Owing to its renal excretion, lithium has renally mediated rather than hepatically mediated drug-drug interactions. Lithium excretion is decreased by medications such as thiazides, non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and, to a lesser extent, frusemide (furosemide), and by physiological states such as dehydration, advanced age, and renal disease (T.§ble...,3.).(66) Owing to lithium's poor therapeutic index, these interactions can result in clinical lithium toxicity, unless a dosage adjustment is made. In contrast, lithium clearance is less consistently affected by amiloride, acetylsalicylic acid, and sulindac, and increased with other medcations with diuretic effects such as acetazolamide, mannitol, aminophylline, caffeine, and theophylline, as well as during pregnancy. Increases in lithium clearance may yield clinical inefficacy if plasma lithium concentrations fall below the therapeutic range.
Table 3 Summary of the most important drug interactions with lithium salts
Different calcium-channel blockers differentially affect carbamazepine levels: while verapamil and diltiazem increase carbamazepine levels substantially, potentially causing toxicity, this is not the case with nimodipine, isradipine, or amlodipine. Preliminary data from our group and others suggest that carbamazepine decreases nimodipine levels after a 60-mg challenge dose. In our study, group mean peak nimodipine levels during treatment with carbamazepine were about one-half of those observed during treatment with nimodipine alone, although this finding showed only a trend level of significance probably due to small sample size.
When calcium-channel blockers are added to b-adrenergic blocking agents, depression of ventricular function, cardiac slowing, and atrioventricular block can result.6.' Combining calcium-channel blockers with a-adrenergic blocking agents may produce hypotension. 6.> Verapamil and nitrendipine increase plasma concentrations of digoxin and produce bradycardia, hypotension, or atrioventricular block. (7 I1* Tabled (64 illustrates several other interactions between calcium-channel blockers and other drugs used to treat mania.(69,7,7,7575,7,7,78,79 and 80)
Table 4 Some calcium-channel blocker interactions
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