Renal elimination of lithium in rats with lithium intoxication

The relation between urine flow (V), lithium clearance (CLi) and sodium clearance (CNa) was studied in rats given food containing lithium in amounts leading to inhibition of distal reabsorption of water and sodium. Maximum inhibition of the reabsorption of water was reached at serum lithium concentrations of about 1 mM. At higher serum lithium levels the rats developed intoxication due to a lowering of CLi and a consequent rise of the serum lithium concentration. The intoxication was characterized by a proportional decrease of V and CLi. The decrease of V and CLi was not related to changes of CNa. The results indicate that lithium is reabsorbed in the proximal tubules in parallel with sodium and that the lowering of CLi is due to increased fractional proximal reabsorption of lithium and sodium compensatory to inhibition of the distal reabsorption of sodium.     

Operating experiences with electrolytes containing lithium fluoride

Additions of lithium salts to the cryolite bath of horizontal stud Soederberg cells have been tested for the last 10 years, at first with some pilot cells and then with full potlines of 35 and 40 kamp cells. Under special conditions, economic benefits result. Voltage, power, anode paste, and fluorine electrolyte consumptions are lower; current efficiency is increased. On the other hand, more attention is necessary in pot operations because the alumina solubility is reduced. The addition of a readily soluble alumina is advantageous. The LiF-content in the electrolyte seems to be limited according to type of pot to 2 to 5 pct. Type and method of adding the lithium salts affect the consumption of lithium salts. The influence of supplementary additions, as CaF₂, KF, MgF₂, and NaCl, will be discussed.     

Clinical relevance of drug interactions with lithium

Although lithium continues to be regarded as the treatment of choice for bipolar disorders, the clinical use of this mood stabiliser is associated with an extremely narrow therapeutic range. Relatively minor increases in serum concentrations may induce serious adverse sequelae, and concentrations within the therapeutic range may result in toxic reactions. The safety of combining lithium with other medications, therefore, is a major concern, and extensive clinical experience has served to identify several significant drug interactions. Lithium removal from the body is achieved almost exclusively via renal means. As a result, any medication that alters glomerular filtration rates or affects electrolyte exchange in the nephron may influence the pharmacokinetic disposition of lithium. Concomitant use of diuretics has long been associated with the development of lithium toxicity, but the risk of significant interactions varies with the site of pharmacological action of the diuretic in the renal tubule. Thiazide diuretics have demonstrated the greatest potential to increase lithium concentrations, with a 25 to 40% increase in concentrations often evident after initiation of therapy. Osmotic diuretics and methyl xanthines appear to have the opposite effect on lithium clearance and have been advocated historically as antidotes for lithium toxicity. Loop diuretics and potassium-sparing agents have minor variable effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been associated with lithium toxicity, although the relative interactive potential of specific NSAIDs is difficult to determine. Small prospective studies have demonstrated large interindividual differences in lithium clearance values associated with different NSAIDs. A growing body of evidence also suggests that ACE inhibitors may impair lithium elimination, but further investigations are needed to identify patients at risk. Anecdotal reports have linked numerous medications with the development of neurotoxicity without an apparent effect on the pharmacokinetic disposition of lithium. Antipsychotics, anticonvulsants and calcium antagonists have all be implicated in a sufficient number of case reports to warrant concern. As these medications have all been commonly coadministered with lithium, the relative risk of serious interactions appears to be quite low, but caution is advised.     

Nephrotic syndrome and renal insufficiency associated with lithium therapy

OBJECTIVES: To assess the effects of a single dose of a non-absorbable fat substitute, sucrose polyester, on gastrointestinal function. METHODS: The effects of 50 g of sucrose polyester taken as a single drink on gastric emptying, small bowel transit time (SBTT), whole gut transit time (WGTT) and faecal weight compared with a control fat were examined in double-blind studies. The effect of sucrose polyester on gallbladder ejection fraction and gastrointestinal hormones was also assessed. RESULTS: Sucrose polyester was found to accelerate gastric emptying significantly (98.33 +/- 71.0 vs. 112.92 +/- 82.0 min, P = 0.042) but to slow SBTT (153.75 +/- 36.25 vs. 128.75 +/- 47.39 min. P = 0.006). A trend to faster WGTT (37.47 +/- 15.61 vs. 46.63 +/- 20.65 h) and increased faecal weight was observed (453.33 +/- 122.05 vs. 395.0 +/- 107.85 g/48 h), but this did not reach statistical significance. There was a striking reduction in gallbladder ejection fraction with sucrose polyester (21.69 +/- 25.32 vs. 45.27 +/- 27.67%), P = 0.039) and a corresponding significant decrease in the release of cholecystokinin. Lower levels of motilin and enteroglucagon were also observed. CONCLUSIONS: Sucrose polyester has significant effects on gastrointestinal transit, gallbladder contraction and gastrointestinal hormones. These effects can be explained on the basis of decreased luminal products of digestion and may have implications for the widespread use of sucrose polyester as a fat substitute.     

