Search PubMed⌕ Search

Biomedical subjects

C Advenier

Publications and source records attributed to C Advenier.

At least 199 records · Page 11Linked to original sources
PubMed1984

Bronchopulmonary effects of phenylephrine and methoxamine in the guinea-pig. Interaction with bronchoconstrictor drugs.

The bronchopulmonary effects of phenylephrine (Phe) and methoxamine (Met) were investigated in vitro on isolated guinea-pig tracheas and lung strips and in vivo on pulmonary airway resistance (Raw) in conscious guinea-pigs. Phe, but not Met, relaxed the isolated trachea precontracted with acetylcholine (ACh); this effect was inhibited by propranolol and ascribed to beta-adrenergic stimulation. In the presence of propranolol, both Phe and Met contracted the isolated trachea (-log EC50 were 3.80 +/- 0.37 and 3.04 +/- 0.25 respectively (n = 5] and this effect was competitively antagonized by phentolamine. Phe and Met contracted the isolated lung strips more strongly than the trachea (-log EC50 were 5.14 +/- 0.23 and 4.30 +/- 0.14 respectively (n = 5]. In contrast with the latter, the maximum response was equivalent to that induced by ACh; this effect was also antagonized by phentolamine. In the conscious guinea-pig, Phe (100 and 300 micrograms/kg) and Met (1 and 3 mg/kg) had no effect on Raw but significantly reduced the bronchoconstriction induced by ACh (25 micrograms/kg), histamine (20 micrograms/kg) and serotonin (15 micrograms/kg); this protective effect was unmodified by propranolol (2 mg/kg), yohimbine (1 mg/kg) or piperoxan (0.3 mg/kg) but was significantly inhibited by prazosin (30 micrograms/kg) or AR- C239 (50 micrograms/kg). These results suggest that alpha-adrenergic vasoconstriction with subsequent shrinkage of the bronchial mucosa is responsible for the protective effect of Phe and Met against ACh-induced bronchoconstriction. In isolated lung strips, vasoconstriction would increase tension.

Acetylcholine↗
PubMed1984

[Cromoglycic acid (disodium cromoglycate) and inhibitors of mast cell degranulation].

Cromoglycic acid (disodium cromoglycate) is a diacromone derived from khelline whose chief action in asthma is preventive, through inhibition of mastocyte degranulation. Since its digestive absorption is poor, it is given locally as a pulverulent aerosol. Cromoglycic acid is also used successfully in certain forms of ocular and nasal allergy. An oral preparation of cromoglycic acid is beginning to be used in food allergy and certain rectocolites. Trials are ongoing with several other substances, which have comparable properties and are active orally.

Animals↗
PubMed1984

[Bronchodilators].

Bronchodilating drugs can be divided into three main groups: beta-adrenergic stimulants including specific beta-2 receptor agonists (salbutamol, terbutaline, fenoterol) which are the agents of this group used in everyday practice, theophylline and its derivatives, and atropine-like drugs (ipratropium bromide). Bronchodilators act chiefly upon the spasm observed at the bronchial level in reversible obstructive phenomena (mainly asthma), their effect upon inflammation and hypersecretion being slight or controversial. Beta-stimulants have a relatively specific mode of action at the bronchial level in the setting of use in pneumology; they exhibit cardiac effects only at high doses and when used by oral or parenteral routes. Relative to isoprenaline, they also have the advantage of being active orally and over a longer period of time. They are given in maintenance treatment of asthma, by parenteral or oral routes or as aerosols. Main side effects of adrenergic beta-stimulants are tremor with oral administration, and tachycardia with very high doses by parenteral or oral routes; when given as aerosols these agents may fail to control severe attacks. The bronchodilating properties of theophylline have been known for a long time; late advances concerning this drug result from better knowledge of its pharmacokinetics. Recent studies have discriminated between serum levels correlated with therapeutic effectiveness and those accompanied with mild or severe side effects; in addition, it has been clearly shown that the half life of this alkaloid varies from one person to another and with various physiopathologic (age, dietary habits, liver failure, heart failure...) or pharmacologic (drug interactions with enzyme inductors or inhibitors...) factors; these recent advances have led to improved individual adjustment of theophylline dosage using serum concentration assays if needed. Theophylline is used in acute attacks and in maintenance therapy of asthma. Main side effects are digestive intolerance and, with toxic doses, neurologic disorders. Atropine-like drugs inhibit the effects of the parasympathetic reflex which results from stimulation of receptors by irritation of the respiratory tract, through the action of mediators. In this group, ipratropium is the only drug given in aerosols; this, together with its pharmacologic specificity, contributes to its tolerance. In some instances, the bronchodilating effect of ipratropium bromide is comparable to that of sympathomimetics.

