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Biomedical subjects

G M Frigo

Publications and source records attributed to G M Frigo.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effect of chronic anticonvulsant monotherapy on lymphocyte subpopulations in adult epileptic patients.

Sixty-five patients undergoing long-term monotherapy for at least 3 months with phenytoin, carbamazepine or phenobarbital were screened for lymphocyte and immunoglobulin abnormalities. In 57% of patients the duration of therapy was longer than 12 months. The control subjects were matched for sex and age and none of them was taking drugs. The average serum immunoglobulin (IgG, IgA, IgM) values did not differ in control and patient groups. A significant decrease of OKT4+ cells was seen with all drugs, while other lymphocyte subpopulations were differently affected depending on the drug used. It is concluded that long-term single-drug treatment with phenytoin, carbamazepine and phenobarbital exhibits immunosuppressant effects through a complex action which involves more than one lymphocyte subpopulation. Moreover, the possible interference of the disease state with the immune functions of epileptic patients is discussed.

Adolescent↗
PubMed1984

Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation.

The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon. The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine greater than noradrenaline greater than methoxamine greater than isoprenaline for the inhibition of peristalsis and isoprenaline greater than noradrenaline greater than methoxamine greater than clonidine for the relaxation of circular muscle. Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both alpha and beta receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release. Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

Pharmacokinetics of prednisone and its metabolite prednisolone in children with nephrotic syndrome during the active phase and in remission.

The kinetics at steady state of prednisone and its metabolite prednisolone were determined in nine nephrotic children during the active phase of the disease and in remission. There were no differences in serum prednisone levels between the two occasions. Prednisone levels were lower than prednisolone levels. Total serum prednisolone levels were significantly lower during the active phase than in remission (AUC: 2452 +/- 207 vs 3392 +/- 293 ng ml-1 h respectively). Half-life values were similar on both occasions. The binding of prednisolone to serum proteins was markedly impaired during the active phase as compared to the remission. Free fraction values correlated positively with total drug concentration. A negative correlation between free fraction and serum albumin level was found during the active phase. Free prednisolone levels during the active phase did not differ significantly from those observed during remission (AUC: 937 +/- 128 vs 847 +/- 81 ng ml-1 h respectively). These data indicate that pharmacokinetic changes are unlikely to be responsible for alterations in steroid responsiveness in nephrotic patients with hypoalbuminaemia.

Adolescent↗
PubMed1984

Pharmacokinetics of valproic acid in the elderly.

The kinetics of a single oral dose of sodium valproate was studied in six healthy elderly patients (age 68-89 years) and six young control subjects (age 24-26 years). The profiles of total plasma valproic acid (VPA) concentrations were very similar in the elderly and in the young. Half-lives (15.3 +/- 0.7 s.e. mean in the elderly vs 13.0 +/- 1.0 h in the young), volumes of distribution (0.16 +/- 0.01 l/kg in the elderly vs 0.14 +/- 0.01 l/kg in the young) and clearance (7.5 +/- 0.9 ml h-1 kg-1 in the elderly vs 7.7 +/- 0.6 ml h-1 kg-1 in the young) did not differ significantly between the two groups. Free VPA concentrations were significantly increased in the elderly. The clearance of the free drug (intrinsic clearance) was reduced from 127.0 +/- 12 ml h-1 kg-1 (control value in the young) to 77.7 +/- 5.5 ml h-1 kg-1 (P less than 0.02). Free VPA fraction was 9.5 +/- 0.6% in the elderly and 6.6 +/- 0.5% in the young (P less than 0.02). These findings suggest that the pharmacokinetic alterations of VPA in old age are complex and include at least two separate mechanisms: a decrease in plasma protein binding and a reduction of drug metabolizing capacity resulting in decreased clearance of free drug by the liver.

Adult↗
PubMed1984

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations.

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.

Adult↗
PubMed1984

5-hydroxytryptamine desensitization fails to modify GABA-induced inhibitory responses in the guinea-pig colon.

In segments of guinea-pig colon, treated with 1 microM hyoscine, a 5-HT desensitization procedure that decreased the potency of 5-HT 41-fold in relaxing the longitudinal musculature, failed to modify the non-adrenergic GABA-induced inhibitory responses, suggesting that the action of GABA in this preparation is not 5-HT-mediated. These results are at variance with those obtained in the guinea-pig ileum where 5-HT seems to play a role in GABA-induced cholinergic contractions.

Animals↗
PubMed1983

5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum.

GABA (3--100 microM) and 5-HT (0.03--30 microM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. The contractile response to GABA was antagonized by hyoscine (2.2 microM). TTX (0.7 microM), bicuculline (3 microM), furosemide (25 microM) and desensitization to GABA itself, while hexamethonium (20 microM) and methysergide (20 microM) were without effect. The contractile response to 5-HT was antagonized by hyoscine (2.2 microM), TTX (0.7 microM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 microM), hexamethonium (20 microM), furosemide (25 microM) and methysergide (20 microM). A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 microM) concentrations of GABA. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.

Animals↗
PubMed1983

Reduction of phenytoin clearance caused by cimetidine.

The effect of cimetidine on the disposition kinetics of phenytoin was investigated in 7 healthy volunteers. Each subject received a single intravenous dose of phenytoin on two occasions, in the control state, and during concurrent treatment with cimetidine 1 200 mg/day for 6 days. A slight but statistically significant decrease both in the rate of elimination and total body clearance of phenytoin was observed during the administration of cimetidine. The effect is probably due to inhibition of metabolism.