Sodium and lithium interactions with the Na+/Dicarboxylate cotransporter

The two-electrode voltage clamp was used to study the currents associated with transport of succinate by the cloned Na+/dicarboxylate cotransporter, NaDC-1, expressed in Xenopus oocytes. The presence of succinate induced inward currents which were dependent on the concentrations of succinate and sodium, and on the membrane potential. At -50 mV, the K0.5succinate was 180 microM and the K0.5Na+ was 19 mM. The Hill coefficient was 2.3, which is consistent with a transport stoichiometry of 3 Na+:1 divalent anion substrate. Currents were induced in NaDC-1 by a range of di- and tricarboxylates, including citrate, methylsuccinate, fumarate, and tricarballylate. Although Na+ is the preferred cation, Li+ was also able to support transport. The K0.5succinate was approximately 10-fold higher in Li+ compared with Na+. In the presence of Na+, however, Li+ was a potent inhibitor of transport. Millimolar concentrations of Li+ resulted in decreases in apparent succinate affinity and in the Imaxsuccinate. Furthermore, lithium inhibition under saturating sodium concentrations showed hyperbolic kinetics, suggesting that one of the three cation binding sites in NaDC-1 has a higher affinity for Li+ than Na+. We conclude that NaDC-1 is an electrogenic anion transporter that accepts either Na+ or Li+ as coupling cations. However, NaDC-1 contains a single high affinity binding site for Li+ that, when occupied, results in transport inhibition, which may account for its potent inhibitory effects on renal dicarboxylate transport.     

Heart pacemaker with lithium batteries. 2 years' clinical experience

102 lithium-powered cardiac pacemakers manufactured by Cardiac Pacemakers Inc. (CPI 301 UD, 101 UA and 501 UD) were implanted in 94 patients. During the observation time (25 months) the following complications were registered: 2 pulse generator failures, 4 failures of the demand-function, anodic muscle-twitching in 2 patients, 2 erosions of the pacemaker-pocket and 1 hematoma of the pocket. 5 pulse generators were exchanged without malfunction of the pacemaker. In 4 patients reinterventions on the electrode had, to be performed. 4 deaths occurred, none of them related to malfunction of the pacemaker. 2 lithium-powered pacemakers were explanted in other hospitals, for reasons not known to us and 1 patient left the German Federal Republic. 83 patients are under control with well working lithium-powered pacemakers.     

Phototherapy and lithium prophylaxis

A random sample of patients (n = 43) had been investigated to detect any difference in response of bright light therapy in lithium-treated inpatients (n = 18) suffering from depression. Only 27% of the lithium-based inpatients respond to bright light therapy, but 73% of patients respond who were not treated with lithium. We conclude that lithium therapy reduces the chance of achieving t remission of depression by bright light therapy.     

Warned reaction times of manic-depressive patients with and without lithium.

To assess the performance of manic-depressive patients and normal controls, a warned reaction time task was employed with 20 normal control Ss and 36 manic-depressive outpatients in the free, hypomanic, and depressed states, with and without maintenance levels of lithium carbonate. A warning light appeared at a variable interval preceding a light to which the S responded with a keypress. All Ss received both a regular and an irregular series with warning intervals of 1, 2, 4, 8, and 16 sec. In the regular series, blocks of intervals followed every other interval equally often. Manic-depressives were uniformly slower than controls in both series at all intervals. Maintenance levels of lithium facilitated reaction times particularly at the longer intervals in the irregular series. Depressive as well as hypomanic states tended to yield faster reaction times than the free state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Labial herpes in patients with affective disorders receiving long-term lithium carbonate

Lithium carbonate has been administered to 69 patients (45 women and 24 men) for 1-17 years as affective disorders prevention. Its effect on the recurrence and clinical course of labial herpes infection has been analysed both prior to and after the administration of lithium carbonate. Labial herpes has been diagnosed in 28 patients before lithium prophylaxis. The drug significantly decreased virus infection recurrence incidence in this group. No labial herpes recurrence has been noted in 13 patients after the treatment. Lithium efficiency has not been dependent on patients' age, duration of therapy, and lithium levels in both blood serum and erythrocytes. These results suggest, that lithium salts may be effective in certain herpes simplex infections at doses used for prevention affective disorders.     

Memory performances in depressed patients during prophylactic treatment with lithium salts

The study involved 42 subjects suffering from unipolar depression (35 females and 7 males) who had received 600-1,200 mg of lithium carbonate daily for periods ranging from 6 months to 7 years. Concurrently with the memory tests, the patients were also submitted to the Hamilton test for the evaluation of depression and blood samples were taken in order to measure lithium blood levels. In the groups of subjects examined by us (grouped according to lithemia, time on the drug and degree of depression, as, evaluated by Hamilton's test), significant differences were found only in the short-term figure test and, partially, in the long term memory verbal test.