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Because of two hyperthermias, due to metapramine a french antidepressives of the tricyclic family, international literature concerning drug fever induced by psychotropics was reviewed. This study stresses the fact that apart from neuroleptics which are frequently involved in that type of accident, other psychotropics are very rarely responsible of hyperthermia. One hundred and five cases published since 1970 and sufficiently well documented to be analysed according to Dangoumeau's french method of imputation of side effects of drugs, were reviewed. Among these cases, one hundred (95%) corresponded to malignant syndrome of neuroleptics, 89 concerned neuroleptics alone, and 11, neuroleptics associated with other psychotropics. Regarding the different mechanisms which can explain drug fever as described by Lipsky, it seems that concerning psychotropics two types may be retained: Fever due to central dysregulation directly induced by drugs, and mainly, immunoallergic fever, the most frequently seen as described in our two cases.

Many studies have been done to try to define new therapeutic uses for calcium antagonists, in diseases in which calcium plays a role. Positive results have been obtained in the prevention of acute attacks of idiopathic Raynaud's disease and migraine, and in effort-induced asthma. Some activity could be demonstrated in selected groups of patients with pulmonary hypertension, manic-depressive illness, untractable epilepsy, various functional gynecological or digestive disorders, and in drug-induced nephrotoxicity. A possible effect on the prevention of resistance to anti-cancer drugs could be of major interest. Their antiplatelet effect, and their possible effect against atherosclerosis, which remains to be confirmed, their lack of side-effects in asthmatics and of interference with glucose regulation increase their usefulness in patients with hypertension or ischemic heart disease, especially when other diseases are present.

This multicentre, randomized, double-blind study evaluated the effectiveness and safety of cefixime versus amoxicillin. Patients were admitted if they had lower respiratory tract infection with a bacterial pathogen susceptible to both study drugs. Diagnoses included acute respiratory tract infections with no underlying pulmonary pathology (cefixime 21, amoxicillin 27), acute exacerbation of chronic obstructive lung disease (cefixime 32, amoxicillin 42), superinfection of viral bronchitis or lung cancer, and pleuritis (cefixime 10, amoxicillin 6). Patients were treated for at least 10 days with either cefixime 200 mg b.d. or amoxicillin 1 g b.d. A clinical success rate of 80.7 per cent (50/62) in the cefixime group and 82.2 per cent (60/73) in the amoxicillin group was achieved in infections due to susceptible organisms. In acute infections with no underlying pathology, the clinical success rate was 90.5 per cent with cefixime and 81.5 per cent with amoxicillin. Twenty-three cefixime patients and 20 amoxicillin patients were seen 2 to 6 weeks after treatment: there were 2 and 1 clinical recurrences, respectively. All 3 patients were suffering from chronic obstructive lung disease. The bacteriological eradication rate at the end of treatment in assessable patients was 94.7 per cent (17/18) with cefixime and 80 per cent (16/20) with amoxicillin. Six and 11 new organisms appeared, responsible for 2 superinfections under cefixime and 7 under amoxicillin. Treatment was well tolerated by 96.4 per cent of cefixime patients and 90 per cent of amoxicillin patients. This study confirms the value of cefixime as a new oral antibiotic in the treatment of lower respiratory tract infections in adults.

Malignant histiocytosis beginning by a unique pulmonary location is most unusual. The case reported here has seemed worthy because of its strange clinical aspect, the unexpected diagnosis, and because of the way it answered completely and rapidly to the following chemotherapy: Adriamycin 50 mg/m2, Cyclophosphamide 750 mg/m2, Vincristine 2 mg one day every three weeks associated to Prednisone 100 mg/m2 the five first days. A study of literature has allowed us to review all pleuro-pulmonary location initiating malignant histiocytosis and to stress out the errors of diagnosis that can outcome in this case.

Bronchial side effects of drugs are varied and numerous. The most frequent are the hypersensitivity type 1 and 3 reactions of asthma. Asthma is primarily caused by anti-infectious agents but also by protein drugs (and many others). At the present time, attention is being focused on excipients and solvents: cremophore, anti-oxidative sulfites (E 220 to E 227), found in over 700 drugs and responsible for severe side effects. Other bronchospasms are due to direct or indirect potentiation of parasympathetic bronchomotor tonus, chiefly with alpha-agonists, and perhaps with beta-agonists but this remains to be proven. Asthmatic reactions caused by interference in mediator synthesis are another current topic of study; some are well known, such as histamine release and interference in arachidonic acid metabolism (non-steroidal antiinflammatory drugs). Other side effects are the result of local irritation, obstruction or bronchial stenosis. A drug-induced cough could be a consequence of local irritation or of the action of converting enzyme inhibitors on bradykinin catabolism.

Effects of three beta antagonist eye drops are studied in three parallel groups of asthmatic patients. Each ocular topic lowers FEV1 with a maximal effect of -13.4 +/- 2.1% for timolol (n = 15), -17.9 +/- 3.3% for metipranolol (n = 10), and -8.6 +/- 3.0% for carteolol (n = 10). Vital capacity, systolic and diastolic pressure scarcely change, but all three eye drops give a dose dependent sinus bradycardia. Intravenous infusion of isoproterenol (exclusive beta agonist) shows an important inhibition of cardiac receptors by timolol. Doses necessary to increase heart rate of 50% are of 0.242 +/- 0.019 microgram/kg before eye drops are instilled and of 0.647 +/- 0.054 microgram/kg after timolol treatment. This study stresses out the necessity of following recommended doses and respecting carefully classical contra indications of beta blocking agents and specially asthma.

