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Biomedical subjects

B Beermann

Publications and source records attributed to B Beermann.

At least 55 records · Page 3Linked to original sources
PubMed1987

Adenosine-provoked angina pectoris-like pain--time characteristics, influence of autonomic blockade and naloxone.

In a study to characterize the time characteristics and the influence of blockade of beta, cholinergic and opioid receptors on the chest pain induced by adenosine, this agent was given as a bolus into a peripheral vein of six healthy volunteers (4 men) 24-45 years of age. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (1/3, 2/3, and a full maximum tolerable dose) and three doses of placebo were given as single blind doses in randomized order. Thereafter metoprolol (10 mg to males, 8 mg to females), followed by 1 mg atropine and then 0.4 mg naloxone were given intravenously. After each agent the test procedure was repeated. Heart rate and atrio-ventricular blocks were recorded by electrocardiography and respiration by dynamic spirometry. One minute after each dose of adenosine, the chest pain was scored. The maximum tolerable dose of adenosine was 8.0-15.9 mg. All subjects experienced angina pectoris-like pain. Following injection, onset of respiratory stimulation, AV-block and chest pain occurred after 14 +/- 4.0, 19 +/- 5.4 and 21 +/- 6.4 s, the differences being highly significant. Maximal respiratory stimulation occurred after 18 +/- 4.6, not statistically different from the onset of AV-block which in its turn occurred earlier (P less than 0.005) than the time for maximal central chest pain, 29 +/- 7.8 seconds. Metoprolol induced a 20% slowing of heart rate. After atropine there was a 30% faster heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

Clinical pharmacokinetics of some newer diuretics.

Several new diuretics have recently been developed. This review summarises the published knowledge about some of them. Azosemide is a loop diuretic. The bioavailability is about 15% and it has a half-life of 2 to 3 hours. Renal and non-renal clearance are 1.32 and 5.4 L/h, respectively. Etozolin is also a loop diuretic. It is rapidly metabolised to the active metabolite, ozolinone. The gastrointestinal uptake of etozolin is almost complete. The plasma half-life of etozolin and ozolinone are 2 and 10 hours, respectively. The compounds are mainly eliminated as metabolites. Renal and liver impairment do not seem to change the pharmacokinetics. Fenquizone has properties similar to the thiazides. The plasma half-life is approximately 17 hours. Apparent volume of distribution averaged 686 L and renal clearance is 7.2 L/h. Indapamide acts predominantly on the proximal segment of the distal tubule and also has direct vasodilatory effects. Gastrointestinal uptake is at least 80%. The drug binds highly to carbonic anhydrases of red blood cells. Protein binding is about 80%, while terminal plasma half-life is 15 hours and the apparent volume of distribution 25 L. Renal clearance is 0.3 L/h and non-renal clearance 0.9 L/h. Several metabolites have been described, of which one major metabolite is pharmacologically active. Muzolimine is a loop diuretic. Its uptake is almost complete, but decreased substantially by food. The protein binding is about 65%, the apparent volume of distribution is about 1 L/kg and average terminal half-life 10 to 20 hours. Elimination is mainly non-renal, and non-renal clearance ranges between 0.5 and 1.32 L/h. The pharmacokinetics of the drug do not seem to be changed in cardiac failure. Terminal plasma half-life is essentially unchanged in patients with renal failure, except in those with very severe reduction of glomerular filtration rate. Piretanide is a loop diuretic which is about 6 times as potent as frusemide (furosemide). Its bioavailability is most likely complete in healthy subjects and in renal patients. Protein binding in healthy subjects is about 95%. The plasma half-life of the drug is about 1 hour and apparent volume of distribution averages about 17 L. Renal and non-renal clearance are about 6 L/h, although renal clearance is decreased in renal failure: this decrease is correlated with glomerular filtration rate. Non-renal clearance is unchanged in renal failure, as is the apparent volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Diuretics↗
PubMed1987

Pharmacokinetic-pharmacodynamic relationship of piretanide in healthy and uremic subjects. Determinants of the diuretic effect of a loop diuretic.

The pharmacokinetics of the loop diuretic piretanide and its diuretic effects were studied in 6 healthy volunteers, 12 pre-dialysis (GFR 7-28 ml/min) and 10 dialysis patients (c-creat. 1-7 ml/min). Single doses up to 96 mg i.v. and orally were well tolerated and audiometry showed no hearing changes. Pharmacokinetic data showed rapid and almost complete absorption (bioavailability 92%) and a rapid elimination with renal clearance of 50% of the total 200 ml/min in the normals and renal clearance of about 50% of actual GFR in the patients. Extrarenal clearance was the same in normals and patients. The rapid extrarenal elimination reduces the risk of accumulation in renal patients but also reduces the active fraction of the dosage being cleared by the kidneys. Therefore, a high dosage and high plasma levels of piretanide were necessary for diuretic effect in uremic patients. The relation between the urinary piretanide excretion rate and the chloruretic effect was similar in normals and uremic patients; Cl- excretion increased 40 mMol per mg piretanide excreted.