Adult↗
PubMed1983

Penicillin CSF levels following intravenous therapy in syphilitic patients.

Serum and CSF levels of penicillin have been determined in 13 syphilitic patients treated with relatively high doses of penicillin G by the intravenous route. Wide individual variability in the CSF/serum concentration ratio was observed. In all patients the concentration of the antibiotic in the CSF was equal to or greater than 0.03 IU/ml., which is considered to be the minimal therapeutic concentration. The potential clinical usefulness of different therapeutic regimens in the treatment of neurosyphilis is discussed.

Adult↗
PubMed1983

Purine receptors in the guinea-pig internal anal sphincter.

1 In the isolated internal anal sphincter of the guinea-pig, adenosine 5'-triphosphate (ATP) and adenosine induced a concentration-dependent and tetrodotoxin-insensitive relaxation. 2 Pretreatment with theophylline (25-50 microM) had no significant effect on the concentration-response curves obtained with either purine compound. 3 Reactive blue 2 (25-100 microM) shifted the curve to ATP to the right in a dose-dependent fashion leaving that to adenosine unaltered. The antagonism appeared to be non-competitive. 4 Neither reactive blue 2 nor purine receptor occupation by ATP or adenosine altered the electrically-induced non-adrenergic, non-cholinergic inhibitory response. 5 The actions of ATP and adenosine in the guinea-pig internal anal sphincter appear to be mediated by separate receptors. These receptors are not involved in the nerve-mediated relaxation.

Adenosine↗
PubMed1982

Effects of desensitization to adenosine 5'-triphosphate and adenosine on non-adrenergic inhibitory responses in the circular muscle of rabbit colon.

An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 microM) of these compounds. The desensitization was specific and reversible after prolonged washing. It could be overcome by increasing the concentrations of the purine agonists. Dipyridamole potentiated the non-adrenergic inhibition in response to transmural stimulation but failed to influence the caudad relaxation evoked by radial distension. Desensitization to ATP and adenosine (and to ATP + adenosine simultaneously) did not affect the non-adrenergic inhibition in response to radial distension or transmural stimulation. These results suggest that neither ATP nor adenosine are the final transmitters mediating the non-adrenergic inhibitory responses in the distal colon of the rabbit.

Adenosine↗
PubMed1982

Motor responses of rat stomach in vitro after subacute oral administration of trithiozine.

The effects of ten days' oral treatment with 200 mg/kg/d of 4-(3,4,5-trimethoxythiobenzoyl)tetrahydro-1,4-oxazine (trithiozine) on the mechanical responses of rat stomach in vitro have been studied. Gastric muscular excitation due to vagal stimulation was partially reduced in the trithiozine-pretreated animals, while the amount of acetylcholine (Ach) released both at rest conditions and in response to field stimulation was similar in both controls and drug-pretreated rats. Also muscular responses induced by dopamine (DA) and by serotonin (5-HT) were of similar degree in both groups of rats. On the contrary, the nonadrenergic and non-cholinergic inhibitory response evoked by vagal stimulation in the presence of muscarinic and alpha- and beta-adrenergic receptor blockade, respectively, was enhanced in the drug-pretreated animals. Moreover, trithiozine pretreatment caused an increase of spontaneous motor activity and a remarkable degree of potentiation of the contractile response to prostaglandins (PGs), both exogenously applied or endogenously released by ATP. Our results give further evidence that trithiozine has no anticholinergic activity and that some therapeutic properties of the molecule could be accounted for by an involvement of endogenous PGs.

Acetylcholine↗
PubMed1980

Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects.

The effect of sodium valproate (400 mg three times daily) on the disposition kinetics of intravenous phenytoin (250 mg) was investigated in seven normal subjects. After valproate, the free (unbound) fraction of phenytoin in serum rose from 9.6 +/- 0.9% (SD) to 15.6 +/- 1.4% on average (p < 0.001). The effect was associated with an increase in systemic clearance and apparent volume of distribution of total drug. There was a strong positive correlation between percent increment in each of these parameters and percent increment in unbound drug in serum. Free phenytoin concentration in serum and phenytoin concentration in saliva increased during valproate administration. As a result, both the clearance and the apparent volume of distribution of free drug were reduced. There was an increase in the renal excretion of unchanged phenytoin during valproate administration, but the effect was too small to have an appreciable influence on the overall clearance of the drug. There were no consistent changes in the excretion of the major metabolite 5, p-hydroxyphenyl, 5-phenyl, hydantoin (pHPPH), in the urine. These results suggest that valproic acid may have two separate and opposing effects on phenytoin disposition: (1) displacing phenytoin from plasma protein binding sites, thereby enhancing the systemic clearance of total drug, and (2) inhibiting phenytoin metabolism, thereby increasing the concentration of free drug in the serum.

Adult↗
PubMed1980

Antiepileptic drug therapy and plasma levels in 2500 patients from Northern Italy.

The antiepileptic drug therapy of 1912 patients coming from various neurological clinics of Northern Italy has been evaluated in a collaborative survey. The following epidemiological data have been analysed: incidence of the various seizures types, according to the International Classification (Gastaut, 1969), in relation to the age; drug choice and therapeutic schedules in relation to the seizure type and to the age; number of drugs administered in various age and seizure groups; side effects in relation to type, number and plasma concentrations of the administered drugs. The analysis of the drug plasma level determinations, carried out either with gas-chromatographic methods or with the EMIT system, was effected in order to evaluate the number of patients who were under, in or over the suggested therapeutic ranges, the influence of age on drug disposition and the modifications of the drug plasma levels due to drug interactions.

Adolescent↗