Animals↗
PubMed1984

Reverse-phase liquid chromatography and pharmacokinetic study of two hydroxylated analogues of quinidine in dogs.

Two hydroxylated analogues of quinidine with antiarrhythmic properties, 3S-hydroxyquinidine and 3R-hydroxydihydroquinidine were assayed by reverse-phase high-performance liquid chromatography. The analytical technique uses plasma protein precipitation and direct injection on a C18 column, with an isocratic mobile phase and spectrofluorometric detection. 3R-Hydroxyquinidine is employed as the internal standard. Linearity is verified up to 5 mg/L for the two drugs; concentrations between 0.5 and 2.5 mg/L were measured with a CV of 0.5-2.07% for a given day and a sensitivity limit of 50 micrograms/L. Plasma concentration-time profiles and pharmacokinetic parameters in three dogs are presented after intravenous or oral administration. A significant difference is observed in terminal half-life, terminal rate constant, and total clearance of the two polar analogues of quinidine.

Administration, Oral↗
PubMed1984

Synthesis of a novel series of (aryloxy)propanolamines: new selective beta 2-blocking agents.

A new family of beta-blocking drugs is described. The originality of the new molecules lies in their functionalized hydrophobic folded structure, the basic part of which contains a benzocyclobutene ring. Excellent beta 2-blocker selectivity has been obtained with some of these compounds. Interestingly, this selectivity was not modified toward beta 1-blocker activity by introduction of the usual beta 1 inducer groups.

Adrenergic beta-Antagonists↗
PubMed1984

Effects of five different organic calcium antagonists on guinea-pig isolated trachea.

The relaxant effects of five organic calcium antagonists (nicardipine, diltiazem, PY 108068, verapamil and bepridil) on guinea-pig isolated trachea were tested against contractions induced by acetylcholine, histamine, 5-hydroxytryptamine, potassium chloride (KCl) and tetraethylammonium (TEA) in a medium containing the normal amount of calcium and against calcium dose-response curves in a calcium-free, potassium-enriched medium. These effects were compared with those of spasmolytic or specific acetylcholine or histamine antagonists. In contrast to the other drugs tested, organic calcium antagonists exerted a specific inhibitory effect on KCl- and TEA-induced contractions. Their degree of activity was in the order: nicardipine greater than diltiazem greater than PY 108068 greater than verapamil greater than bepridil. All calcium antagonists inhibited calcium dose-response curves at similar concentrations. Organic calcium antagonists therefore seem to exert a specific inhibitory effect on depolarizing agents in the guinea-pig isolated trachea, unlike other tissues, notably some vascular smooth muscles.

Animals↗
PubMed1983

Effects of diltiazem and other Ca2+ antagonists on guinea-pig tracheal muscle.

The effects of diltiazem and 3 other Ca2+ antagonists (verapamil, nicardipine, bepridil) were studied on isolated guinea-pig tracheal preparations which were contracted with several agonists. Assessment of the contractile agonists was performed under physiological conditions as well as in Ca2+-depleted solutions. The order of potency of the contractile agonists was LTD4 greater than ACh greater than 5-HT greater than Hist greater than BaCl2 greater than TEA greater than KCl. The efficacy of the physiological agonists ACh, Hist and LTD4 was moderately depressed in Ca2+-free solutions while the responses to non-specific agonists and 5-HT were markedly reduced. Diltiazem and verapamil reduced basal tone at concentrations greater than or equal to 10(-4) M. Diltiazem displaced all agonist concentration-effect curves to the right. The four Ca2+ antagonists studied had a marked effect on non-physiological agonists as compared to that on physiological agents. Increasing Ca2+ concentration only partially reversed the inhibitory effect of diltiazem.

Airway Resistance↗
PubMed1983

Determination of trimethoprim, sulphamethoxazole and its N4-acetyl metabolite in biological fluids by high-performance liquid chromatography.

A normal-phase high-performance liquid chromatographic method was developed to determine therapeutic concentrations of trimethoprim, sulphamethoxazole, and its N4-acetyl derivative in biological fluids. The compounds are extracted at pH 6.2 using ethyl acetate--chloroform in a single extraction. The detection limit is 15 ng/ml for trimethoprim, 20 ng/ml for sulphamethoxazole, and 10 ng/ml for its N4-acetyl metabolite. The method is rapid, sensitive, precise, and well suited to clinical pharmacokinetic investigations.

