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Biomedical subjects

F C Hugues

Publications and source records attributed to F C Hugues.

At least 19 recordsLinked to original sources

[Drug induced orthostatic hypotension].

Therapeutic drugs are the main cause of postural hypotension, notably in elderly people. This syndrome is harmful as it reduces patients' compliance with treatment and is responsible for severe accidents. Drugs which lower cardiac output by acting on heart rate and cardiac muscle contractility, and drugs which decrease blood volume may produce postural hypotension; diuretics are often responsible for hypovolemia and hypokalaemia. The principal mechanisms involved are interferences of drugs with vegetative blood pressure regulation. They include vasomotor centre depressors (morphine-like compounds, antihypertensive agents, neurosedatives, neuroleptics, antiparkinsonians); ganglioplegics; inhibitors of noradrenaline production (methyldopa, disulfiram) or re-uptake (antidepressants); catecholamine depressors (guanethidine); drugs acting on chromaffin granules (monoamine oxidase inhibitors) and those which inhibit post-synaptic receptors (alpha- and beta-blockers). Drugs which act on vascular smooth muscle tone (nitrites, calcium channel antagonists, angiotensin-converting enzyme inhibitors) occasionally cause postural hypotension. To the actions of these drugs must be added endogenous and exogenous factors and notably physiological ageing of the baroceptor reflex; these factors must be taken into account whenever therapeutic drugs are prescribed.

Adolescent

Pharmacokinetics of intravenous bisoprolol in obese and non-obese volunteers.

The pharmacokinetics of a single i.v. dose of dl-bisoprolol 0.16 mg.kg-1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 1351) and a decrease in Vz per kg body weight (2 vs 2.71.kg-1). There was a negative correlation between Vz l.kg-1 and the percentage of ideal body weight (r = -0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.

Adrenergic beta-Antagonists

Dizziness in the elderly and calcium channel antagonists.

Because of the benefit-risk ratio in their favor, calcium channel antagonists are considered to be a safe form of treatment of hypertension in the elderly. However, the outcome of dizziness in some patients over 65 yr old during the first few days of treatment with these drugs has to be considered. Five cases of "malaise" have been mentioned, which occurred during the first few days of treatment. The imputability of the drug in question has been evaluated. Additional factors have been found, ie orthostatic hypotension whatever its mechanism, and association with diuretics, with or without hyponatremia. The above-mentioned cases led to a study in 10 supine elderly women (mean age 85 +/- 3 yr) with normal blood pressure. In this study, systolic and diastolic blood pressure were monitored after a 20-mg oral dose of nicardipine for 3 h. Even in the supine position, a significant fall in blood pressure was observed as early as the 15th min after administration, which could be significant, occasionally reaching 45% of the initial value. Before administering a calcium channel antagonist to an elderly person, orthostatic hypotension has to be investigated. Association with a diuretic results in high risk due to hypovolemia that can enhance the vasodilatory effect of calcium antagonists.

Aged

[Cardiovascular responses to passive and active orthostatism in healthy subjects, in relation to age].

Changes in heart rate induced by inclining an orthostatic table to 30 degrees and 60 degrees and by standing was studied in 200/healthy volunteers of either sex. Study subjects were divided in eight ten-year age groups, from 16 to 97 years. The 56-65 year age group was the youngest group to develop systolic orthostatic hypotension. This response occurred in 4% of subjects aged 56-65 years and became increasingly prevalent from one age group to the next (25%, 36% and 44%). In some patient, the fall in systolic BP reached 70 mmHg. Systolic hypotension occurred in some patients at 30 degrees but in most cases developed only at 60 degrees. No significant difference was found between the falls in SBP seen at 60 degrees and during active standing (90 degrees), indicating that muscular activity does not play a major role in BP regulation. Diastolic hypotension was less common and was mainly seen in patients above 75 (20%) who also had systolic hypotension. Orthostatism was responsible for tachycardia but this response became increasingly less common beyond 55 years of age (60, 60, 52 and 36% in the four age groups above 55). This reflects increasing loss of sensitivity of the baroreflex with advancing age. These date are useful for comparing the age-specific effects of disease states (e.g. diabetes mellius, alcohol abuse) or treatments (psychoactive drugs, antihypertensive agents).

Adolescent

Systemic effects of three beta-blocker eyedrops: comparison in healthy volunteers of beta 1- and beta 2-adrenoreceptor inhibition.

