Search PubMed⌕ Search

Biomedical subjects

A Bobik

Publications and source records attributed to A Bobik.

At least 163 records · Page 9Linked to original sources
PubMed1980

Norepinephrine kinetics in patients with idiopathic autonomic insufficiency.

The rates of norepinephrine release into plasma and removal from plasma were studied in patients with idiopathic peripheral autonomic insufficiency (sympathetic neuronal dysfunction), as it was thought that plasma norepinephrine concentration alone inadequately quantifies the degree of sympathetic nervous underactivity in this disorder. In four patients with autonomic insufficiency, clearance of norepinephrine from the circulation was slowed, 1.69 +/- 0.44 liters/min, compared with 2.80 +/- 0.73 liters/min in 10 normal subjects (P less than 0.05). As a consequence, despite a 60% lower norepinephrine apparent secretion rate, 0.19 +/- 0.12 microgram/m2 per min vs. 0.54 +/- 0.20 microgram/m2 per min, the plasma norepinephrine concentration was near normal. The plasma concentration of neurotransmitter does not provide a valid index of sympathetic nervous tone in this disorder in which removal of norepinephrine from the circulation is slowed.

Dysautonomia, Familial↗
PubMed1979

Comparison of effectiveness of timolol administered once a day and twice a day in the control of blood pressure in essential hypertension.

The effects of a single dose and of two equally divided doses of timolol were compared in a double-blind trial in 15 patients with essential hypertension. The amount of timolol per day remained constant for each patient, but individual patients received different amounts (from 10 mg to 30 mg/day). Timolol combined with a diuretic produced similar lowering of blood pressure in patients who required 10 mg, 20 mg or 30 mg of timolol per day when given either as one dose or in two equal doses. Plasma concentrations of timolol were high enough to be a major contributing factor to the long duration of the hypotensive response.

Adult↗
PubMed1979

Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.

1 Pharmacokinetics of pindolol were studied in normal subjects given 5, 10 and 20 mg orally and 3 mg i.v. Plasma half time was 2.9 +/- 0.3 (s.e. mean) h for both routes; peak drug levels occurred 1--2 h after ingestion and bioavailability was 53%. Plasma protein binding was 38% and was independent of plasma concentration; the drug was not concentrated in the red cell. 2 Work-heart rate regression lines were calculated from resting heart rate and three grades of 'steady-state' exercise standardized for the maximum work capacity (Wmax) of each subject. The equation was characterized by slope and HR50 (calculated heart rate at 0.5 Wmax). 3 After giving 5 mg i.v. pindolol to produce maximum cardiac beta-adrenoceptor blockade there were differences in inhibition of resting heart rate, slope, HR50 and maximum heart rate suggesting differences in sympathetic components. However, estimates of the degree of inhibition were closely similar for each variable when determined before and after atropinization indicating that the accuracy of estimation was independent of the level of vagal activity. 4 After oral pindolol peak inhibition of resting heart rate, slope and HR50 coincided with peak plasma concentration. Peak reduction of resting heart rate was greatest at the lowest dose, but inhibition of slope and HR50 were similar at all doses. 5 The different heart rate parameters recovered at different rates. After 24 h slope had returned to control, and the residual inhibition of HR50 reflected residual beta-adrenoceptor blockade of resting heart rate, as demonstrated by a shift in isoprenaline-heart rate relationship. 6 Inhibition of HR50 and other exercise parameters were 20% less in the concentration range 5--20 ng/ml than peak inhibition obtained in the range 21--160 ng/ml. The higher potency of pindolol compared with propranolol can be accounted for by the difference in protein binding.

Adult↗
PubMed1979

Absorption and excretion of rapid and slow release oxprenolol and their effects on heart rate and blood pressure during exercise.

