[Evaluation of ten years of pharmacovigilance of antihypertensive drugs in the Toulouse University Regional Hospital Center (1981-1990)]. / Bilan de dix ans de pharmacovigilance des antihypertenseurs au Centre Hospitalier Régional Universitaire de Toulouse (1981-1990).

The eighties were characterized by the introduction of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) in the treatment of arterial hypertension. The present study investigates the side effects of antihypertensive drugs in the Toulouse University Hospital (France) between 1981 and 1990. Most of the side effects involved ACEI (45%), CCB (22%) and diuretics (18%). Central antihypertensive agents and beta-blocking drugs were involved in 8 and 9% of side effects respectively. During these 10 years, 197 side effects were reported in our hospital (3300 beds). Some of them were found more frequently: renal insufficiency (15%) or cough (9%) with ACEI, constipation (3%), gingivitis (1%) or lower limb oedema (4.5%) with CCB, hemolytic or autoimmune anemia (2.5%) and confusional state (1.5%) with central antihypertensive agents, nightmares (1.5%) with propranolol. The most frequently side effects were dermatological (20%), hydroelectrolytic (10%) and neuropsychiatric (9.6%) disturbances. In spite of the methodological problems of this kind of study (retrospective evaluation, under-notification of the side effects and different scores of imputability), these data indicate the most frequently observed side effects of antihypertensive agents during the eighties. It allows to estimate an approximate frequency of these side effects: among the antihypertensive drugs, CCB and diuretics seems the less frequently involved in the occurrence of reported side effects.

[Multicenter prospective study of cardiac accidents during treatments with 5-FU]. / Etude prospective multicentrique des accidents cardiaques survenus au cours de traitements comportant du 5-FU.

In a prospective, multicenter study, we evaluated the incidence of adverse cardiac effects in 1097 patients receiving 5-FU as a short i.v. perfusion or as a continuous perfusion over 3 to 5 days. There were 29 cardiac events (incidence 1.6%; 4.5% in patients with a history of cardiovascular disease, 1.1% in the remainder). Adverse effects were more frequent in the patients with advanced WHO (WHO = OMS) stage (2 or 3) primary tumors of the upper respiratory or digestive tract, or of the gastrointestinal tract, when 5-FU was given as a continuous perfusion. They also appeared to be more frequent in patients with a history of cardiovascular disease, and mainly occurred during the second or third day of the first course of treatment. Retreatment of eight patients with 5-FU led to the recurrence of symptoms in five. The outcome of these adverse cardiac effects was generally favorable, but 11.5% of the patients died.

[Evaluation of the pharmacovigilance follow-up of zidovudine]. / Bilan d'un suivi de pharmacovigilance de la zidovudine.

A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease.

[Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases]. / Cardiotoxicité du 5-fluorouracile perfusion intraveineuse continue: étude clinique, prévention, physiopathologie. A propos d'une série de 13 cas.

5-Fluorouracil (5FU) cardiotoxicity is thought to be an infrequent toxic effect, usually related to coronary vasospasm. Among 198 patients (pts) receiving 5FU as a continuous infusion (CI) over 96 or 120 h, at a daily dose of 1,000 mg/m2, 13 new cases of 5FU--cardiotoxicity are reported. In all cases but 1, cardiovascular symptoms occurred at the first 5FU-CI course, with mean time of onset of 3 d. Chest pain was the prominent inaugural symptom with angor pectoris (6 pts) and pericarditis (3 pts). Five pts developed cardiogenic shock, which was irreversible in 3 cases. The severity of such an evolution requires prompt 5FU discontinuation, if symptoms occur, and careful hemodynamic supervision during 5FU therapy. One patient experienced typical myocardial infarction, another one epicardo myocardiopathic process with adiastolia. Disorders of repolarisation on electrocardiographic tracing were the prominent abnormalities, associated with a significant increase of QT segment in 3 cases. Re-introduction of 5FU-CI resulted in chest pain recurrence in 2 out of 4 pts, despite calcium antagonist "prevention". In our retrospective study, the incidence of 5FU-CI cardiotoxicity is 6.5%, which is consistent with recent reports (10%). Whether 5FU-induced cardiotoxicity mechanism is related to vasospastic or direct effect remains unclear. However, our series suggests a 5FU-induced post ischaemic myocardial dysfunction as described in the "stunned myocardium" syndrome.

[An intensive survey of drug surveillance in a medical admissions department]. / Enquête intensive de pharmacovigilance dans un service d'admission médicale.

An intensive survey of pharmacovigilance was carried out in a medical admission department over a 4-month period. Out of 2,017 admissions to hospital, 23 (1,1 p. 100) were motivated by adverse reactions to drugs. Questioning brought out allergy and multiple drug therapy as important factors. Lesions of the skin and mucosae predominated, notably after treatment with antibacterial and non-steroidal anti-inflammatory agents. The categories of drugs involved were, in decreasing order of frequency: cardiovascular (6/23), anti-bacterial (5/23), neuropsychiatric (4/23) and non-steroidal anti-inflammatory drugs (4/23). The fact that the patients had taken several products rendered evaluation difficult. Using imputability scales made it possible to reduce the cause-effect relationship in 26 p. 100 of the cases.