The beta 1- and beta 2-adrenoreceptor blockade by means of the systemic diffusion of three beta-blocker eyedrops--timolol, carteolol, and betaxolol--was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the beta 1- and beta 2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The beta 1-blockade effect was judged on the variation of heart rate, and the beta 2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the beta 1 and beta 2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory.

Adrenergic beta-Antagonists

Comparison of propranolol and sotalol pharmacokinetics in obese subjects.

Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108 mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/- 0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or 2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal half-life (3.9 +/- 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

Adult

[Controlled multicentric study comparing cefixime and amoxicillin in the treatment of lower respiratory tract infections in adults].

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.

Adolescent

Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol.

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.

Adrenergic beta-Antagonists

[Bronchial manifestation of drug-induced complications].

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.

Adrenergic alpha-Antagonists

[The thyroid nodule. A retrospective study of 200 cases].

We analysed 200 cases of thyroid nodules collected in 2 units of the Laennec Hospital. The results of clinical examination, complementary investigations per and post-operative histology and medical follow up were analysed and compared with those in the literature. The malignancy rate was 18%. With the exception of 5 cases, a rigorous medical examination revealed at least one suspicious clinical sign in these patients. Thyroid isotope scan, which was cold in 82% of cases was of no value in distinguishing between benign and malignant nodules. The authors were not in agreement on the policy to be followed when faced with an isolated cold nodule. Fine needle aspiration is the only method which allows diagnosis but it is of low reliability. Ultrasound may be reassuring when it demonstrates fine walled, small diameter cysts only, but this situation is rare. We analysed the limits and pitfalls of these various methods. It is difficult to submit a patient to regular follow up for several years with antagonist treatment, where appropriate, and in addition malignant transformation may not be recognized. With knowledge of the good prognosis of cancers operated on at the microscopic intracapsular stage and the significant number of microscopic carcinomas discovered fortuitously in the course of surgery, it would appear reasonable to at least perform a cervicotomy with extemporaneous histological examination of any cold or isofixing nodule. Lobo-isthmectomy is in practice the solution adopted and its complications are rare and minimal.

Adult

[Drug-induced pleural pathology (excluding antineoplastic chemotherapy)].

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).

Drug-Related Side Effects and Adverse Reactions

[Asthma and beta-blocker eye drops (timolol, metipranolol, carteolol). Inhibition of chronotropic effects of isoprenaline].

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.

Adult

[Adrenergic therapy and vigilance: beta-2 sympathomimetic aerosols in asthma].

It has been established that the use of beta-2 sympathomimetic aerosols is a safe and efficacious treatment of asthma. Unexpected cases of sudden death amongst insufficiently-treated patients or patients who stopped their treatment are not linked with the use of these drugs. To assess the risk of possible "receptor desensitization" it is necessary to notify these accidents to the Committee on Safety of Drugs and to take into consideration the opposite results of further administration and termination of treatment.

Adrenergic beta-Agonists

[Interactions of antitubercular drugs].

Antituberculous drugs are never used alone but are often given concomitantly with drugs prescribed for other diseases. We have therefore reviewed the potential interactions of antituberculous drugs between themselves and with other drugs. Rifampicin being a potent enzyme inducer will decrease the plasma levels of a wide range of drugs. This in turn will decrease the effectiveness of these drugs if they are unmetabolized and active, or increase drug toxicity if the metabolites are toxic. Within the first category are the oral contraceptives, steroids, oral antidiabetics, oral anticoagulants and digitalis. Within the second category is thought to be isoniazid on account of its hepatotoxicity. In contrast, isoniazid (INH) is an enzyme inhibitor. Drugs with hepatic metabolism will tend to accumulate, although this seems clinically relevant only with antiepileptic drugs, diazepam, triazolam and oral anticoagulants (with high INH doses). Many other cases of drug interaction have been described, but they seem to be rare and may not be clinically relevant. INH and rifampicin do not seem to modify each other's metabolism consistently, but it may be wise to check the serum INH levels during coadministration. As said above, rifampicin does increase the hepatotoxicity of INH. INH also inhibits monoamine oxidase and will interact with other MAOI, as well as with fish, cheese or wine with high histamine or tyramine contents. The only interaction found with ethambutol is with diazepam: it increases its clearance and free fraction. Obviously, streptomycin potentiates the ototoxicity of other amino-glycosides, such as capreomycin, kanamycin or viomycin, so that combining them is strictly contra-indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents