Lithium monitoring therapy

Toxicity is closely related to serum lithium levels and can occur at therapeutic doses. Facilities for serum lithium determinations are required to monitor therapy. 

Lithium and Diuretics. Sodium depletion is known to increase lithium toxicity, and it is generally recommended that lithium not be used in patients on diuretic therapy or on a sodium-restricted diet. Even protracted sweating or diarrhea can cause sufficient depletion of sodium to result in decreased lithium tolerance. The sodium depletion caused by diuretics reduces the renal clearance and increases the activity of lithium. However, if preferable therapeutic alternatives are not available, concurrent therapy need not be contraindicated as long as the interaction is recognized and appropriate steps are taken to monitor therapy and adjust the dosage. 

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),... 

Lithium fluoride is an essential component of the fluorine cell electrolyte 1% LiF in the KF 2HF electrolyte improves the wettability of the carbon anodes and lowers the tendency of the cells to depolarize (18). Thermoluminescent radiation dosimeters used in personnel and environmental monitoring and in radiation therapy contain lithium fluoride powder, extmded ribbons, or rods (19). 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

Lithium and other mood-stabilizing drugs require baseline and routine laboratory monitoring to help determine medical appropriateness for initiation of therapy and monitoring of potential adverse effects. Guidelines for such monitoring are outlined in Table 36-6. 

Lithium therapy necessitates the monitoring of thyroid function every 6-12 months in stabilised patients. Occurrence of symptoms such as lethargy, which may reflect hypothyroidism, should be monitored. 

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. 

The clinical value of monitoring drug therapy by measuring plasma levels is probably best exemplified by reference to lithium (F6). It is a useful drug, which has a narrow therapeutic index, and treatment without reference to plasma levels is probably not ethically justified. Toxic side effects are predictable and severe. It has an acceptably long plasma half-life, and its measurement both in blood and urine is comparatively simple. Moreover, there is no problem of interference from either active or inactive metabolites. 

Parameters to monitor Perform the following laboratory tests prior to and periodically during lithium therapy Serum creatinine complete blood count urinalysis sodium and potassium fasting glucose electrocardiogram and thyroid function tests. Check lithium serum levels twice weekly until dosage is stabilized. Once steady state has been reached, monitor the level weekly. Once the patient is on maintenance therapy, the level may be checked every 2 to 3 months. 

Therapy requires monitoring of lithium levels, thyroid, and renal function... 

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. 

The appearance of laboratory abnormalities does not require cessation of treatment however, if enzyme levels do not stabilize or return to normal, VPA should be discontinued and an alternate mood-stabilizing agent such as lithium used in its place. Liver function tests should be monitored more often during the first several weeks of therapy and every 6 to 12 months afterward. Routine liver function testing probably does not significantly prevent the occurrence of these unpredictable drug effects. Therefore, patients should be cautioned to immediately report symptoms of possible early hepatotoxicity such as easy bruising, decreased appetite, malaise, jaundice, and periorbital or dependent edema. In summary ... 

Serum lithium concentration should be monitored at the start of calcitonin therapy. 

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. 

Cardiovascular disease is not a contraindication to lithium, but the risks may be greater, in view of factors such as fluid and electrolyte imbalance and the use of concomitant medications. Close clinical and laboratory monitoring is necessary, and an alternative mood stabilizer may be preferred. While long-term tricyclic antidepressant therapy may be more cardiotoxic than lithium, the newer antidepressants (SSRIs and others) seem to be safe. 

In a cross-sectional study of 12 octogenarians (average age 84 years) who had taken lithium for an average of 54 months (mean serum concentration 0.42 mmol/1), none became toxic and none had to stop treatment because of adverse effects. Transient renal function abnormalities were noted one patient developed nephrogenic diabetes insipidus and one became hypothyroidic (510). For lithium therapy in very old people, the authors advised close monitoring in a specialized setting. 

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). 

Aronson JK, Reynolds DJM. ABC of monitoring drug therapy. Lithium. BMJ 1992 305 1273-6. 

BETA-BLOCKERS LITHIUM Report of episode of t lithium levels in elderly patient after starting low-dose propanolol. However, propanolol is often used to treat lithium-induced tremor without problems Mechanism uncertain at present, but propanolol seems to 1 lithium clearance Monitor lithium levels when starting propanolol therapy in elderly people... 

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. ... 

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