30 Õrig mand I lithiumbehandling fÕr adderet haloperidol og nifedipin og udvikler ataxi, dysartri og tremor. Herefter seponeres haloperidol men symptomerne forsvinder f°rst efter seponering ad nifedipin. Forfatterne merner ogsÕ at lithiumudskillelsen falder da serum lithium stiger.

The calcium channel blockers are a group of drugs that have recently become available for the treatment of angina. They act by blocking the entry of calcium into cells during depolarization. Lithium has electrochemical qualities similar to calcium and influences calcium metabolism and calcium transport. The case reported here documents the use of diltiazem in a patient treated with lithium. A possible synergistic drug interaction occurring between diltiazem and lithium is reported

To evaluate the renal tubular effects of felodipine in a low (1.25-mg) and a high (10-mg) dose, lithium clearance was measured and related to renal hemodynamics in 10 healthy volunteers. After felodipine (1.25 mg), mean blood pressure decreased 4 mm Hg and heart rate increased 4 beats per minute. GFR and renal hemodynamics were unaltered. Natriuresis and diuresis increased and lithium clearance and fractional excretion of lithium were unchanged as compared with placebo. Felodipine (10 mg) decreased mean blood pressure 8 mm Hg; heart rate increased 16 beats per minute, and plasma catecholamines were elevated. GFR was unaltered, whereas RBF increased and renal vascular resistance decreased. Natriuresis and diuresis were further increased, and lithium clearance and fractional excretion of lithium were elevated. In conclusion, felodipine in a low dose of 1.25 mg, which did not change renal hemodynamics, had natriuretic and diuretic effects at a predominantly postproximal tubular site, whereas a high dose of 10 mg, which increased RBF and decreased renal vascular resistance, had additional natriuretic and diuretic effects in the proximal tubule

The interaction of calcium antagonists, including the dihydropyridine calcium antagonists (e.g. nifedipine), verapamil and diltiazem, with drugs from other classes has major clinical ramifications as the use of drug combinations increases in frequency. Combinations are used in the treatment of disorders ranging from hypertension to cardiac rhythm disturbances, angina pectoris and peripheral vasospastic disease. In this era of organ transplantation, drugs like cyclosporin are coming into potential conflict with an ever-growing list of drugs. Drug combinations used as part of long term therapies are also making their appearance in toxic drug reactions, including antituberculous and anticonvulsant agents. Bronchodilators and H2-blockers also fall into this category of potential culprits of combined drug toxicity, and the interactions of calcium antagonists with beta-blockers and antiarrhythmic agents are also becoming a matter of concern

The drug-drug interactions discussed in this article have either documented or suspected clinical relevance for patients with cardiovascular disease and the clinician involved in the care of these patients. Oftentimes, drug-drug interactions are difficult, if not impossible, to predict because of the high degree of interpatient variability in drug disposition. Certain drug-drug interactions, however, may be avoided through knowledge and sound clinical judgment. Every clinician should maintain a working knowledge of reported drug-drug interactions and an understanding of basic pharmacokinetic and pharmacodynamic principles to help predict and minimize the incidence and severity of drug-drug interactions.

Choreoathetose udviklet under kombinationsterapi tolket som farmakodynamisk interaktion.

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

1. The benefit of a combined treatment with the calcium antagonist nimodipine and lithium in a bipolar I disorder (currently manic, DSM IV 296.44, ICD 10 F 31.1) was explored and documented in a longitudinal single case study. 2. Nimodipine (270 mg/d) was added to lithium (900 mg/d), substituting for previously administered neuroleptics, in an up to then unsatisfactorily treated manic patient. 3. A clear-cut improvement in the patient´s condition was achieved within a fortnight, and lasted over the continuation period of this drug regimen. This combined treatment was discontinued after eight weeks and lithium alone was then administered. Within three months another manic episode appeared. 4. Side-effects and changes of lithium blood levels were not observed during the combined treatment with nimodipine and lithium. 5. Further research on the benefits of adding a calcium antagonist, instead of neuroleptics, to lithium therapy for bipolar manic disorder patients who do not respond sufficiently to lithium is recommended. In addition, the benefits of a long term prophylaxis of nimodipine alone or in combination with lithium should be evaluated in those bipolar patients who still show a high relapse frequency on lithium alone

Calcium channel blockers are being used increasingly for a variety of cardiovascular problems. Diltiazem hydrochloride, a benzothiazepine derivative, has been reported to have a low incidence of adverse side effects. We report a case of acute psychosis associated with the use of diltiazem in a patient receiving lithium carbonate therapy. Both diltiazem hydrochloride and lithium carbonate have calcium antagonist effects in the central nervous system, and we review their mechanisms of action. A possible synergistic drug interaction between diltiazem and lithium is reported

Kommenterer pÕstÕet interaktionstilfµlde mellem lithium og dilthiazem, som beskrevet af [3024].

1. We have studied the diuretic and natriuretic effects and the tubular site of action of nifedipine using free water clearance (CH2O) and lithium clearance. 2. We have compared the effects of nifedipine (10 mg p.o.) with those of placebo and of frusemide (40 mg p.o.) in seven healthy volunteers during maximal water diuresis. 3. Compared with placebo, nifedipine caused a significant rise in urinary flow rate and CH2O, paralleled by significant increases in fractional excretion of sodium and lithium. The rise in sodium excretion was not accompanied by an increase in potassium excretion. 4. Frusemide caused increases in sodium and lithium excretion, comparable with the effects seen after nifedipine. CH2O did not change however. 5. Our study demonstrates that nifedipine has a clear diuretic and natriuretic effect in healthy volunteers, which is predominantly established by interference with proximal tubular sodium reabsorption. Lithium clearance did not allow us to differentiate between nifedipine and frusemide effects, thus questioning the reliability of lithium as a marker of proximal tubular sodium reabsorption

The increasing use of the calcium-entry blockers has led to an enhanced potential for drug interactions with a variety of different drugs. Interactions with cardiovascular agents are of great concern because of the consequences of synergistic negative dromotropism or inotropism. We therefore assessed the concomitant use of calcium-entry blockers and cardiac glycosides, beta-blockers, antiarrhythmic agents, and other chemical types of calcium-entry blockers from a standpoint of clinical relevance. We also evaluated reported drug interactions with H2-receptor antagonists, anticonvulsants, lithium carbonate, general anesthetics, cytostatic drugs, rifampin, and sulfinpyrazone with regard to clinical implications, along with the modification of calcium-entry blocker dose for concurrent social drug use, such as cigarette smoking and ethanol intake. Although a myriad of potential drug interactions exists for these agents, combination therapy is still a reasonable alternative if doses are adjusted appropriately

Case med neurotkcisitet ved kombinationen lithium og verapamil. Blev geudl°st ved provokationsfors°g.

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments

74 Õrig kvinde I behandling med lithium I terapeutisk niveau fik adderet verapamil og udviklede efter to uger neurotoksiske symptomer (gangbesvµr, tremor, nausea mm).

42-Õrig kvinde I lithium-behandling fik adderet verapamil og udviklede efter en uge neurotoksiske symptomer soma taxi og tinnitus og ogsÕ nausea. Svandt efeter seponering og kom igen efter reeksposition.

Verapamil is a calcium channel blocking agent with possible antimanic properties. In two elderly manic patients taking the medication in combination with lithium carbonate, profound bradycardia developed and was followed by a fatal myocardial infarction in one case. Clinical implications and possible mechanisms of cardiovascular interactions between verapamil and lithium are discussed. Caution is advised in the use of lithium and verapamil together.