Adult↗
PubMed1987

Some effects of metolazone on electrolyte transport.

Metolazone action was studied 1) in vitro on isolated operculum of Fundulus heteroclitus (active chloride transport) using an Ussing chamber (metolazone conc 500 microM) and in vivo 2) using the modified Sperber technique in the hen (metolazone infusion rate 0.75-1.2 micrograms/kg/min) and 3) in healthy volunteers using clearance techniques (metolazone infusion rate 10 mg/h). Metolazone reduced (p less than 0.05) short circuit current potential differences with 20% from average control values (p less than 0.05), while direct current resistance was unchanged. This is comparable to thiazide but much lower than loop diuretic effects. True tubular excretion fraction of metolazone before and after novobiocin (2.7 mumol/kg/min coinfusion averaged 14.1 and 4.5%, resp. (p less than 0.01; n = 8). Thus metolazone is partly eliminated by renal tubular secretion. However, the diuretic effect (sodium, chloride and potassium excretion)--and clearances of Cr51-EDTA and I125-Na-o-iodohippurate--were symmetrical, i.e. independent of metolazone urinary excretion rate, as previously shown for thiazides. Renal clearance of metolazone in healthy volunteers. (HPLC-method) averaged 173 +/- 20 ml/min (n = 8). Probenecid (1 g iv.) significantly reduced the renal clearance of metolazone to 33 +/- 7 ml/min and potassium excretion with maximum 30%, while diuretic and saluretic effects were significantly increased with maximum 30%. Thus, also in humans the diuretic effect of metolazone is not coupled to the urinary excretion rate of the drug, but suggests that its diuretic effect is elicited primarily from the peritubular side of the nephron. Probenecid apparently dissociates sodium from potassium excretion effects of metolazone. This implies a luminal, sodium-independent kaliuretic effect of the drug.

Adult↗
PubMed1986

Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.

In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors.

Adenosine↗
PubMed1986

Reduced bioavailability and effect of furosemide given with food.

10 healthy volunteers were given 40 mg furosemide p.o. with and without breakfast. The meal reduced the peak level of furosemide and decreased its bioavailability by approximately 30%. A heavy meal given to 5 of the subjects had no further effect. The reduced bioavailability caused a reduction in the diuretic effect.

Adult↗
PubMed1986

Thiazides and loop-diuretics therapeutic aspects.

Thiazides and compounds with similar models of action exert their most important renal effects on the cortical-diluting segment of the nephron, most likely from the peritubular side. In contrast, the most important site of action of loop-diuretics is the luminal side of the ascending part of the diluting segment. The different sites of action explain the clinically proven efficacious combination of thiazides and loop-diuretics in severe cardiac failure. Most thiazides and loop-diuretics are eliminated via renal tubular secretion, which leads to decreased renal clearance in patients with chronic heart failure (CHF) as their renal blood flow is decreased even if glomerular filtration rate (GFR) is maintained. A rational approach to enhance the effects of loop-diuretics is to combine them with drugs that increase renal blood flow, thereby increasing the rate of delivery of the drug to its site of action. Dilutional hyponatremia is an important complication of treatment with diuretics. An efficacious treatment of that condition seems to be a combination of loop-diuretics and ACE-inhibitors. Thiazides decrease the urinary excretion of calcium, while loop-diuretics have the opposite effect. The possibility of loop-diuretic induced osteopenia cannot be ruled out, which should be considered when choosing between thiazides and loop-diuretics for the treatment of mild to moderate CHF.

Benzothiadiazines↗
PubMed1986

A double blind comparison of naproxen and sulindac in female patients with heart failure.