Aged↗
PubMed1983

Bronchopulmonary effects of clonidine on the bronchomotor responses of the guinea-pig.

In conscious guinea pigs, clonidine (10 and 100 micrograms/kg i.v.) lowered diastolic (-7.9 +/- 3.5 and -12.4 +/- 5.2%) and systolic (-8.6 +/- 3.0 and -11.9 +/- 4.2%) arterial pressure and reduced heart rate (-14.5 +/- 3.9 and -27.7 +/- 3.8%), but did not significantly modify pulmonary airway resistance. Hypotension was suppressed by yohimbine and bradycardia was partially suppressed by atropine and yohimbine, which demonstrates in this animal an alpha 2-adrenergic effect for hypotension and a mixed cholinergic and alpha 2-adrenergic effect for bradycardia. Clonidine (10 and 100 micrograms/kg i.v.) enhanced the bronchoconstrictor effects of histamine 20 micrograms/kg (+80.0 +/- 22.5 and 89.1 +/- 26.5%), acetylcholine 25 micrograms/kg (+66.4 +/- 19.8 and +95.4 +/- 25.4%) and serotonin 15 micrograms/kg (+68.5 +/- 23.2 and +81.4 +/- 34.1%). The duration of this effect was comparable to that of the hypotensive and cardiac effects of clonidine. The effects of clonidine were suppressed after pretreatment with propranolol, reserpine or pentobarbitone, all drugs which enhance the bronchoconstrictor effect of ACh. Yohimbine (1 mg/kg), piperoxan (0.3 mg/kg) or prazosin in high dosage (0.3 mg/kg) inhibited the potentiation by clonidine of ACh-induced bronchoconstriction, whereas prazosin in lower doses (0.03 mg/kg) or AR-C 239 (0.05 mg/kg) had no action. A specific involvement of alpha 2-adrenoceptors stimulated by clonidine with subsequent reduction of the adrenergic activity associated with bronchospasm could therefore be demonstrated in the conscious guinea-pig during bronchomotor reactions.

Acetylcholine↗
PubMed1983

Pharmacokinetic studies of rifampicin in the elderly.

The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1.72 mg L-1 and 4.09 +/- 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmax value (1.93 +/- 0.53 mg L-1) and t 1/2 beta value (4.65 +/- 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 +/- 0.0036 L h-1) and the amounts of RMP (20.7 +/- 9.9 mg) and DA-RMP (13.3 +/- 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.

Aged↗
PubMed1983

Pharmacokinetics of ketoprofen in the elderly.

Pharmacokinetic constants of ketoprofen (Orodis, Profenid) were determined in 10 young adults (24.9 +/- 1.3 years) and seven elderly patients (86.3 +/- 2.4). Following oral administration of a 150 mg dose of ketoprofen, no difference in tmax was observed between the two groups. However, compared with younger subjects elderly patients showed a significant increase in t1/2,z (2.72 +/- 0.22 vs 1.77 +/- 0.16 h; P less than 0.01) and AUC (70.4 +/- 6.4 vs 29.13 +/- 2.02 mg l-1 h; P less than 0.001), a non-significant reduction of Vd/F per kg bodyweight (0.145 +/- 0.016 vs 0.213 +/- 0.028 l kg-1) and a decrease in total clearance CLT/F (0.037 +/- 0.002 vs 0.071 +/- 0.004 l h-1 kg-1, P less than 0.05). These results suggest that the glucuroconjugation of ketoprofen is slowed down by age.

Adult↗
PubMed1983

Sodium cromoglycate, verapamil and nicardipine antagonism to leukotriene D4 bronchoconstriction.

1--The effects of nicardipine, verapamil and sodium cromoglycate (SCG) on the increase in pulmonary airway resistance(RAw) and decrease in pulmonary dynamic compliance (CDyn) induced by leukotriene D4 (LTD4) 0.5 micrograms kg-1 and acetylcholine (ACh) 3 micrograms kg-1 were investigated in anaesthetized guinea-pigs. The effects of these three agents on the contractile effects of LTD4 and ACh were tested on isolated tracheal preparations of the guinea-pig. 2--Nicardipine and verapamil (0.3 and 1 mg kg-1), as well as SCG (3 and 10 mg kg-1), partially but significantly inhibited the effects of LTD4 on RAw. Partial inhibition of the effect of LTD4 on CDyn was only observed with verapamil (0.3 and 1 mg kg-1). Nicardipine and verapamil had no effect on ACh-induced bronchoconstriction in vivo. 3--In concentrations higher than 10(-5) M, nicardipine and verapamil inhibited the contractile effects of LTD4 and ACh on guinea-pig isolated trachea. SCG had no effect on this preparation. 4--These results suggest that nicardipine, verapamil and SCG partially reduce the component of bronchoconstriction associated with stimulation of irritant receptors by LTD4. However, the site and mechanism of action of Ca2+-entry antagonists remain uncertain.

