Lithium monitoring therapy with

Monitoring therapy One of the predictors of lithium clearance, and consequently lithium toxicity, is creatinine clearance [89 ], and lithium concentrations are closely associated with its adverse effects. In a study of 186 patients who were followed between 1973 and 2000 (an average of 5.7 years/patient) in which nine specific adverse effects were recorded monthly in a standardized manner (diarrhea, nausea, vomiting, stomach ache, tiredness, concentration deficits, tremor, polyuria, and polydipsia), the frequency of adverse effects increased as a function of lithium concentration as did their intensity [90. The mean number of adverse effects increased from 3.3 at a concentration of 0.6 mmol/1 to 3.8 in patients with a concentration of 1.2 mmol/1. However, there was also a relation between mood state and adverse effects. Patients with manic symptoms had fewer adverse effects (an average of 2.0),... 

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

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. 

Mania can occur in any age group. Acute manic episodes in the elderly may best be managed with high potency neuroleptics. The use of lithium is not contraindicated in the elderly provided renal clearance is reasonably normal. The dose administered should be carefully monitored, as the half-life of the drug is increased in the elderly to 36-48 hours in comparison to about 24 hours in the young adult. The serum lithium concentration in the elderly should be maintained at about 0.5 mEq/litre. It is essential to ensure that the elderly patient is not on a salt-restricted diet before starting lithium therapy. The side effects and toxicity of lithium have been discussed in detail elsewhere (see p. 198 et seq.), and, apart from an increase in the frequency of confusional states in the elderly patient, the same adverse effects can be expected as in the younger patient. 

Some data have suggested that cisplatin-containing chemotherapy can alter lithium clearance through impaired renal function, and lithium therapy should be closely monitored during treatment with cisplatin-containing regimens (723). 

More recently, newer medicines have been used to treat bipolar manic depression disorder. Carbamazepine and valproate are two anticonvulsants that have been particularly useful with patients who do not respond to lithium. These medications also have to be monitored for proper dosages. Antidepressants may be necessary during severe depressive episodes but may push a patient into the manic state. In severe cases, hospitalization and even electroconvulsive therapy (ECT) may be necessary. 

Psychotic patients are most often treated with clozapine, haloperidol, lithium, olanzapine, or one of the phenothi-azines, or a combination of these drugs. Because response to these drugs is unpredictable and patients are difficult to control, monitoring serum concentration may aid in adjusting therapy. Numerous methods to measure the serum concentration of the various neuroleptic agents have been reported. ... 

A. Pharmacokinetics Lithium is absorbed rapidly and completely from the gut. The dmg is distributed throughout the body water and excreted by the kidneys with a half-life of about 20 hours. Plasma levels should be monitored, especially during the first weeks of therapy, to establish an effective and safe dosage regimen. The therapeutic plasma concentration is 0.6-1.4 meq/L. Plasma levels of the drag may be altered by changes in body water. Thus, dehydration or treatment with diuretics (thiazides), may result in an increase of lithium in the blood to toxic levels. Theophylline increases the renal clearance of lithium. 

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