Toxicity with lithium

There is an additive bone marrow depression when methimazole or propylthiouracil is administered with otiier bone marrow depressants, such as the antineo-plastic drugs, or witii radiation therapy. When methimazole is administered with digitalis, there is an increased effectiveness of the digitalis and increased risk of toxicity. There is an additive effect of propylthiouracil when the drug is administered with lithium, potassium iodide, or sodium iodide When iodine products are administered with litiiium products, synergistic hypotiiyroid activity is likely to occur. 

The extensive clinical experience with these drugs in epilepsy shows they are better tolerated and less toxic than lithium (Bowden and Muller-Oerlinghausen, 2000 Rang et ah, 2003). Since the dose regimens for epilepsy and affective disorders are similar, it would be expected that the levels of adverse drug reactions would also be similar. With... 

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

Augmenting antidepressants with lithium has repeatedly been shown to be effective. But lithium is a difficult medication to take. It is very dangerous in overdose and can quickly reach toxic levels due to fluid loss from diarrhea, profuse sweating, or high fevers. Even at treatment levels, lithium can produce unpleasant side effects such as dizziness, frequent urination, and tremors. Despite all its problems, lithium... 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Increasing the dose of the current mood stabilizer deserves consideration when the medication level is at the lower end of the therapeutic range. This has the advantage of keeping the treatment simpler and less costly. However, as the dose is increased, the potential for intolerable side effects or toxicity (especially with lithium) becomes greater. 

The toxicity of lithium hydride differs markedly from that of the soluble salts of lithium because of its vigorous chemical reactivity with water, which produces acute irritation and corrosion of biological tissues. ... 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

Given the narrow margin between therapeutic and toxic plasma lithium levels, the physician must emphasize the prevention of lithium toxicity through adequate salt and water intake, especially during hot weather and exercise. Toxic lithium levels can cause severe neurotoxic reactions, with symptoms such as dysarthria, ataxia, and in-... 

Maintenance and prophylaxis with lithium, and perhaps other mood stabilizers, favorably alters the longitudinal course of a bipolar disorder. Thus, efforts to enhance long-term compliance are a necessary part of any overall strategy. The incidence of adverse or toxic events is relatively low, and close attention to the more clinically relevant consequences can usually prevent serious sequelae ( 198).An issue of critical importance for future research is the potential efficacy of alternative maintenance medication for those who fail to respond adequately to acute or long-term lithium therapy. 

CBZ s molecular structure is similar to imipramine. It is primarily metabolized by the liver and, like lithium, has a narrow therapeutic index, predisposing to toxicity with elevated serum levels. 

Other reported potentially significant drug interactions include the combination of verapamil or nifedipine with CBZ, which, at times, can lead to toxicity secondary to increases in CBZ levels, and neurotoxic reactions when verapamil or diltiazem is combined with lithium. 

Many adverse effects associated with lithium treatment occur at varying times after treatment is started. Some are harmless, but it is important to be alert to adverse effects that may signify impending serious toxic reactions. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Caution. Dimethylcadmium is not pyrophoric but, as is the case with cadmium dichloride, it is highly toxic. Methyliodide is highly toxic. Methyl-lithium is potentially pyrophoric. See general caution and safety section. 

Reports of hyperthyroidism associated with lithium include one in a woman who was also hypercalcemic with a normal parathyroid hormone (PTH) concentration (645) and two discovered while treating lithium toxicity (646). 

A 54-year old man, who had taken lithium for 15 years without problems, suddenly developed food and water aversion, hypercalcemia (2.75 mmol/1), and lithium toxicity, with a serum lithium concentration of 4.3 mmol/1 (677). He was confused, delirious, and irritable. Hemodialysis produced a marked improvement in laboratory tests, which became normal after 9 days. 

A major problem with lithium use is the danger of accumulation within the body.27 Lithium is not metabolized, and drug elimination takes place almost exclusively through excretion in the urine. Consequently, lithium has a tendency to accumulate in the body, and toxic levels can frequently be reached during administration. 

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. 

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