Cough is a well recognised though undesirable side effect during the course of treatment with angiotensin converting enzyme inhibitors (IEC). With the help of two examples we have tried to show that this cough does not have an immunological origin but rather pharmacological. Cough was suppressed by non steroidal anti-inflammatory drugs. Stemming from these observations and from two studies in the literature a patho-physiological mechanism for the cough is proposed in which treatment with IEC leads to a connection with prostaglandins, notably bronchial PGE2.

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.

Five clinical cases of interaction between benzodiazepines on one hand and erythromycin, troleandomycin, josamycin and cimetidine on the other hand have been analyzed. These interactions resulted in severe disorders of behaviour, amnesia (including amnesia-automatism syndrome in one case), disturbances of consciousness and withdrawal syndrome. These disorders were consecutive to inhibition of the hepatic cytochrome P-450 system. Practical means of avoiding this risk consists in limiting such drug combinations, reducing benzodiazepine dosage and, if a combined treatment is necessary, using by preference either benzodiazepines degraded by conjugation instead of oxidation, or macrolides, or anti-H2 compounds with reduced inhibitory effect on microsomes.

Systemic mastocytosis is an uncommon disorder due to multiorgan infiltration by mast cells. The authors report the case of a man whose mastocytosis was revealed in an unusual way by hepatomegaly and portal hypertension of the sinusoidal type. This case was also characterized by the absence of urticaria pigmentosa, the presence of seborrheic warts in which mast cell infiltration was noted and the absence of digestive symptoms. The peculiarities of this case are compared to the published data.

Drug-induced pleural side effects are rare and not usually identified. They may be a fibrous thickening of the pleura or an effusion, generally associated with an interstitial pneumopathy. Sometimes the pleural fluid is clear, sometimes hemorrhagic, and of varied cytological composition. The effusion can be uni- or bilateral. In the majority of cases, the pleural involvement stops when the causative agent is withdrawn. The pathology is usually attributed to a hypersensitivity mechanism when the following drugs have been given: nitrofurantoin, salazopyrine, erythromycin, ampicillin, gold salts, phenytoin, methysergide, ergotamine and bromocriptine. Some pleural lesions resemble lupus (induced by beta-blockers, hydralazine or procainamide). Amiodarone can cause fibroses or effusions via a toxic or hypersensitivity mechanism. In some instances, the mechanism remains unknown (1 case with imipramine, 1 case of fibrosis with perhexiline, 1 case of effusion with ibuprofen, 4 cases of effusion induced by dandrolene).

The authors report the results of a one year study carried out in the Department of Internal Medicine at Laennec Hospital. Out of a total of 1334 hospitalisation, 95 had drug side effects (7.1 p. 100) and 3.5 p. 100 of admissions were directly related to a iatrogenic complication. These complications were more common in women and elderly patients. Sixty-two drugs were implicated: antibiotics (32.6 p. 100), cardiovascular drugs (20 p. 100) including the diuretics (8.4 p. 100), antiinflammatory and antalgic drugs (16.8 p. 100), anticoagulants (8.4 p. 100), neuropsychiatric drugs (7.4 p. 100), oral hypoglycaemic agents (6.3 p. 100)..., 101 side effects were observed: gastro-intestinal (35.6 p. 100) dermato-anaphylactic (19.8 p. 100), cardiovascular (12.9 p. 100), endocrine or metabolic (11.8 p. 100), neuropsychiatric (10.9 p. 100), haematological (5.9 p. 100) and renal (4.2 p. 100). Iatrogenic complications were responsible for the admission to hospital of 47 patients and for 390 days of hospitalisation, costing approximately 380.000 FF.

Systemic effects of two topical B adrenergic blocking agents, carteolol and metipranolol, recently introduced in the treatment of open angle chronic glaucoma, were investigated in two groups of 10 asthmatic patients, according to a controlled trial device. Saline eye drops as placebo, then, 30 mn later beta blocker eye-drops, were instillated at usual dose. Heart rate, systolic and diastolic blood pressure, vital capacity (VC) and expiratory outflow (FEV1), were checked every 15 mn during 90 mn. They did not vary under placebo. After carteolol and metipranolol, heart rate decreased more than 10% in 7 out of 10 patients in each group (extreme individual changes: -16.7 and -25.0%). Bradycardia was always sino atrial. FEV1 was lowered in 3 patients with carteolol and in 6 with metipranolol (extreme individual values: -32.3 and -31.8%). If time is not taken in consideration, the lowest values were -8.6 +/-4.6% with carteolol and -17.9 +/- 3.3% with metipranolol. CV was reduced only in 1 patient under carteolol and 2 patients under metipranolol. Systemic blood pressure remained unchanged. 7 patients complained of ocular pain when metipranolol was instillated. Comparison of both ocular topics shows that metipranolol lowers heart rate and FEV1 more than carteolol, which has a sympathomimetic intrinsic activity. These two drugs have the same clinical efficiency. Our results point out the risks outcoming from their systemic diffusion, and the absolute necessity to comply with the general rules of good use of beta blockers, even with eye drops, mainly the contra-indications and the strict adjustment of individual doses.