide acetate) might be related to the occurrence of neuropathies.nnnDISCUSSIONnThis work points out the usefulness of spontaneous reports of adverse drug reactions to regional adverse drug reaction reporting centers to help determine the relative frequency of suspected reactions to different drugs and to help detect drugs not previously known to induce these reactions.

Can drugs induce or aggravate sleep apneas? A case-noncase study in VigiBase® , the WHO pharmacovigilance database

The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase®, the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case–noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37‐year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were ‘serious’ in around 82% of cases. The case–noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS.