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At least 19 recordsLinked to original sources

PubMed1979

Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate.

A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.

Animals↗

PubMed1979

The effect of water deprivation on lithium clearance and lithium excretion fraction in lithium-polyuric rats.

The effect of water deprivation on lithium clearance was studied in rats with lithium-induced polyuria. During a 3-hr period of water deprivation, the rats lost water in amounts corresponding to about 10% of body weight. Lithium clearance fell to about 25% of the level observed in rats which were not water deprived. During shorter periods of water deprivation, the fall of lithium clearance was less. The decrease of lithium clearance was partly due to a fall of inulin clearance and partly due to a fall of fractional excretion of lithium. The decrease of the two variables contributed to the same extent to the decrease of lithium clearance. The findings support the suggestion that insufficient intake of water in patients with lithium-induced polyuria may lead to a rapid lowering of lithium clearance and, hence, to a rise of the serum lithium concentration and development of intoxication.

Animals↗

PubMed1977

Comparison of plasma lithium levels and their interindividual variations with coated lithium carbonate tablets and a medium-slow-release lithium sulphate preparation (Lithionit Duretter).

In a cross-over study in 10 subjects, rapidly dissolving coated lithium carbonate tablets and medium-slow-release lithium sulphate tablets were compared. Both preparations were administered twice a day. They gave similar post-absorptive concentrations of lithium in plasma and similar standard deviations of these concentrations. The medium-slow-release tablets gave smaller increases of lithium in plasma, and postponed the absorption peaks. They also gave less interindividual variation of lithium in plasma during the first few hours after administration.

Adult↗

PubMed1975

[Mechanism of action and kinetics of lithium. I. Biochemical and experimental pharmacological findings after administration of lithium-conclusions on the mechanism of the therapeutic effect of lithium].

A comprehensive consideration of biochemical and pharmacodynamic lithium (Li) effects enabled an explanation of the Li mechanism (Fig 1). According to this concept, Li might possibly affect the activity of membrane-bound ATPases in dependence on the initial situation, dose and duration of application. Research into Li-kinetics suggested the participation of active process in the transport of the ion through the organism. Li-kinetics describes distribution within a multiple-compartment system and, with the exception of the resorption phase, its independent of the anion used. The elimination (half-life time 22 to 25 hrs) is limited by backward flow form the tissue.

Adenosine Triphosphatases↗

PubMed1978

Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate.

Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.

Animals↗

PubMed1979

Syncope caused by lithium treatment. Report on two cases and a prospective investigation of the prevalence of lithium-induced sinus node dysfunction.

Lithium salts have been widely used for several years in the treatment of manic-depressive psychosis. Various side-effects of lithium salts have been described. The present case report present two patients in whom sinus node dysfunction leading to syncope was caused by lithium. One of the cases showed signs of depressed sinus node function even when not on lithium, but no symptoms arose until lithium treatment was commenced. The second case showed no signs of depressed sinus node function when lithium was withdrawn. To study the prevalence of sinus node dysfunction in patients on lithium therapy, 97 consecutive patients on lithium were examined. The examination included case history, ECG and carotid massage. In two patients lithium could not be ruled out as being responsible for sinus node depression and in one patient the same was true for the atrioventricular node. None of these patients had any symptoms. It is concluded that lithium treatment may result in sinus node dysfunction. This side-effect is, however, not common. Lithium treatment can obviously be instituted in all patients without a history suggesting sinus node dysfunction. Patients with a history of dizziness and/or syncope should not be given lithium until thorough cardiological examination has been carried out. Likewise, a cardiological examination should be performed if patients on lithium develop symptoms of this type.

Aged↗

PubMed1979

The relationship of the lithium erythrocyte: plasma ratio to plasma lithium level.

The relationship of the lithium erythrocyte:plasma ratio to plasma lithium concentration was reviewed in inpatients and outpatients with affective disorders. For some patients, there was a linear correlation between the erythrocyte lithium:plasma lithium ratio and the plasma lithium concentration. For these patients a graph of the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data formed a line that was not significantly different from the data of Lee et al. (1975). Significant correlations were found between the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data and the magnitude of active lithium efflux (Ko) from the erythrocyte. Our data confirm the finding of Lee et al. (1975) that the lithium erythrocyte:plasma ratio is dependent on the plasma lithium concentration. We relate this finding to lithium efflux from the erythrocyte.

Adult↗

PubMed1979

The erythrocyte lithium-plasma lithium ratio in patients with primary affective disorder.

Increasing attention has been given to the significance of intra-cellular concentrations of the lithium ion in patients treated with this drug. The erythrocyte has been the most common cell investigated because of its accessibility and certain similarities between the ion transport mechanisms of this cell and the neuron. Intraerythrocyte lithium is expressed as the ratio of lithium in the cell to the plasma lithium concentration (lithium ratio). The lithium ratio has been reported to be related to a number of clinical variables, including treatment response, clinical state, side-effects, toxicity, diagnosis, and electrophysiological effects. We have investigated the lithium ratio in a large series of patients with a primary affective disorder and in a smaller control group. We found a significantly higher mean lithium ratio in the bipolar diagnostic group than in the unipolar and control groups. There was a trend, not statistically significant, in the unipolar and bipolar groups for females to have higher lithium ratios than males. While not diagnostic, the lithium ratio appears to be another biological variable where bipolar patients, as a group, differ from normals and others with an affective disorder.

Bipolar Disorder↗

PubMed1978

Lithium effects on rat brain glucose metabolism in long-term lithium-treated rats studied in vivo.

The time course of lithium effects on several brain energy metabolites has been investigated in rats. The rats were injected once daily with lithium chloride and killed by freezing in liquid nitrogen 1--8 h after the last injection. The effect of lithium was most marked in the period in which the brain lithium concentration was increasing, whereas the effect was wearing off when the brain lithium concentration had stabilized, even though the lithium concentration was higher. These results led to the hypothesis that the effect of lithium on several parameters depends on the increase in lithium concentration following the administration of lithium, rather than on the absolute concentration of lithium.

Animals↗

PubMed1976

Effect of lithium on cardiovascular performance: report on extended ambulatory monitoring and exercise testing before and during lithium therapy.

To assess the effect of long-term lithium therapy on cardiac arrhythmias and cardiovascular performance, extended ambulatory electrocardiographic monitoring was performed in 12 patients, and rest and exercise electrocardiograms in 10 of 12, before and during lithium therapy. Lithium increased the frequency of premature ventricular contractions in three patients, decreased it in one, and produced no change in eight. Three of four patients with atrial arrhythmias showed improvement during lithium therapy. Exercise performance was unchanged. Although 7 of the 12 patients manifested T wave flattening in the resting electrocardiogram, none had S-T segment displacement at rest or on treadmill exercise. Before lithium therapy, arrhythmias on exercise included premature atrial contractions in four patients, ventricular arrhythmias in four (premature ventricular contractions in four, with couplets in two and with ventricular tachycardia in one). During lithium therapy, exercise did not provoke premature atrial contractions or ventricular tachycardia in any of the patients, but three patients had premature ventricular contractions (with couplets in one case). We conclude that lithium at therapeutic levels may precipitate or aggravate ventricular arrhythmias. When administered to patients with heart disease, factors that interfere with renal clearance of lithium (heart failure, salt restriction, long-term diuretic therapy) must be recognized and doses must be adjusted accordingly. Careful follow-up and electrocardiographic monitoring are advisable if lithium is to be used in the presence of ventricular arrhythmias. Cardiovascular performance as assessed by treadmill exercise testing was not affected by long-term lithium therapy.

Adult↗

PubMed1977

Serum concentrations of lithium after three proprietary preparations of lithium carbonate (Priadel, Phasal and Camcolit).

1 The serum lithium concentration was measured before dosing, and at 2, 4, 6, 8, 10, 20, 22, and 24 h after three proprietary preparations of lithium carbonate (Camcolit, Phasal or Priadel). 2 A total of twenty-eight studies were performed on eleven patients. In seven studies the patients received Camcolit, in ten studies patients received Priadel and in eleven the patients took Phasal. 3 The dose of each preparation was adjusted during a 10 week run-in period to maintain the serum lithium within the normal therapeutic range (0.6-1.2 mmol/1). Five patients received one lithium preparation, one patient received three lithium preparations and five patients received four lithium preparations consecutively. 4 After a single daily dose of Phasal and Priadel, the serum lithium remained within the therapeutic range for 24 h. 5 After a single daily dose of Camcolit, the serum lithium remained within the therapeutic range for only 12 h. 6 After three doses of Camcolit (given at 0.800 h, 12.00 h, and 18.00 h) each day, the serum lithium was maintained in the therapeutic range for 24 h.

Delayed-Action Preparations↗

PubMed1977

Lithium absorption, distribution and clearance and body temperature in rats given lithium plus haloperidol.

Renal lithium clearance, tissue lithium levels, serum lithium concentration, and body temperature were determined in rats given lithium alone or combined with haloperidol (0.5-1 mg/kg). A slight increase in serum lithium concentration occurred in one of the three groups given lithium plus haloperidol. Haloperidol failed to affect renal lithium clearance, tissue lithium levels and body temperature. The data do not support the hypothesis that haloperidol exerts an action on lithium pharmacokinetics.

Animals↗

PubMed1979

Comparison between saliva and serum lithium concentrations in patients treated with lithium carbonate.

The relation between serum and saliva lithium concentration was studied in patients treated with lithium carbonate. In 23 patients a highly variable saliva/serum ratio was found in simultaneous saliva and serum samples. In five patients studied during a period of 4-8 weeks three patients showed a high fluctuation in saliva/serum lithium ratio. In 20 patients saliva lithium concentrations varied unexpectedly in a second sample produced after 15 min. Although some authors report a high and stable relation between saliva and serum lithium concentration, we consider the saliva lithium level unreliable as a prediction of the serum lithium level in patients treated with lithium carbonate.

Carbonates↗

PubMed1977

Adjustment of lithium dose during lithium-chlorothiazide therapy.

There has been a long-held belief that lithium salts cannot be used in the presence of thiazide diuretics. Recently, however, thiazides have been demonstrated to be not only safe, but actually indicated in two situations in which lithium salts are used. The first is in the treatment of lithium-induced nephrogenic diabetes insipidus and the second is in severe manic depressive illness in which high doses of lithium do not produce therapeutic serum or intraeythrocytic lithium concentrations. This new information now makes it possible for some manic depressive patients with serious medical illnesses (such as hypertension or congestive heart failure), in whom thiazide diuretics are routinely used, to be treated cautiously with lithium carbonate. This paper analyzes data from 13 patients taking lithium carbonate and varying doses of chlorothiazide in order to indicate the approximate magnitude of downward adjustment of daily lithium dose which the clinician must make to safely give 500, 750, and 1,000 mg/day of chlorothiazide.

Chlorothiazide↗

PubMed1977

Repression of a lithium pump as a consequence of lithium ingestion by manic-depressive subjects.

The lithium pump in human erythrocyte membranes, which is responsible for extrusion of lithium against a concentration gradient, has been found to be reversibly repressed during periods of lithium carbonate administration. The pump activity of patients prior to lithium therapy is not different from controls. The onset of repression may require several days to several weeks and occurs at specific individual threshold levels of lithium carbonate dosage. Reactivation of the lithium pump occurs sometime after the dosage is discontinued. We postulate that repression of the lithium pump results from systemically available factors which alter membrane structure, and suggest that is such changes also occur in the central nervous system, they may provide insight into one means by which lithium produces its psychotropic affects.

Adult↗

PubMed1978

Lithium concentrations in saliva, plasma and red blood cells of patients given lithium acetate.

Lithium concentrations in saliva, plasma and red blood cells were measured in: 1) six hospitalized patients under long-term lithium therapy, at 2, 5, 9 and 24 hours after oral doses of 24 mEq Li acetate and 2 or 12 hours after 8 mEq Li acetate; and 2) 10 outpatients under chronic lithium treatment at two occasions 8 days apart. With changing plasma concentrations, [Li] saliva varied without any notable time lag. [Li] saliva was always much higher than [Li] plasma. The ratio [Li] saliva/ [Li] plasma water averaged 3.2 +/- 0.2 in 62 determinations, but varied widely at different times after oral lithium in the same individuals and less widely between different individuals. "Prediction" of plasma lithium concentration from measured [Li] saliva appears hazardous, and may provide reliable indications only if [Li] saliva is measured repeatedly. Salivary lithium concentrations were not correlated with either potassium or sodium concentrations. Lithium concentrations in red blood cells were always lower than in plasma: [Li] red blood cell water/ [Li] plasma water averaged 0.37 +/- 0.03. With changing plasma concentrations, rise and fall of red blood cell lithium lagged considerably behind plasma changes. This resulted in a rise of the red blood cell/plasma concentration ratio from a very low value 2 hours after an oral dose to a rather high value 24 hours after an oral dose.

Administration, Oral↗

PubMed1977

The renal handling of lithium: relation between lithium clearance, sodium clearance and urine flow in rats with diabetes insipidus.

In order to study the renal handling of lithium, I examined the relation between the lithium clearance and the urine flow in rats which had hereditary lack of vasopressin production and which had been given a test dose of lithium. The two variables were altered by varying the sodium intake. Rats with a low, medium and high sodium intake had a mean lithium clearance of 0.04, 0.22, and 0.40 ml/min./100 g body weight, respectively. When the sodium intake was increased from a medium to a high level, the lithium clearance and the urine flow rose in proportion to each other (r=0.90). When the sodium intake was decreased from a medium to a low level, the lithium clearance fell relatively more than the urine flow so that the proportion between the two was changed. The experiments show that when vasopressin-induced alterations of the urine flow are excluded and when the sodium intake is not extremely low, proportionality may occur between the lithium clearance and the urine flow. This suggests that the lithium clearance varies in proportion to and is determined by the delivery of sodium from the proximal tubules.

Animals↗

PubMed1976

Locomotor activity and plasma, red blood cell and cerebral cortex lithium concentration in inbred mice given lithium carbonate.

Inbred male C57 BALB, C3H and DBA mice received lithium carbonate in their food for 3 weeks. Their locomotor activity was measured by photocells and the concentration of lithium in their plasma, red blood cells and cerebral cortex was determined. The susceptibility of the inbred strains of mice to the activity-suppressant effect of lithium was C3H greater than DBA greater than BALB = C57. The concentration of lithium in plasma varied between 0.85-1.02 mEq 1. No relationship was found between lithium's pharmacokinetics and its effects on activity. The findings are consistent with the notion that genetic factors can influence the effects of lithium on behavior, but they do not support the hypothesis that genetic determination of lithium's uptake into cells is responsible for these effects.

Animals↗