Airway Resistance↗
PubMed1982

The effects of atropine on anaphylactic shock in the guinea-pig.

The effects of atropine, 2 mg/kg i.v., on anaphylactic shock were studied in guinea-pigs sensitized to ovalbumin. Atropine only moderately reduced (--31%) the increase in pulmonary resistance observed and slightly prolonged (+26%) the survival time in pretreated animals compared with controls. These effects, however, were no statistically significant. The drug temporarily improved ventilation but had no influence on haematosis. On the other hand, atropine significantly reduced the amount of histamine released (--60%) and of GMPc synthetized in the lung (--21%). The levels of AMPc and prostaglandins E1, E2 and F2 alpha remained comparable to those of control animals. These results suggest that the reflex-induced action of the cholinergic system during anaphylaxis primarily affects large-calibre airways and that the role of acetylcholine in severe reactions is moderate when compared with the direct action of other mediators.

Airway Resistance↗
PubMed1982

Contribution of prostaglandins and thromboxanes to the adenosine and ATP-induced contraction of guinea-pig isolated trachea.

1 In in vitro experiments adenosine 5'-triphosphate (ATP) and adenosine were found to exert different effects on the guinea-pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 x 10(-6) M) or was at resting tone. 2 ATP and adenosine (10(-5) and 10(-3) M) were equipotent in relaxing the precontracted guinea-pig trachea, since concentrations of 1.09 +/- 0.35 and 0.39 +/- 0.16 mM respectively reduced by 25% the ACh-induced contraction. 3 ATP and adenosine (10(-5) and 10(-4) M) caused a moderate contraction of the guinea-pi trachea under resting tone. This effect was antagonized by inhibitors of cyclo-oxygenase (indomethacin 10(-6) M, aspirin 0.3 x 10(-3) M and 3 x 10(-3) M) and of thromboxane synthetase (nictindole 10(-7) M, imidazole 5 x 10(-5) M), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.

Adenosine↗
PubMed1981

Histamine-releasing properties of hydroxy-9-methyl-2-ellipticinium acetate.

Previous work on Hydroxy-9-methyl-2-ellipticinium acetate indicated a bronchoconstrictor activity which could be partially offset by antagonists of the H1 histamine receptors, and the absence of any direct effect on smooth muscle. OH-9-CH3-2-E at concentrations of 10 micrograms/ml and 500 micrograms/ml produced a moderate and a variable release of histamine when placed in contract with whole human blood and lung fragments, respectively. In addition, at a dose of 3 mg/kg in the guinea pig, pulmonary airway resistance was raised and the blood histamine level lowered. A significant correlation was found between these two effects. These results demonstrate that OH-9-CH3-2-E possesses a histamine-releasing potency which is partly responsible for its bronchial effects, implying that precautions may have to be taken when it is used as a therapeutic agent in sensitive subjects. However, the moderate intensity of this potency has not so far precluded therapeutic use of the preparation.

Airway Resistance↗
PubMed1981

[The pharmacokinetics of isoniazid in children (author's transl)].

The purpose of this study, which involved 134 children aged between 0.5 and 17 years, was to investigate the metabolism of isoniazid (INH) in children and to provide guide-lines for dosage. The distribution of slow (55,5%) and fast (44,5%) acetylators was the same in children as in adults. However, the mean of INH inactivation index were lower (0.23 and 0.48) while distribution volumes, (1.30 +/- 0.06 and 1.57 +/- 0.17 1/kg) and total plasma clearances (5.39 +/- 0.43 and 14.7 +/- 1.5 ml/Kg/min) were higher than in adults. Plasma half-lives were similar in children and adults. These results indicate that INH is more rapidly metabolized in children owing, it is suggested to a higher liver weight : body weight ratio and to a more pronounced first pass effect. The doses of INH therefore must be higher in children and strictly adapted to each individual.

Adolescent↗