Lithium cardiac effects

Reversible electrocardiographic (EKG) T-wave depression occurs frequently with therapeutic serum lithium concentrations. Arrhythmias have occurred rarely. The cardiac effects of lithium may result partly from displacement of potassium from intracellular myocardial sites by lithium, resulting in a slow, partial depletion of intracellular potassium (Kawata, 1979). 

Mitchell JE, Mackenzie TB. Cardiac effects of lithium therapy in man a review. J Clin Psychiatry 1982 43 47-51. 

Two reviews of the cardiac effects of psychotropic drugs briefly mentioned lithium and dysrhythmias, with a focus on sinus node dysfunction (122,123), reports of which, as manifested by bradycardia, sinoatrial block, and sinus arrest, continue to accumulate in association with both toxic (124) and therapeutic (125,126) serum lithium concentrations. The rhythm disturbance normalized in some cases when lithium was stopped (124,126), persisted despite discontinuation... 

Cases of lithium toxicity, its cardiac effects, and issues of cardiac dysfunction in children have been reviewed in the light of a cardiac dysrhythmia in a child. 

Lithium may cause cardiac effects including T-wave flattening or inversion (up to 30% of patients), atrioventricular block, and bradycardia. If a patient has preexisting cardiac disease, a cardiologist should be consulted and an electrocardiogram obtained at baseline and regularly during therapy. 

Cardiovascniar Lithium generally does not have significant cardiac effects. However, lithium toxicity has been associated with transient electrocardiographic changes. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

No significant interactions have been reported when tiie expectorants are used as directed. The exception is iodine products. Lithium and other antithyroid drug may potentiate the hypotliyroid effects of these drug if used concurrently with iodine products. When potassium-containing medications and potassium-sparing diuretics are administered with iodine products, the patient may experience hypokalemia, cardiac arrhythmias, or cardiac arrest. Thyroid function tests may also be altered by iodine... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Lithium should not be administered to patients with fluctuating or unstable renal function. Because hthium may affect functioning of the cardiac sinus node, patients with sinus node dysfunction (e.g., sick sinus syndrome) should not receive hthium. Although hthium also has acute and chronic effects on the thyroid, patients with hypothyroidism may receive hthium if the thyroid disease is adequately treated and monitored. Laboratory tests that should be performed before initiation of hthium are listed in Table 5-1. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

The issue of lithium-induced dysmorphogenesis is not settled. An earlier report suggested an increase in cardiac anomalies—especially Ebstein s anomaly —in lithium babies, and it is listed as such in Table 59-1 in this book. However, more recent data suggest that lithium carries a relatively low risk of teratogenic effects. Further research is needed in this important area. 

Lithium + antiarrhythmic drugs —> potentiation of the cardiac conduction effects of the antiarrhythmic drugs. 

A very uncommon adverse effect involves sinus node dysfunction (extreme bradycardia, sinus arrest, sinoatrial block), which can be associated with syncopal episodes, perhaps due to hypothyroidism (119,120). In such cases, lithium must either be withdrawn or continued in the presence of a pacemaker. At therapeutic concentrations, other cardiac conduction disturbances have been reported, sometimes in conjunction with hypercalcemia (121), but are uncommon. 

To determine the safety of using lithium chloride dilution to measure cardiac output, the pharmacokinetic and toxic effects of intravenous lithium chloride have been studied in six conscious healthy Standardbred horses (527). The mean peak serum concentration was 0.56 mmol/1. There were neither toxic effects nor significant changes in laboratory studies, electrocardiograms, or gastrointestinal motility. Three horses had increased urine output. 

A similar study was performed in patients undergoing cardiac surgery and healthy volunteers the highest dose of lithium chloride was 0.6 mmol given intravenously five times at 2-minute intervals (528). Unfortunately, no mention was made of tolerability or adverse effects. 

Neuroleptic drugs are often used in mood stabilizer combinations. However, there have been few controlled studies of the use of such combinations, and interactions are potentially dangerous. The advantages and disadvantages of all currently used mood stabilizer combinations have been extensively reviewed (641). Some effects are well known neurotoxicity, hypotension, somnambulistic-like events, and cardiac and respiratory arrest associated with the combination of lithium and traditional neuroleptic drugs considered as a first-line treatment for classic euphoric mania with psychotic features. 

Because of the potential effect it may have on other body systems and the risk of toxicity, a baseline medical workup is de rigueur in every patient who is a candidate for lithium therapy. This workup includes laboratory tests aimed at evaluating kidney function, thyroid status, complete blood count, cardiac function, and so on. 

In addition to drugs used for their antithyroid effects, the following substances can cause hypo-th3rroidism lithium (for mania/depression), amio-darone (cardiac antiarrhythmic), PAS (for tuberculosis), phenylbutazone (antirheumatic), iodide (see above), cobalt salts (for anaemia), resorcinol (for leg ulcers). Effects are generally reversible on withdrawal. 

Group la Lithium - Lithium salts were used indiscriminately over the early part of this century for treatment of gout, epilepsy. Insomnia, hypertension and as salt substitutes in cardiac disease. Unfortunately, toxicity associated with lithium salt therapy was not known at that time. Many cases of serious side effects and deaths resulted which led to their disuse. In recent years judicious use of lithium salts, primarily lithium carbonate, for the control of manic symptoms has reestablished their utility in clinical practice. 

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