Interactions with Lithium

Lithium interacts with other drugs. Neurotoxicity has been reported in association with haloperidol and other antipsychotic drugs, most particularly when both are given in high doses for a prolonged period 

Low doses of /3 blocking agents are used to treat lithium-induced hand tremor (194). Lithium clearance, however, was shown to be diminished in propranolol-treated patients (195). Propranolol thus might better be used in small doses immediately prior to a stressful occasion, rather than coadministered chronically with lithium. 

Of particular importance to lithium patients is a well-documented interaction with nonsteroidal antiinflammatory drugs (NSAIDs). These drugs may increase serum lithium concentrations by as much as 60% because of their effect of reducing renal lithium clearance. The risk of lithium toxicity is of major clinical importance due to the widespread use of NSAIDs by general practitioners who may not be aware of the problem, and even as over-the-counter medicines. Careful monitoring of serum lithium concentrations is essential when these drugs are combined (193). 

Some interactions between lithium and other drugs are beneficial. In approximately 60% of depressed patients in whom conventional treatment has failed, the combination of lithium and antidepressant drugs proves successful where neither drug was effective alone (190, 193, 196, 197). Combinations of lithium and carbamazepine are also increasingly used in the successful treatment of refractory affective illness (198). This combination is generally safe, though the possibility of neurotoxicity should be considered. One additional potential benefit of the use of lithium in this way is the prevention of leukopenia induced by carbamazepine (199). Inosotol phospholipid metabolism is not affected by carbamazepine, suggesting an alternative locus of action from that of lithium (200). 

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These compounds are thermally stable, but sensitive to oxidation. The boron atom is not very reactive, due to conjugation of its vacant orbital with the nitrogen lone electron pair, resulting in the absence of intermolec-ular coordination. However, these compounds undergo reactions with methanol, giving methoxy derivatives (172). The latter interact with lithium alkylides, and form, depending on their nature, borates (173) or 13-alkyl derivatives (174) [Eq. (131)]. 

The use of lithium to isolate the anion current is not feasible for all transporters because lithium cannot support uptake in GLT-1 (59). This raises the interesting question of which residues are responsible for the interaction with lithium (see next section). 

Carbamazepine, interaction with lithium, 36 66 Carbanion mechanism, 36 277-282 Carbenes... 

Diuretics, interaction with lithium, 36 65-66 Divalent cations hydration shell, 34 211 structure, 34 210-212... 

Nonsteroidal antiinflammatory drugs, interaction with lithium, 36 66 No-phonon transition, 35 324 Norbomadiene complexes with cobalt, 12 286 with copper, 12 328, 330, 331 with gold, 12 348, 349 with group VIB metals, 12 231 with group VnB metals, 12 241 with iron, 12 265 with palladium, 12 314 with platinum, 12 319 with rhodium, 12 300-302 with ruthenium, 12 278, 279 with silver, 12 340-342, 344, 346 Norbomylsiloxane, 42 226, 228 Notch receptor proteins, 46 473, 475 h (N)" oxime complexes, osmium, 37 260 h (N,0) oxime complexes, osmium, 37 260 (NPr ljiFeCfrdto),], magnetization versus temperature, 43 230... 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

There are several clinically significant drug interactions with lithium, including the following ... 

Dubovsky SL, Franks RD, Allen S. Verapamil a new antimanic drug with potential interactions with lithium. J Clin Psychiatry 1987 48 371-372. 

Belmaker, R. H. How does lithium work in manic depression Clinical and psychological correlates of the inositol theory. Ann. Rev. Med. 47 (1996) 47-60. Finley, P. R. Clinical relevance of drug interactions with lithium. Clin. 

Depending on quantitative ratio of chemical agents, this reaction may also result with synthesis of chloralanes A1H2C1 or A1HC12. Chloralane interacts with lithium tetrahydroaluminate in ether with formation of aluminum hydride [3] ... 

Drug interactions with lithium have been reviewed (569-573) another review focused on interactions in the elderly (573). A review of drug interactions with lithium considered both pharmacokinetic interactions [for example diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs)] and pharmacodynamic interactions (for example antipsychotic drugs, SSRIs) and summarized the most important ones in tabular form (569). 

Although amiloride may reduce the renal clearance of lithium, it appears to be free of the troublesome interaction with lithium that complicates the use of thiazides and loop diuretics. 

A review of aripiprazole included a brief mention of no apparent pharmacokinetic interaction with lithium (624). 

In one study, there was a mean increase of only 17% in healthy volunteers taking celecoxib 200 mg bd (667). When celecoxib was co-administered with lithium, celecoxib concentrations were higher for the first 6 hours after the dose but the AUC was not altered significantly (668). In another review it was mentioned that clinically significant interactions with lithium (increased lithium concentrations) had been identified, but no detail was presented (669). Both celecoxib and naproxen reduced the renal clearance of lithium (used as a measure of proximal tubular sodium reabsorption) (670). 

Mefenamic acid may have interacted with lithium in a patient with reduced renal function (SEDA-13, 83) (684). 

Unlike other NSAIDs, sulindac supposedly does not interact with lithium (SEDA-10, 82). However, there has been a report of a toxic increase in serum lithium concentration in a 23-year-old man and a 27-year-old woman (to 2.0 and 1.7 mmol/1 respectively) (690). 

Muller-Oerlinghausen B. Drug interactions with lithium. A guide for clinicians. CNS Drugs 1999 11 41-8. 

Finley PR, Warner MD, Peabody CA. Clinical relevance of drug interactions with lithium. Clin Pharmacokinet 1995 29(3) 172-91. 

Methyldopa, carbamazepine, and phenytoin may interact with lithium to increase its toxicity... 

While the isolated allyl anion is calculated to have a planar structure 42), interaction with lithium results in movement of the three of the hydrogens markedly out-of-plane (43-45). The ab initio (3-21G basis set) allyllithium geometry is shown in 25c the central hydrogen is bent toward and the two inner hydrogens at C(l) and C(3) are bent away from the lithium. 

Drug Interactions with Lithium Lithium and the Thyroid Gland Lithium and Bone Microbiological Effects of Lithium Conclusion References... 

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