The objective of this investigation was to study the effects of the two NSAIDs sulindac and naproxen on renal hemodynamics and excretion of water, salt and the prostacyclin metabolite 6-keto-PGF1 alpha in patients with well controlled congestive heart failure. Ten elderly females with congestive heart failure treated with oral furosemide were given four doses of sulindac and naproxen every twelve hours after a control day in a double-blind cross-over fashion. Naproxen significantly decreased the urinary excretion of water (19%), sodium (26%), chloride (26%), 6-keto-PGF1 alpha (76%) and decreased osmolal clearance by 18%. Sulindac had no significant effect on those parameters. There were no significant changes in glomerular filtration rate, renal blood flow, plasma renin activity, plasma aldosterone, free-water clearance or clearance of furosemide with either treatment. We conclude that renal prostaglandins are involved in the control of sodium excretion and urinary volume in patients with congestive heart failure even if renal hemodynamics are unaffected. Sulindac seems to be a selective inhibitor of extrarenal cyclooxygenase and consequently an appropriate drug for patients who require both diuretics and anti-inflammatory therapy.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Clinical pharmacological aspects on nitrate tolerance.

There is strong evidence that nitrate tolerance develops rapidly during repeated administration in the systemic resistance vascular bed and that there exists cross tolerance between different nitrates. There are divergent opinions on how tolerance in the systemic capacitance and the pulmonary vascular bed develops. This may be explained by real differences in tolerance development in ischemic heart disease and congestive heart failure but also by the use of several different preparations of nitrates in the studies performed. Available data on the pharmacokinetics of nitrates present a complex picture with highly variable bioavailability, clearance and apparent volume of distribution both inter- and intraindividually. It is suggested that nitrate tolerance should be studied in very homogeneous groups of patients with well defined hemodynamics. The nitrate used should have a very short half-life allowing for simulation of various modes of administration by intravenous infusion.

Drug Tolerance↗
PubMed1985

Kinetics of intravenous and oral pentoxifylline in healthy subjects.

The kinetics of a sustained-release formulation of pentoxifylline were compared with those of a capsule and an intravenous infusion. Ten healthy subjects received each of the oral pentoxifylline formulations (400 mg) three times a day for 9 days in a random crossover fashion. Pentoxifylline (200 mg) was also given intravenously on a separate day. After intravenous pentoxifylline, plasma levels declined in a biphasic manner, with a terminal t1/2 of 1.63 +/- 0.8 hr. Plasma clearance was 1333 +/- 481 ml/min and the volume of distribution was 168 +/- 82.3 l. Cumulation of pentoxifylline in plasma after repeated dosing was minimal. Plasma levels of the active 5-hydroxylated metabolite were generally higher than those of the parent drug after both routes of administration. Urinary excretion of two acid metabolites after oral and intravenous dosing indicated almost complete absorption of drug-related substances from both of the oral formulations, although bioavailability averaged 20% to 30%.

Administration, Oral↗
PubMed1984

Effects of cardiac failure on the pharmacokinetics of the diuretic tizolemide.

Tizolemide, an alkaline sulphonamide diuretic, was given i.v. in one dose and orally during one week to eight patients with compensated cardiac failure. They had essentially normal glomerular filtration rate but reduced renal plasma flow. Tizolemide was almost completely absorbed from the gastrointestinal tract. The drug was mainly eliminated via tubular secretion. Renal clearance of the drug was much lower than in healthy subjects because of low renal plasma flow. As a consequence plasma half-life was prolonged considerably in some patients. It was concluded that drugs with mainly tubular renal elimination may have a reduced elimination rate in patients with cardiac diseases despite normal glomerular filtration rate.

Administration, Oral↗
PubMed1984

Aspects on pharmacokinetics of some diuretics.

This review summarizes the present knowledge of some commonly used diuretics. Bendroflumethiazide and bumetanide are completely absorbed from the gut while the uptake of hydrochlorothiazide, chlorthalidone and furosemide averages about 65%. The degree of uptake of amiloride and spironolactone is unknown but exceeds 50%. Plasma t 1/2 of bumetanide and furosemide are approximately 1 h. The clinically important phase of the plasma concentration of bendroflumethiazide has a t 1/2 of 3 h, although a slower phase with a t 1/2 of 9 h has been described. Hydrochlorothiazide and amiloride, often used in combination, both have a t 1/2 of about 10 h. Canrenone, an active metabolite of spironolactone, has a t 1/2 of 15-20 h. Chlorthalidone is eliminated very slowly with a t 1/2 of about two days. This is partly caused by an extensive binding to carbonic anhydrase in the erythrocytes. The protein binding of bendroflumethiazide, bumetanide, canrenone and furosemide is approximately 95%. The binding of chlorthalidone and hydrochlorothiazide is about 75 and 40% respectively. All mentioned diuretics except spironolactone are in part eliminated renally, mainly via tubular secretion. This is the major elimination route for amiloride and hydrochlorothiazide, while it constitutes one third to two thirds for bendroflumethiazide, bumetanide and furosemide. Spironolactone is exclusively eliminated as metabolites.

Amiloride↗