1. Plasma concentrations and heart rate and blood pressure effects of 160 mg oxprenolol as standard rapid release (RR) and slow release (SR) tablets were compared in healthy volunteers. Peak plasma concentrations were lower with SR tablets than with RR tablets and the peak was delayed. 2. Absorption of oxprenolol was described adequately by first order kinetics with both preparations. The apparent half-life of absorption was 0.40 h with RR and 2.4 h for the SR formulation. The apparent elimination half-life of oxprenolol was about 2 h. Relative bioavailabilities of the two formulations were similar. 3. The effectiveness of oxprenolol RR and SR were assessed by their effects on heart rate in severe exercise (EHR) and also by their effects on blood pressure at rest and during exercise. 4. Maximum reductions in these variables coincided with peak oxprenolol concentrations. The effects on EHR and blood pressure parameters had a distinct time course but there was no difference between the time course of inhibition of each variable for the two formulations over 24 h.

Adult↗
PubMed1978

Investigation of cardiac beta-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol.

1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites. The beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine competed for binding with potencies paralleling their pharmacological potencies as beta-adrenergic effectors. The dissociation constant for binding of IIP was 4--5 nM as measured either by direct binding studies or by its inhibition of isoproterenol stimulated adenylate cyclase. Binding was saturable with 0.06 pmoles of IIP per mg of membrane protein binding at saturation. 125IIP is a high affinity, high specific activity ligand suitable for use as a selective probe for the detection and quantitation of cardiac beta-receptors. Its introduction should help solve the problems involved in the investigation of myocardial beta-adrenergic receptors.

Adenylyl Cyclases↗
PubMed1978

Guanethidine-induced vasodilatation in the rabbit, mediated by endogenous histamine.

1 The effects of guanethidine (0.5-4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanesthetized rabbits subjected to "total" autonomic block. 2 Evidence that this response was mediated by histamine release was that (a) 3H-labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine-induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2-antagonist burimamide. 3 There was good correlation between the [3H]-histamine ;elease and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine. 4 Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine. 5 The guanethidine vasodilator response was not influenced by the H1-antagonist mepyramine or by the other H2-antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2-antagonists.

Animals↗
PubMed1977

Drug analysis in the overdosed patient: its application to clinical toxicology.

A study was made of 187 patients suffering from overdosage by means of clinical records and drug analysis. Drugs were detected in 152 patients. The groups of drugs most frequently involved in these patients were sedatives (51-7%), tricyclic antidepressants (21-8%) and analgesics (11-2%). This overall pattern differed little from that determined by clinical diagnosis. However, discrepancies between clinical diagnosis and laboratory analysis were found in 43 patients. A retrospective assessment was made from clinical records of the influence of drug assay results upon clinical management. Decisions as to the need for admission to hospital and decisions relating to the management of patients suffering from overdoses of analgesics and tricyclic antidepressants were aided by drug analysis.

Acetaminophen↗
PubMed1977

Inhibitors of hepatic mixed function oxidase. 3. Inhibition of hepatic microsomal aniline hydroxylase and aminopyrine demethylase by 2,6- and 2,4-dihydroxyphenyl alkyl ketones and related compounds.

A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor. In the 2,4 series, activity against aniline hydroxylase was poor or absent in most cases. tthe most potent inhibitor was 5-ethyl-2,4-dihydroxyacetophenone (31). In contrast, high activity against aminopyrine demethylase was frequently displayed in this series, 3,5-dibromo-2,4-dihydroxypropiophenone (36) showing greatest inhibitory potency. The effects of some compounds on hexobarbital sleeping times and zoxazolamine paralysis times in mice were also examined.

Acetophenones↗
PubMed1977

Leakage of dl-propranolol from cerebrospinal fluid to the bloodstream in the rabbit.

