Lithium Intoxication Associated with Angiotensin II Type 1 Receptor Blockers in Women

Abstract

Lithium is like a two-edged sword; it is on the one hand a unique drug with psychoactive potential as a mood stabilizer and on the other hand a burdensome drug which can cause multisystem toxicity to alter basic cellular function. Many drugs interact with lithium, increasing its blood level. For example, elevated lithium concentrations after the initiation of angiotensin-converting enzyme (ACE) inhibitors have been well documented in literaturesHowever interaction between angiotensin II type 1 receptor (AT1R) blockers and lithium is rarely documented. We present a case of lithium intoxication after administration of telmisartan, an AT1R blocker, and examined reported cases of lithium intoxication by AT1R blockers. A 48-year old woman with a 30-year history of schizoaffective disorder was hospitalized for relapse due to poor compliance. After being given medications including lithium 1,200 mg/day, sodium valproate 400 mg/day, olanzapine 20 mg/day, levomepromazine 5 mg/day, and clonazepam 2mg/day, the patient's condition had been stable for a period of time. However the patient developed sustained hypertension (150-170/90-110 mmHg) about 2 months after the admission and was diagnosed with essential hypertension. Telmisartan 40 mg/day was prescribed to control blood pressure. At this time, routine examination revealed normal renal, liver and thyroid functions. The serum lithium concentration before the addition of telmisartan was 0.96-1.01 mEq/L for lithium 1,200 mg/day. Her blood pressure was gradually decreased to 120-130/ 70-90 mmHg by telmisartan. However the patient suddenly experienced slurred speech, unsteady gait, and confusion 24 days after the initiation of telmisartan. Laboratory results at this time were as follows: lithium concentration, 3.06 mEq/L; valproate concentration, 38 µg/mL; clonazepam concentration, 12.4 ng/mL; blood urine nitrogen, 24.0 mg/dL; creatinine, 1.87 mg/dL; sodium, 139 mEq/L; potassium, 3.6 mEq/L; and chloride, 101 mEq/L. The patient was diagnosed as having lithium intoxication with acute renal failure. All drugs were discontinued and the patient was sent to the emergency department of a general hospital to receive intensive care. The exact mechanism of lithium intoxication associated with AT1R blockers remains unclear, but it is supposed that natriuresis induced by AT1R blockers facilitate the retention of lithium from the kidney. Angiotensin II leads to stimulation of sodium reabsorption in the proximal tubules and secretion of aldosterone by the adrenal cortex. AT1R blockers might have resulted in decreasing sodium reabsorption in the proximal tubules and the decrease of aldosterone has a similar effect in distal tubules. Subsequently, the depletion of sodium might have in turn contributed to lithium reabsorption, eventually leading to lithium intoxicationTo our knowledge, there were seven case reports of lithium intoxication associated with AT1R blockers, including our case, and all of them were women shown in Table 1 [9]. Drug interaction between lithium and AT1R blockers migh...