Intracerebroventricular (i.c.v.) injection of 500 microgram of dl-propranolol in the conscious rabbit in a rise in mean arterial pressure followed by a small but significant fall (3.2 +/- 1.4 mm Hg between 2 and 4 hours after injection), as has been observed by others. The same dose injected i.v. resulted in a lowering of mean arterial pressure of 6.0 +/- 2.4 mm Hg between 2 and 4 hours after injection. After i.c.v. injection there was a rapid rise in plasma propranolol concentration. Ten minutes after i.c.v. injection the concentration of 80% of the level reached after giving the same dose i.v. After i.c.v. injection there was significant blockade of cardiac beta adrenoreceptors for at least 2 hours. This blockade was determined from the degree of attenuation of isoproterenol-induced tachycardia in rabbits subjected to presynaptic sympathetic nerve block with guanethidine and to vagal block with methscopolamine. Because of the rapid leakage of propranolol from cerebrospinal fluid to plasma it is not possible by means of the technique of i.c.v. injection of the drug to differentiate between central nervous and systemic mechanisms contributing to the lowering of blood pressure.

Animals↗
PubMed1976

Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits.

1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.

Adrenergic beta-Antagonists↗
PubMed1976

Cardiovascular complications due to pheniramine overdosage.

Cardiovascular toxicity including ventricular extrasystoles associated with pheniramine overdosage has been documented in the absence of factors recognised to aggravate this toxicity. The presence of pheniramine and the absence of other compounds was established using analytical techniques. It is concluded that patients with pheniramine overdosage should be treated exercising the same precautions as with tricyclic overdosage. Several sudden and unexpected deaths have occurred due to pheniramine overdosage in both adults and children. The cause of death in each case was not known. The purpose of this report is to document clinical features of pheniramine overdosage, in particular previously unsuspected cardiovascular toxicity manifesting as clinically significant ventricular arrhythmias. Pheniramine was positively identified in the overdosed patient, and the presence of other agents excluded.

Adult↗
PubMed1976

Action of propranolol on arterial pressure and on cardiovascular reflexes.

In the rabbit, administration of 500 mug (+/-) propranolol into the lateral cerebral ventricle resulted in rapid leakage of drug into the blood. The drug produced a small reduction in blood pressure at 2 and 4 hours after injection but because of the rapid leakage, this could have been due to its peripheral actions. To investigate possible central mechanisms of action which were independent of peripheral effects, we tested the action of intravenously administered propranolol on the reflex rise in TPR evoked in rabbits by graded Valsalva-like manoeuvres. This was performed in unanaesthetised rabbits with Doppler flowmeters for measuring cardiac output. Graded expiratory pressures (EP) were applied to the inlet and outlet tubes of the tracheotomised animal's respiratory valve and to the cuff around their thorax and abdomen. Administration of propranolol at two levels (168 +/- 35 ng/ml, and 240 +/- 33 ng/ml) for 1 hour had no effect on slope and threshold of the EP-TPR relationship. By contrast to the minimal effects on the reflex with propranolol, the EP-related rise in TPR was attenuated by clonidine. We conclude that propranolol does not lower blood pressure in the rabbit by attenuating sympathetic constrictor activity.

Animals↗
PubMed1975

Inhibitors of hepatic mixed function oxidases. I. The metabolism of 2,6-dihydroxy-,2-hydroxy-6-methoxy- and 2,6-dimethoxyacetophenones.

1. 2,6-Dihydroxyacetophenone, its mono- and di-methyl ethers are inhibitors of hepatic mixed function oxidases. The dimethyl ether is a competitive inhibitor of aminopyrine demethylase with the others displaying mixed kinetics. The metabolism of all three ketones has been studied. 2. 2,6-Dihydroxyacetophenone is excreted unchanged and as conjugates. 3. 2-Hydroxy-6-methoxyacetophenone is largely excreted unchanged and conjugated but small amounts of the 3- and 5-hydroxylated derivatives are formed. 4. 2,6-Dimethoxyacetophenone is demethylated to 2-hydroxy-6-methoxy-acetophenone. In addition 3-hydroxy-2,5-dimethoxyacetophenone and 2,3-dihydroxy-6-methoxyacetophenone were identified as metabolites. 5. Quantitative data on the excretion of metabolites were obtained with 14C-labelled ketones.

Acetophenones↗